U.S. patent application number 17/342292 was filed with the patent office on 2021-11-25 for bioelectric hydrogels and methods of manufacture and use.
The applicant listed for this patent is Vomaris Innovations, Inc.. Invention is credited to Joseph Del Rossi, Wendell King, Troy Paluszcyk.
Application Number | 20210361936 17/342292 |
Document ID | / |
Family ID | 1000005767305 |
Filed Date | 2021-11-25 |
United States Patent
Application |
20210361936 |
Kind Code |
A1 |
King; Wendell ; et
al. |
November 25, 2021 |
BIOELECTRIC HYDROGELS AND METHODS OF MANUFACTURE AND USE
Abstract
The present disclosure relates to a bioelectric hydrogel. In one
embodiment, a hydrogel comprises a hydrophilic polymer base and one
or more biocompatible electrodes configured to generate at least
one of a low level electric field (LLEF) or low level electric
current (LLEC). The hydrogel is configured to provide a
three-dimensional energy source within the hydrogel or to devises
proximate to the hydrogel.
Inventors: |
King; Wendell; (Pillager,
MN) ; Del Rossi; Joseph; (Tempe, AZ) ;
Paluszcyk; Troy; (Tempe, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Vomaris Innovations, Inc. |
Tempe |
AZ |
US |
|
|
Family ID: |
1000005767305 |
Appl. No.: |
17/342292 |
Filed: |
June 8, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15738413 |
Dec 20, 2017 |
11052244 |
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PCT/US2016/040827 |
Jul 1, 2016 |
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17342292 |
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62339500 |
May 20, 2016 |
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62187535 |
Jul 1, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/205 20130101;
A61N 1/0468 20130101; A61K 9/0009 20130101; A61N 1/0484 20130101;
A61L 31/145 20130101; A61N 1/303 20130101 |
International
Class: |
A61N 1/20 20060101
A61N001/20; A61N 1/04 20060101 A61N001/04; A61L 31/14 20060101
A61L031/14 |
Claims
1-11. (canceled)
12. A method for treating the skin, the method comprising: applying
a hydrogel comprising a hydrophilic polymer base and one or more
biocompatible electrodes configured to generate at least one of a
low level electric field (LLEF) or low level electric current
(LLEC) to an area where a injury is present or previously
occurred.
13. The method of claim 12, wherein the biocompatible electrodes
comprise a first bioelectric element comprising a first
microparticle formed from a first conductive material, and a second
bioelectric element comprising a second microparticle formed from a
second conductive material.
14. The method of claim 13, wherein the first conductive material
and the second conductive material comprise the same material.
15. The method of claim 13, wherein the first bioelectric element
and the second bioelectric element is a three dimensional matrix
capable of defining at least one voltaic cell for spontaneously
generating at least one electrical current with the conductive
material of the first bioelectric element when the first and second
bioelectric elements are introduced to an electrolytic
solution.
16. The method of claim 15, wherein the first bioelectric element
and the second bioelectric element each comprise a discrete
circuit.
17. The method of claim 16, further comprising a power source.
18. The method of claim 17, wherein the first bioelectric element
and the second bioelectric element spontaneously generate a
LLEF.
19. The method of claim 18, wherein the first bioelectric element
and the second bioelectric element spontaneously generate a LLEC
when contacted with an electrolytic solution.
20. The method of claim 19, wherein the LLEC provides a
microcurrent between 1 and 200 micro-amperes.
Description
FIELD
[0001] Biologic tissues and cells are affected by electrical
stimulus. Accordingly, apparatus and techniques for applying
electric stimulus to biological tissue and cells have been
developed to address a number of medical issues. The present
specification relates to bioelectric hydrogels and methods of
manufacture and use thereof.
SUMMARY
[0002] Disclosed and claimed herein are systems, devices, and
methods comprising at least one hydrogel. An embodiment comprises a
hydrogel, for example a conductive hydrogel, comprising a
hydrophilic polymer base and one or more biocompatible electrodes
comprising an array configured to generate at least one of a low
level electric field (LLEF) or low level electric current (LLEC).
The hydrogel can be of various viscosities to allow the hydrogel to
be shaped or molded into an object or formed to the human body such
as an arm, leg, torso, face, etc. Two arrays can be suspended in
hydrogels, for example in two hydrogels having different
properties, for example having different viscosities.
[0003] The biocompatible electrodes can comprise a first
bioelectric element comprising an array of a first microparticle
formed from a first conductive material, and a second bioelectric
element comprising an array of a second microparticle formed from a
second conductive material.
[0004] In embodiments, one of the arrays can comprise microcells or
electrodes embedded in or applied to a substrate, for example a
dressing.
[0005] Embodiments are directed toward methods for treating a
patient with the disclosed hydrogel systems and devices. Further
embodiments are directed toward methods for manufacturing a
disclosed system or device, comprising coupling a hydrogel
comprising a hydrophilic polymer base and one or more biocompatible
electrodes configured to generate at least one of a LLEF or LLEC to
an area where an injury is present.
[0006] Certain aspects utilize an external power source such as AC
or DC power, or pulsed RF. In one embodiment, the electrical energy
is derived from the dissimilar metals creating a battery at each
microcell/microcell or electrode/electrode interface, whereas those
embodiments with an external power source may require conductive
electrodes in a spaced apart configuration to predetermine the
electric field shape and strength.
[0007] Disclosed systems and devices can generate a localized
electric field in a pattern determined by the physical orientation
of the array or, for example, by the viscosity of the gel.
[0008] Disclosed herein are systems, devices, and methods for use
in treatment of subjects, for example around or about a muscle or
muscle group, for example the deltoids, the triceps, the biceps,
the quadriceps, the calf, the shoulder, the abdominals, the back,
or the like.
[0009] Disclosed embodiments can reduce or prevent muscle damage
(for example such as can occur during a workout or athletic
performance), improve muscle function, improve athletic
performance, and accelerate muscle recovery.
[0010] Disclosed herein are systems, devices, and methods for use
in treatment of subjects, for example treatment of tissue around or
about a joint of the body, for example the knee, the elbow, or the
like. Disclosed herein are systems, devices, and methods for use in
treatment of subjects, for example around the face, the neck, the
chest, the stomach, the arm, the back, the buttocks, the thigh, the
calf, the foot, or the like.
[0011] Further aspects include a method of directing cell migration
using a device disclosed herein. These aspects include methods of
improving re-epithelialization.
[0012] Further aspects include methods of increasing glucose uptake
as well as methods of increasing cellular thiol levels. Additional
aspects include a method of energizing mitochondria.
[0013] Further aspects include a method of stimulating cellular
protein expression.
[0014] Further aspects include a method of stimulating cellular DNA
synthesis.
[0015] Further aspects include a method of stimulating cellular
Ca.sup.2+ uptake.
[0016] Aspects of the invention include devices and methods for
increasing capillary density.
[0017] Embodiments include devices and methods for increasing
transcutaneous partial pressure of oxygen. Further embodiments
include methods and devices for treating or preventing pressure
ulcers.
[0018] In embodiments, these systems, devices, and methods can
increase cell migration, ATP production, and angiogenesis, thus
accelerating the healing process. Disclosed systems, devices, and
methods can also reduce bacterial population and/or proliferation
in and around injuries. The system, devices, and methods can also
increase cellular glucose uptake, thus increasing availability of
cellular energy and athletic performance.
[0019] Additional aspects include methods of preventing bacterial
biofilm formation. Aspects also include a method of reducing
microbial or bacterial proliferation, killing microbes or bacteria,
killing bacteria through a biofilm layer, or preventing the
formation of a biofilm. Embodiments include methods using devices
disclosed herein in combination with antibiotics for reducing
microbial or bacterial proliferation, killing microbes or bacteria,
killing bacteria through a biofilm layer, or preventing the
formation of a biofilm.
[0020] Further aspects include methods of treating diseases related
to metabolic deficiencies, such as diabetes, or other diseases
wherein the patient exhibits a compromised metabolic status.
[0021] Embodiments can also increase integrin expression and
accumulation in treatment areas.
[0022] Certain embodiments are designed for universal
conformability with any area of the body, for example a flat area
or a contoured area. In embodiments the systems, devices, and
methods include fabrics, for example clothing or dressings, that
comprise one or more biocompatible electrodes configured to
generate at least one of a low level electric field (LLEF) or low
level electric current (LLEC). In embodiments the dressings are
configured to conform to the area to be treated, for example by
producing the dressing in particular shapes including "slits" or
discontinuous regions. In embodiments the dressing can be produced
in a U shape wherein the "arms" of the U are substantially equal in
length as compared to the "base" of the U. In embodiments the
dressing can be produced in a U shape wherein the "arms" of the U
are substantially longer in length as compared to the "base" of the
U. In embodiments the dressing can be produced in a U shape wherein
the "arms" of the U are substantially shorter in length as compared
to the "base" of the U. In embodiments the dressing can be produced
in an X shape wherein the "arms" of the X are substantially equal
in length.
[0023] The systems and devices can comprise corresponding or
interlocking perimeter areas to assist the devices in maintaining
their position on the patient and/or their position relative to
each other. In certain embodiments, the systems and devices can
comprise a port or ports to provide access to the treatment area
beneath the device.
[0024] Certain embodiments can comprise a solution or formulation
comprising an active agent and a solvent or carrier or vehicle.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 depicts a graphical representation of a bioelectric
hydrogel according to one or more embodiments disclosed herein;
[0026] FIG. 2 depicts a three dimensional representation of a
bioelectric hydrogel according to one or more embodiments;
[0027] FIG. 3 depicts a graphical representation of the
microparticles within a bioelectric hydrogel according to one or
more embodiments;
[0028] FIGS. 4A, 4B, 4C, and 4D depict a alternative graphical
representation of a bioelectric hydrogel as a low viscosity
material according to one or more embodiments;
[0029] FIG. 5 depicts an alternative graphical representation of a
bioelectric hydrogel as a cell culture medium according to one or
more embodiments; and
[0030] FIGS. 6A and 6B depict alternative graphical representations
of a bioelectric hydrogel as a part of a garment.
[0031] FIG. 7 depicts an embodiment disclosed herein comprising a
zinc array embedded on a substrate and a gel comprising a silver
array.
[0032] FIGS. 8A, 8B, 8C, 8D, and 8E depict alternate embodiments
showing the location of discontinuous regions as well as anchor
regions of the system.
[0033] FIGS. 9A, 9B, 9C, and 9D depict alternate embodiments
showing a garment comprising a multi-array matrix of biocompatible
microcells.
[0034] FIG. 10 depicts a detailed plan view of a substrate layer
electrode pattern disclosed herein.
[0035] FIG. 11 depicts a detailed plan view of a substrate layer
electrode pattern as disclosed herein.
[0036] FIG. 12 depicts a detailed plan view of a substrate layer
electrode pattern disclosed herein;
[0037] FIG. 13 depicts a two-component system wherein two
hydrogels, each containing a separate electrode matrix, are
combined upon use.
DETAILED DESCRIPTION
[0038] Embodiments disclosed herein comprise systems and devices
that can provide a low level electric field (LLEF) to a tissue or
organism (thus a "LLEF system") or, when brought into contact with
an electrically conducting material, can provide a low level
electric microcurrent (LLEC) to a tissue or organism (thus a "LLEC
system"). Thus, in embodiments a LLEC system is a LLEF system that
is in contact with an electrically conducting material, for example
a liquid material. In certain embodiments, the micro-current or
electric field can be modulated, for example, to alter the
duration, size, shape, field depth, duration, current, polarity, or
voltage of the system. For example, it can be desirable to employ
an electric field of greater strength or depth in an area to
achieve optimal treatment. In embodiments the watt-density of the
system can be modulated.
Definitions
[0039] "Activation agent" as used herein means a composition useful
for maintaining a moist environment within and about the skin.
Activation agents can be in the form of gels or liquids. Activation
agents can be conductive. Activation gels can also be
antibacterial. In one embodiment, an activation agent can be a
liquid such as sweat or topical substance such as petroleum jelly
(for example with a conductive component added).
[0040] "Affixing" as used herein can mean contacting a patient or
tissue with a device or system disclosed herein. In embodiments
"affixing" can comprise the use of straps, elastic, etc.
[0041] "Antimicrobial agent" as used herein refers to an agent that
kills or inhibits the growth of microorganisms. One type of
antimicrobial agent can be an antibacterial agent. "Antibacterial
agent" or "antibacterial" as used herein refers to an agent that
interferes with the growth and reproduction of bacteria.
Antibacterial agents are used to disinfect surfaces and eliminate
potentially harmful bacteria. Unlike antibiotics, they are not used
as medicines for humans or animals, but are found in products such
as soaps, detergents, health and skincare products and household
cleaners. Antibacterial agents may be divided into two groups
according to their speed of action and residue production: The
first group contains those that act rapidly to destroy bacteria,
but quickly disappear (by evaporation or breakdown) and leave no
active residue behind (referred to as non-residue-producing).
Examples of this type are the alcohols, chlorine, peroxides, and
aldehydes. The second group consists mostly of newer compounds that
leave long-acting residues on the surface to be disinfected and
thus have a prolonged action (referred to as residue-producing).
Common examples of this group are triclosan, triclocarban, and
benzalkonium chloride. Another type of antimicrobial agent can be
an anti-fungal agent that can be used with the devices described
herein.
[0042] "Applied" or "apply" as used herein refers to contacting a
surface with a conductive material, for example printing, painting,
or spraying a conductive ink on a surface. Alternatively,
"applying" can mean contacting a patient or tissue or organism with
a device or system disclosed herein.
[0043] "Conductive material" as used herein refers to an object or
type of material which permits the flow of electric charges in one
or more directions. Conductive materials can comprise solids such
as metals or carbon, or liquids such as conductive metal solutions
and conductive gels. Conductive materials can be applied to form at
least one matrix. Conductive liquids can dry, cure, or harden after
application to form a solid material.
[0044] "Discontinuous region" as used herein refers to a "void" in
a material such as a hole, slot, or the like. The term can mean any
void in the material though typically the void is of a regular
shape. A void in the material can be entirely within the perimeter
of a material or it can extend to the perimeter of a material.
[0045] "Dots" as used herein refers to discrete deposits of
dissimilar reservoirs that can function as at least one battery
cell. The term can refer to a deposit of any suitable size or
shape, such as squares, circles, triangles, lines, etc. The term
can be used synonymously with, microcells, microspheres, etc.
"Microspheres" refers to are small spherical particles, with
diameters in the micrometer range (typically 1 .mu.m to 3000 .mu.m
(3 mm)). Microspheres are sometimes referred to as microparticles.
Microspheres can be manufactured from various natural and synthetic
materials. The term can be used synonymously with, microballoons,
beads, particles, etc.
[0046] "Electrode" refers to similar or dissimilar conductive
materials. In embodiments utilizing an external power source the
electrodes can comprise similar conductive materials.
[0047] In embodiments that do not use an external power source, the
electrodes can comprise dissimilar conductive materials that can
define an anode and a cathode.
[0048] "Expandable" as used herein refers to the ability to stretch
while retaining structural integrity and not tearing. The term can
refer to solid regions as well as discontinuous or void regions;
solid regions as well as void regions can stretch or expand.
[0049] "Galvanic cell" as used herein refers to an electrochemical
cell with a positive cell potential, which can allow chemical
energy to be converted into electrical energy. More particularly, a
galvanic cell can comprise a first reservoir serving as an anode
and a second, dissimilar reservoir serving as a cathode. Each
galvanic cell can store chemical potential energy. When a
conductive material is located proximate to a cell such that the
material can provide electrical and/or ionic communication between
the cell elements the chemical potential energy can be released as
electrical energy. Accordingly, each set of adjacent, dissimilar
reservoirs can function as a single-cell battery, and the
distribution of multiple sets of adjacent, dissimilar reservoirs
within the apparatus can function as a field of single-cell
batteries, which in the aggregate forms a multiple-cell battery
distributed across a surface. In embodiments utilizing an external
power source the galvanic cell can comprise electrodes connected to
an external power source, for example a battery or other power
source. In embodiments that are externally-powered, the electrodes
need not comprise dissimilar materials, as the external power
source can define the anode and cathode. In certain externally
powered embodiments, the power source need not be physically
connected to the device.
[0050] "Matrix" or "matrices" or "array" or "arrays" as used herein
refer to a pattern or patterns, such as those formed by electrodes
on a surface, such as a fabric or a fiber, or the like. Matrices
can also comprise a pattern or patterns within a solid or liquid
material or a three dimensional object. Matrices can be designed to
vary the electric field or electric current or microcurrent
generated. For example, the strength and shape of the field or
current or microcurrent can be altered, or the matrices can be
designed to produce an electric field(s) or current or microcurrent
of a desired strength or shape.
[0051] "Reduction-oxidation reaction" or "redox reaction" as used
herein refers to a reaction involving the transfer of one or more
electrons from a reducing agent to an oxidizing agent. The term
"reducing agent" can be defined in some embodiments as a reactant
in a redox reaction, which donates electrons to a reduced species.
A "reducing agent" is thereby oxidized in the reaction. The term
"oxidizing agent" can be defined in some embodiments as a reactant
in a redox reaction, which accepts electrons from the oxidized
species. An "oxidizing agent" is thereby reduced in the reaction.
In various embodiments a redox reaction produced between a first
and second reservoir provides a current between the dissimilar
reservoirs. The redox reactions can occur spontaneously when a
conductive material is brought in proximity to first and second
dissimilar reservoirs such that the conductive material provides a
medium for electrical communication and/or ionic communication
between the first and second dissimilar reservoirs. In other words,
in an embodiment electrical currents can be produced between first
and second dissimilar reservoirs without the use of an external
battery or other power source (e.g., a direct current (DC) such as
a battery or an alternating current (AC) power source such as a
typical electric outlet). Accordingly, in various embodiments a
system is provided which is "electrically self contained," and yet
the system can be activated to produce electrical currents. The
term "electrically self contained" can be defined in some
embodiments as being capable of producing electricity (e.g.,
producing currents) without an external battery or power source.
The term "activated" can be defined in some embodiments to refer to
the production of electric current through the application of a
radio signal of a given frequency or through ultrasound or through
electromagnetic induction. In other embodiments, a system can be
provided which comprises an external battery or power source. For
example, an AC power source can be of any wave form, such as a sine
wave, a triangular wave, or a square wave. AC power can also be of
any frequency such as for example 50 Hz or 60 HZ, or the like. AC
power can also be of any voltage, such as for example 120 volts, or
220 volts, or the like. In embodiments an AC power source can be
electronically modified, such as for example having the voltage
reduced, prior to use.
[0052] "Stretchable" as used herein refers to the ability of
embodiments that stretch without losing their structural integrity.
That is, embodiments can stretch to accommodate irregular skin
surfaces or surfaces wherein one portion of the surface can move
relative to another portion.
[0053] "Treatment" as used herein can include the use of disclosed
embodiments on muscles to prevent, reduce, or repair muscle damage.
Treatment can also include the use of disclosed embodiments on the
skin, eyes, etc. Treatment can include use on an injury, for
example a wound.
[0054] "Viscosity" as used herein refers to a measurement of a
fluid's resistance to gradual deformation by shear stress or
tensile stress. That is, embodiments can accommodate multiple
viscosity variations without losing structural integrity, wherein
one embodiment can be a liquid or a solid material.
[0055] LLEC/LLEF Systems, Devices, and Methods of Manufacture
[0056] Embodiments of the LLEC or LLEF system disclosed herein can
comprise electrodes or dots or microcells. Each electrode or dot or
microcell can be or comprise a conductive metal. In embodiments,
the electrodes or microcells can comprise any
electrically-conductive material, for example, an electrically
conductive hydrogel, metals, electrolytes, superconductors,
semiconductors, plasmas, and nonmetallic conductors such as
graphite and conductive polymers. Electrically conductive metals
can comprise silver, copper, gold, aluminum, molybdenum, zinc,
lithium, tungsten, brass, carbon, nickel, iron, palladium,
platinum, tin, bronze, carbon steel, lead, titanium, stainless
steel, mercury, Fe/Cr alloys, and the like. The electrode can be
solid, coated or plated with a different metal such as aluminum,
gold, platinum or silver.
[0057] In certain embodiments, reservoir or electrode geometry can
comprise circles, polygons, lines, zigzags, ovals, stars, or any
suitable variety of shapes. This provides the ability to
design/customize surface electric field shapes as well as depth of
penetration. For example. In embodiments it can be desirable to
employ an electric field of greater strength or depth in an area
where skin is thicker to achieve optimal treatment.
[0058] Reservoir or electrode or dot sizes and concentrations can
vary, as these variations can allow for changes in the properties
of the electric field created by embodiments of the invention.
Certain embodiments provide an electric field at about, for
example, 0.5-5.0 V at the device surface under normal tissue loads
with resistance of 100 to 100 K ohms.
[0059] In embodiments, systems and devices disclosed herein
comprise patterns of micro-batteries that create a field between
each dot pair. In embodiments, the unique field is very short, e.g.
in the range of physiologic electric fields. In embodiments, the
direction of the electric field produced by devices disclosed
herein is omnidirectional within a three dimensional material.
[0060] Embodiments disclosed herein can comprise patterns or
randomly dispersed microcells, for example within a hydrogel or on
a substrate. The patterns can be designed to produce an electric
field, an electric current, or both, over and through a three
dimensional material or tissue such as human skin. In embodiments
the pattern can be designed to produce a specific size, strength,
density, shape, or duration of electric field or electric current.
In embodiments reservoir or dot size and separation can be
altered.
[0061] In embodiments devices disclosed herein can apply an
electric field, an electric current, or both, wherein the field,
current, or both can be of varying size, strength, density, shape,
or duration in different areas of the embodiment. In embodiments,
by micro-sizing the electrodes or reservoirs, the shapes of the
electric field, electric current, or both can be customized,
increasing or decreasing very localized watt densities and allowing
for the design of patterns of electrodes or reservoirs wherein the
amount of electric field over a tissue can be designed or produced
or adjusted based upon feedback from the tissue or upon an
algorithm within sensors operably connected to the embodiment and a
control module. The electric field, electric current, or both can
be stronger in one zone and weaker in another. The electric field,
electric current, or both can change with time and be modulated
based on treatment goals or feedback from the tissue or patient.
The control module can monitor and adjust the size, strength,
density, shape, or duration of electric field or electric current
based on material parameters or tissue parameters. For example,
embodiments disclosed herein can produce and maintain very
localized electrical events. For example, embodiments disclosed
herein can produce specific values for the electric field duration,
electric field size, electric field shape, field depth, current,
polarity, and/or voltage of the device or system.
[0062] Devices disclosed herein can generate a localized electric
field in a pattern determined by the distance and physical
orientation of the cells or electrodes. Effective depth of the
electric field can be predetermined by the orientation and distance
between the cells or electrodes.
[0063] Embodiments can comprise a hydrogel. A hydrogel is a network
of polymer chains that are hydrophilic. Hydrogels are highly
absorbent natural or synthetic polymeric networks. Hydrogels can be
configured to contain a high percentage of water (e.g. they can
contain over 90% water). Hydrogels can possess a degree of
flexibility very similar to natural tissue, due to their
significant water content. A hydrogel can be configured in a
variety of viscosities. Viscosity is a measurement of a fluid or
material's resistance to gradual deformation by shear stress or
tensile stress. In embodiments the electrical field can be extended
through a semi-liquid hydrogel with a low viscosity such an
ointment or a cellular culture medium. In other embodiments the
electrical field can be extended through a solid hydrogel with a
high viscosity such as a Petri dish, clothing, or material used to
manufacture a prosthetic. In general, the hydrogel described herein
may be configured to a viscosity of between about 0.5 Pas and
greater than about 10.sup.12 Pas. In embodiments the viscosity of a
hydrogel can be, for example, between 0.5 and 10.sup.12 Pas,
between 1 Pas and 10.sup.6 Pas, between 5 and 10.sup.3 Pas, between
10 and 100 Pas, between 15 and 90 Pas, between 20 and 80 Pas,
between 25 and 70 Pas, between 30 and 60 Pas, or the like. In
embodiments, the hydrogel can comprise hydrophobic properties.
[0064] Dissimilar metals used to make a LLEC or LLEF system
disclosed herein can be silver and zinc. In certain embodiments the
electrodes are coupled with a non-conductive material to create a
random dot pattern or a uniform dot pattern within a hydrogel, most
preferably an array or multi-array of voltaic cells that do not
spontaneously react until they contact an electrolytic solution.
Sections of this description use the terms "coated," "plated," or
"printed" with "ink," but it is to be understood that a dot in a
hydrogel may also be a solid microsphere of conductive material.
The use of any suitable means for applying a conductive material is
contemplated. In embodiments "coated," "plated," or "printed" can
comprise any material such as a solution suitable for forming an
electrode on a surface of a microsphere such as a conductive
material comprising a conductive metal.
[0065] In another embodiment, microspheres can be formed, coated,
and plated by printing. In embodiments, printing devices can be
used to produce LLEC or LLEF systems disclosed herein. For example,
inkjet or "3D" printers can be used to produce embodiments. In
certain embodiments the binders or inks used to produce LLEC or
LLEF systems disclosed herein can comprise, for example, poly
cellulose inks, poly acrylic inks, poly urethane inks, silicone
inks, and the like. In embodiments the type of ink used can
determine the release rate of electrons from the reservoirs. In
embodiments various materials can be added to the ink or binder
such as, for example, conductive or resistive materials can be
added to alter the shape or strength of the electric field. Other
materials, such as silicon, can be added to enhance, for example,
scar reduction. Such materials can also be added to the spaces
between reservoirs.
[0066] FIG. 1 depicts a graphical representation of a bioelectric
hydrogel according to one or more embodiments. In FIG. 1, the
dissimilar first electrode 101 and second electrode 102 are in a
desired hydrophilic polymer base 103 of a hydrogel 100, for example
an ointment or cellular culture medium. In one embodiment a
hydrogel 100 is a material of a LLEC or LLEF system that comes into
direct contact with an area to be treated such as a skin surface or
within the hydrogel for cellular culture. Hydrogel 100 can also be
configured or shaped into a three dimensional object or material as
shown in FIG. 2. In FIG. 2, the dissimilar first electrode 201 and
second electrode 202 are coupled into a desired hydrophilic polymer
base 203 of a hydrogel 200. First electrode 201 and second
electrode 202 can be placed within hydrophilic polymer base 203 as
needed to accommodate the desired use.
[0067] In embodiments, systems and devices disclosed herein can
produce a low level electric current of between for example about 1
and about 200 micro-amperes, between about 10 and about 190
micro-amperes, between about 20 and about 180 micro-amperes,
between about 30 and about 170 micro-amperes, between about 40 and
about 160 micro-amperes, between about 50 and about 150
micro-amperes, between about 60 and about 140 micro-amperes,
between about 70 and about 130 micro-amperes, between about 80 and
about 120 micro-amperes, between about 90 and about 100
micro-amperes, between about 100 and about 150 micro-amperes,
between about 150 and about 200 micro-amperes, between about 200
and about 250 micro-amperes, between about 250 and about 300
micro-amperes, between about 300 and about 350 micro-amperes,
between about 350 and about 400 micro-amperes, between about 400
and about 450 micro-amperes, between about 450 and about 500
micro-amperes, between about 500 and about 550 micro-amperes,
between about 550 and about 600 micro-amperes, between about 600
and about 650 micro-amperes, between about 650 and about 700
micro-amperes, between about 700 and about 750 micro-amperes,
between about 750 and about 800 micro-amperes, between about 800
and about 850 micro-amperes, between about 850 and about 900
micro-amperes, between about 900 and about 950 micro-amperes,
between about 950 and about 1000 micro-amperes (1 milli-amp [mA]),
between about 1.0 and about 1.1 mA, between about 1.1 and about 1.2
mA, between about 1.2 and about 1.3 mA, between about 1.3 and about
1.4 mA, between about 1.4 and about 1.5 mA, between about 1.5 and
about 1.6 mA, between about 1.6 and about 1.7 mA, between about 1.7
and about 1.8 mA, between about 1.8 and about 1.9 mA, between about
1.9 and about 2.0 mA, between about 2.0 and about 2.1 mA, between
about 2.1 and about 2.2 mA, between about 2.2 and about 2.3 mA,
between about 2.3 and about 2.4 mA, between about 2.4 and about 2.5
mA, between about 2.5 and about 2.6 mA, between about 2.6 and about
2.7 mA, between about 2.7 and about 2.8 mA, between about 2.8 and
about 2.9 mA, between about 2.9 and about 3.0 mA, between about 3.0
and about 3.1 mA, between about 3.1 and about 3.2 mA, between about
3.2 and about 3.3 mA, between about 3.3 and about 3.4 mA, between
about 3.4 and about 3.5 mA, between about 3.5 and about 3.6 mA,
between about 3.6 and about 3.7 mA, between about 3.7 and about 3.8
mA, between about 3.8 and about 3.9 mA, between about 3.9 and about
4.0 mA, between about 4.0 and about 4.1 mA, between about 4.1 and
about 4.2 mA, between about 4.2 and about 4.3 mA, between about 4.3
and about 4.4 mA, between about 4.4 and about 4.5 mA, between about
4.5 and about 5.0 mA, between about 5.0 and about 5.5 mA, between
about 5.5 and about 6.0 mA, between about 6.0 and about 6.5 mA,
between about 6.5 and about 7.0 mA, between about 7.5 and about 8.0
mA, between about 8.0 and about 8.5 mA, between about 8.5 and about
9.0 mA, between about 9.0 and about 9.5 mA, between about 9.5 and
about 10.0 mA, between about 10.0 and about 10.5 mA, between about
10.5 and about 11.0 mA, between about 11.0 and about 11.5 mA,
between about 11.5 and about 12.0 mA, between about 12.0 and about
12.5 mA, between about 12.5 and about 13.0 mA, between about 13.0
and about 13.5 mA, between about 13.5 and about 14.0 mA, between
about 14.0 and about 14.5 mA, between about 14.5 and about 15.0 mA,
or the like.
[0068] In embodiments, systems and devices disclosed herein can
produce a low level electric current of between for example about 1
and about 400 micro-amperes, between about 20 and about 380
micro-amperes, between about 40 and about 360 micro-amperes,
between about 60 and about 340 micro-amperes, between about 80 and
about 320 micro-amperes, between about 100 and about 3000
micro-amperes, between about 120 and about 280 micro-amperes,
between about 140 and about 260 micro-amperes, between about 160
and about 240 micro-amperes, between about 180 and about 220
micro-amperes, or the like.
[0069] In embodiments, systems and devices disclosed herein can
produce a low level electric current of between for example about 1
micro-ampere and about 1 milli-ampere, between about 50 and about
800 micro-amperes, between about 200 and about 600 micro-amperes,
between about 400 and about 500 micro-amperes, or the like.
[0070] In embodiments, systems and devices disclosed herein can
produce a low level electric current of about 10 micro-amperes,
about 20 micro-amperes, about 30 micro-amperes, about 40
micro-amperes, about 50 micro-amperes, about 60 micro-amperes,
about 70 micro-amperes, about 80 micro-amperes, about 90
micro-amperes, about 100 micro-amperes, about 110 micro-amperes,
about 120 micro-amperes, about 130 micro-amperes, about 140
micro-amperes, about 150 micro-amperes, about 160 micro-amperes,
about 170 micro-amperes, about 180 micro-amperes, about 190
micro-amperes, about 200 micro-amperes, about 210 micro-amperes,
about 220 micro-amperes, about 240 micro-amperes, about 260
micro-amperes, about 280 micro-amperes, about 300 micro-amperes,
about 320 micro-amperes, about 340 micro-amperes, about 360
micro-amperes, about 380 micro-amperes, about 400 micro-amperes,
about 450 micro-amperes, about 500 micro-amperes, about 550
micro-amperes, about 600 micro-amperes, about 650 micro-amperes,
about 700 micro-amperes, about 750 micro-amperes, about 800
micro-amperes, about 850 micro-amperes, about 900 micro-amperes,
about 950 micro-amperes, about 1 milli-ampere, or the like.
[0071] In embodiments, the disclosed systems and devices can
produce a low level electric current of not more than about 10
micro-amperes, or not more than about 20 micro-amperes, not more
than about 30 micro-amperes, not more than about 40 micro-amperes,
not more than about 50 micro-amperes, not more than about 60
micro-amperes, not more than about 70 micro-amperes, not more than
about 80 micro-amperes, not more than about 90 micro-amperes, not
more than about 100 micro-amperes, not more than about 110
micro-amperes, not more than about 120 micro-amperes, not more than
about 130 micro-amperes, not more than about 140 micro-amperes, not
more than about 150 micro-amperes, not more than about 160
micro-amperes, not more than about 170 micro-amperes, not more than
about 180 micro-amperes, not more than about 190 micro-amperes, not
more than about 200 micro-amperes, not more than about 210
micro-amperes, not more than about 220 micro-amperes, not more than
about 230 micro-amperes, not more than about 240 micro-amperes, not
more than about 250 micro-amperes, not more than about 260
micro-amperes, not more than about 270 micro-amperes, not more than
about 280 micro-amperes, not more than about 290 micro-amperes, not
more than about 300 micro-amperes, not more than about 310
micro-amperes, not more than about 320 micro-amperes, not more than
about 340 micro-amperes, not more than about 360 micro-amperes, not
more than about 380 micro-amperes, not more than about 400
micro-amperes, not more than about 420 micro-amperes, not more than
about 440 micro-amperes, not more than about 460 micro-amperes, not
more than about 480 micro-amperes, not more than about 500
micro-amperes, not more than about 520 micro-amperes, not more than
about 540 micro-amperes, not more than about 560 micro-amperes, not
more than about 580 micro-amperes, not more than about 600
micro-amperes, not more than about 620 micro-amperes, not more than
about 640 micro-amperes, not more than about 660 micro-amperes, not
more than about 680 micro-amperes, not more than about 700
micro-amperes, not more than about 720 micro-amperes, not more than
about 740 micro-amperes, not more than about 760 micro-amperes, not
more than about 780 micro-amperes, not more than about 800
micro-amperes, not more than about 820 micro-amperes, not more than
about 840 micro-amperes, not more than about 860 micro-amperes, not
more than about 880 micro-amperes, not more than about 900
micro-amperes, not more than about 920 micro-amperes, not more than
about 940 micro-amperes, not more than about 960 micro-amperes, not
more than about 980 micro-amperes, or the like.
[0072] In embodiments, systems and devices disclosed herein can
produce a low level electric current of not less than 10
micro-amperes, not less than 20 micro-amperes, not less than 30
micro-amperes, not less than 40 micro-amperes, not less than 50
micro-amperes, not less than 60 micro-amperes, not less than 70
micro-amperes, not less than 80 micro-amperes, not less than 90
micro-amperes, not less than 100 micro-amperes, not less than 110
micro-amperes, not less than 120 micro-amperes, not less than 130
micro-amperes, not less than 140 micro-amperes, not less than 150
micro-amperes, not less than 160 micro-amperes, not less than 170
micro-amperes, not less than 180 micro-amperes, not less than 190
micro-amperes, not less than 200 micro-amperes, not less than 210
micro-amperes, not less than 220 micro-amperes, not less than 230
micro-amperes, not less than 240 micro-amperes, not less than 250
micro-amperes, not less than 260 micro-amperes, not less than 270
micro-amperes, not less than 280 micro-amperes, not less than 290
micro-amperes, not less than 300 micro-amperes, not less than 310
micro-amperes, not less than 320 micro-amperes, not less than 330
micro-amperes, not less than 340 micro-amperes, not less than 350
micro-amperes, not less than 360 micro-amperes, not less than 370
micro-amperes, not less than 380 micro-amperes, not less than 390
micro-amperes, not less than 400 micro-amperes, not less than about
420 micro-amperes, not less than about 440 micro-amperes, not less
than about 460 micro-amperes, not less than about 480
micro-amperes, not less than about 500 micro-amperes, not less than
about 520 micro-amperes, not less than about 540 micro-amperes, not
less than about 560 micro-amperes, not less than about 580
micro-amperes, not less than about 600 micro-amperes, not less than
about 620 micro-amperes, not less than about 640 micro-amperes, not
less than about 660 micro-amperes, not less than about 680
micro-amperes, not less than about 700 micro-amperes, not less than
about 720 micro-amperes, not less than about 740 micro-amperes, not
less than about 760 micro-amperes, not less than about 780
micro-amperes, not less than about 800 micro-amperes, not less than
about 820 micro-amperes, not less than about 840 micro-amperes, not
less than about 860 micro-amperes, not less than about 880
micro-amperes, not less than about 900 micro-amperes, not less than
about 920 micro-amperes, not less than about 940 micro-amperes, not
less than about 960 micro-amperes, not less than about 980
micro-amperes, or the like.
[0073] To maximize the number of voltaic cells, in various
embodiments, a "pattern" (in some hydrogels, the positions of the
electrodes can change) of alternating silver masses (e.g., 101 as
shown in FIG. 1) or electrodes or reservoirs and zinc masses (e.g.,
102 as shown in FIG. 1) or electrodes or reservoirs can create an
array of electrical currents across the hydrogel. A basic
embodiment, shown in FIG. 1, has each mass of silver randomly
spaced from masses of zinc, and has each mass of zinc randomly
spaced from masses of silver, according to an embodiment. In
another embodiment, mass of silver can be equally spaced from
masses of zinc, and has each mass of zinc equally spaced from
masses of silver. That is, the electrodes or reservoirs or dots can
either be a uniform pattern, a random pattern, or a combination of
the like. The first electrode 101 is separated from the second
electrode 102 by a hydrophilic polymer base 103. The designs of
first electrode 101 and second electrode 102 are simply round dots,
and in an embodiment, are repeated throughout the hydrogel. For an
exemplary device comprising silver and zinc, each silver design
preferably has about twice as much mass as each zinc design, in an
embodiment. For the embodiment in FIG. 1, the silver designs are
most preferably about a millimeter from each of the closest four
zinc designs, and vice-versa. The resulting pattern of dissimilar
metal masses defines an array of voltaic cells when introduced to
an electrolytic solution.
[0074] Because the spontaneous oxidation-reduction reaction of
silver and zinc uses a ratio of approximately two silver to one
zinc, the silver design can contain about twice as much mass as the
zinc design in an embodiment. At a spacing of about 1 mm between
the closest dissimilar metals (closest edge to closest edge) each
voltaic cell that contacts a conductive fluid such as a cosmetic
cream can create approximately 1 volt of potential that will
penetrate substantially through a hydrogel and its surrounding
surfaces. Closer spacing of the dots can decrease the resistance,
providing less potential, and the current will not penetrate as
deeply. If the spacing falls below about one tenth of a millimeter,
a benefit of the spontaneous reaction is that which is also present
with a direct reaction; silver can be electrically driven into the
skin. Therefore, spacing between the closest conductive materials
can be, for example, 1 .mu.m, 2 .mu.m, 3 .mu.m, 4 .mu.m, 5 .mu.m, 6
.mu.m, 7 .mu.m, 8 .mu.m, 9 .mu.m, 10 .mu.m, 11 .mu.m, 12 .mu.m, 13
.mu.m, 14 .mu.m, 15 .mu.m, 16 .mu.m, 17 .mu.m, 18 .mu.m, 19 .mu.m,
20 .mu.m, 21 .mu.m, 22 .mu.m, 23 .mu.m, 24 .mu.m, 25 .mu.m, 26
.mu.m, 27 .mu.m, 28 .mu.m, 29 .mu.m, 30 .mu.m, 31 .mu.m, 32 .mu.m,
33 .mu.m, 34 .mu.m, 35 .mu.m, 36 .mu.m, 37 .mu.m, 38 .mu.m, 39
.mu.m, 40 .mu.m, 41 .mu.m, 42 .mu.m, 43 .mu.m, 44 .mu.m, 45 .mu.m,
46 .mu.m, 47 .mu.m, 48 .mu.m, 49 .mu.m, 50 .mu.m, 51 .mu.m, 52
.mu.m, 53 .mu.m, 54 .mu.m, 55 .mu.m, 56 .mu.m, 57 .mu.m, 58 .mu.m,
59 .mu.m, 60 .mu.m, 61 .mu.m, 62 .mu.m, 63 .mu.m, 64 .mu.m, 65
.mu.m, 66 .mu.m, 67 .mu.m, 68 .mu.m, 69 .mu.m, 70 .mu.m, 71 .mu.m,
72 .mu.m, 73 .mu.m, 74 .mu.m, 75 .mu.m, 76 .mu.m, 77 .mu.m, 78
.mu.m, 79 .mu.m, 80 .mu.m, 81 .mu.m, 82 .mu.m, 83 .mu.m, 84 .mu.m,
85 .mu.m, 86 .mu.m, 87 .mu.m, 88 .mu.m, 89 .mu.m, 90 .mu.m, 91
.mu.m, 92 .mu.m, 93 .mu.m, 94 .mu.m, 95 .mu.m, 96 .mu.m, 97 .mu.m,
98 .mu.m, 99 .mu.m, 0.1 mm, or 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6
mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm,
1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2 mm, 2.1 mm, 2.2 mm, 2.3
mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm,
3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4
mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm,
4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7
mm, 5.8 mm, 5.9 mm, 6 mm, or the like.
[0075] In certain embodiments the spacing between the closest
conductive materials or electrodes or dots can be not more than 0.1
mm, or not more than 0.2 mm, not more than 0.3 mm, not more than
0.4 mm, not more than 0.5 mm, not more than 0.6 mm, not more than
0.7 mm, not more than 0.8 mm, not more than 0.9 mm, not more than 1
mm, not more than 1.1 mm, not more than 1.2 mm, not more than 1.3
mm, not more than 1.4 mm, not more than 1.5 mm, not more than 1.6
mm, not more than 1.7 mm, not more than 1.8 mm, not more than 1.9
mm, not more than 2 mm, not more than 2.1 mm, not more than 2.2 mm,
not more than 2.3 mm, not more than 2.4 mm, not more than 2.5 mm,
not more than 2.6 mm, not more than 2.7 mm, not more than 2.8 mm,
not more than 2.9 mm, not more than 3 mm, not more than 3.1 mm, not
more than 3.2 mm, not more than 3.3 mm, not more than 3.4 mm, not
more than 3.5 mm, not more than 3.6 mm, not more than 3.7 mm, not
more than 3.8 mm, not more than 3.9 mm, not more than 4 mm, not
more than 4.1 mm, not more than 4.2 mm, not more than 4.3 mm, not
more than 4.4 mm, not more than 4.5 mm, not more than 4.6 mm, not
more than 4.7 mm, not more than 4.8 mm, not more than 4.9 mm, not
more than 5 mm, not more than 5.1 mm, not more than 5.2 mm, not
more than 5.3 mm, not more than 5.4 mm, not more than 5.5 mm, not
more than 5.6 mm, not more than 5.7 mm, not more than 5.8 mm, not
more than 5.9 mm, not more than 6 mm, or the like.
[0076] In certain embodiments spacing between the closest
conductive materials or electrodes or dots can be not less than 0.1
mm, not less than 0.2 mm, not less than 0.3 mm, not less than 0.4
mm, not less than 0.5 mm, not less than 0.6 mm, not less than 0.7
mm, not less than 0.8 mm, not less than 0.9 mm, not less than 1 mm,
not less than 1.1 mm, not less than 1.2 mm, not less than 1.3 mm,
not less than 1.4 mm, not less than 1.5 mm, not less than 1.6 mm,
not less than 1.7 mm, not less than 1.8 mm, not less than 1.9 mm,
not less than 2 mm, not less than 2.1 mm, not less than 2.2 mm, not
less than 2.3 mm, not less than 2.4 mm, not less than 2.5 mm, not
less than 2.6 mm, not less than 2.7 mm, not less than 2.8 mm, not
less than 2.9 mm, not less than 3 mm, not less than 3.1 mm, not
less than 3.2 mm, not less than 3.3 mm, not less than 3.4 mm, not
less than 3.5 mm, not less than 3.6 mm, not less than 3.7 mm, not
less than 3.8 mm, not less than 3.9 mm, not less than 4 mm, not
less than 4.1 mm, not less than 4.2 mm, not less than 4.3 mm, not
less than 4.4 mm, not less than 4.5 mm, not less than 4.6 mm, not
less than 4.7 mm, not less than 4.8 mm, not less than 4.9 mm, not
less than 5 mm, not less than 5.1 mm, not less than 5.2 mm, not
less than 5.3 mm, not less than 5.4 mm, not less than 5.5 mm, not
less than 5.6 mm, not less than 5.7 mm, not less than 5.8 mm, not
less than 5.9 mm, not less than 6 mm, or the like.
[0077] Disclosures of the present specification comprise LLEC or
LLEF systems comprising a hydrophilic polymer base and a first
electrode design formed from a first conductive liquid that
comprises a mixture of a polymer and a first element, the first
conductive liquid being applied into a position of contact with the
primary surface, the first element comprising a metal species, and
the first electrode design comprising at least one dot or
reservoir, wherein selective ones of the at least one dot or
reservoir have approximately a 1.5 .mu.m+/-1 .mu.m mean diameter; a
second electrode design formed from a second conductive liquid that
comprises a mixture of a polymer and a second element, the second
element comprising a different metal species than the first
element, the second conductive liquid being printed into a position
of contact with the primary surface, and the second electrode
design comprising at least one other dot or reservoir, wherein
selective ones of the at least one other dot or reservoir have
approximately a 2 .mu.m+1-2 .mu.m mean diameter; a spacing on the
primary surface that is between the first electrode design and the
second electrode design such that the first electrode design does
not physically contact the second electrode design, wherein the
spacing is approximately 1.5 .mu.m+1-1 .mu.m, and at least one
repetition of the first electrode design and the second electrode
design, the at least one repetition of the first electrode design
being substantially adjacent the second electrode design, wherein
the at least one repetition of the first electrode design and the
second electrode design, in conjunction with the spacing between
the first electrode design and the second electrode design, defines
at least one pattern of at least one voltaic cell for spontaneously
generating at least one electrical current when introduced to an
electrolytic solution. Therefore, electrodes, dots or reservoirs
can have a mean diameter of 0.2 .mu.m, 0.3 .mu.m, 0.4 .mu.m, 0.5
.mu.m, 0.6 .mu.m, 0.7 .mu.m, 0.8 .mu.m, 0.9 .mu.m, 1.0 .mu.m, 1.1
.mu.m, 1.2 .mu.m, 1.3 .mu.m, 1.4 .mu.m, 1.5 .mu.m, 1.6 .mu.m, 1.7
.mu.m, 1.8 .mu.m, 1.9 .mu.m, 2.0 .mu.m, 2.1 .mu.m, 2.2 .mu.m, 2.3
.mu.m, 2.4 .mu.m, 2.5 .mu.m, 2.6 .mu.m, 2.7 .mu.m, 2.8 .mu.m, 2.9
.mu.m, 3.0 .mu.m, 3.1 .mu.m, 3.2 .mu.m, 3.3 .mu.m, 3.4 .mu.m, 3.5
.mu.m, 3.6 .mu.m, 3.7 .mu.m, 3.8 .mu.m, 3.9 .mu.m, 4.0 .mu.m, 4.1
.mu.m, 4.2 .mu.m, 4.3 .mu.m, 4.4 .mu.m, 4.5 .mu.m, 4.6 .mu.m, 4.7
.mu.m, 4.8 .mu.m, 4.9 .mu.m, 5.0 .mu.m, or the like not exceeding 1
mm.
[0078] In further embodiments, electrodes, dots or reservoirs can
have a mean diameter of not less than 0.2 .mu.m, or not less than
0.3 .mu.m, not less than 0.4 .mu.m, not less than 0.5 .mu.m, not
less than 0.6 .mu.m, not less than 0.7 .mu.m, not less than 0.8
.mu.m, not less than 0.9 .mu.m, not less than 1.0 .mu.m, not less
than 1.1 .mu.m, not less than 1.2 .mu.m, not less than 1.3 .mu.m,
not less than 1.4 .mu.m, not less than 1.5 .mu.m, not less than 1.6
.mu.m, not less than 1.7 .mu.m, not less than 1.8 .mu.m, not less
than 1.9 .mu.m, not less than 2.0 .mu.m, not less than 2.1 .mu.m,
not less than 2.2 .mu.m, not less than 2.3 .mu.m, not less than 2.4
.mu.m, not less than 2.5 .mu.m, not less than 2.6 .mu.m, not less
than 2.7 .mu.m, not less than 2.8 .mu.m, not less than 2.9 .mu.m,
not less than 3.0 .mu.m, not less than 3.1 .mu.m, not less than 3.2
.mu.m, not less than 3.3 .mu.m, not less than 3.4 .mu.m, not less
than 3.5 .mu.m, not less than 3.6 .mu.m, not less than 3.7 .mu.m,
not less than 3.8 .mu.m, not less than 3.9 .mu.m, not less than 4.0
.mu.m, not less than 4.1 .mu.m, not less than 4.2 .mu.m, not less
than 4.3 .mu.m, not less than 4.4 .mu.m, not less than 4.5 .mu.m,
not less than 4.6 .mu.m, not less than 4.7 .mu.m, not less than 4.8
.mu.m, not less than 4.9 .mu.m, not less than 5.0 .mu.m, or the
like not exceeding 1 mm.
[0079] In further embodiments, electrodes, dots or reservoirs can
have a mean diameter of not more than 0.2 .mu.m, or not more than
0.3 .mu.m, not more than 0.4 .mu.m, not more than 0.5 .mu.m, not
more than 0.6 .mu.m, not more than 0.7 .mu.m, not more than 0.8
.mu.m, not more than 0.9 .mu.m, not more than 1.0 .mu.m, not more
than 1.1 .mu.m, not more than 1.2 .mu.m, not more than 1.3 .mu.m,
not more than 1.4 .mu.m, not more than 1.5 .mu.m, not more than 1.6
.mu.m, not more than 1.7 .mu.m, not more than 1.8 .mu.m, not more
than 1.9 .mu.m, not more than 2.0 .mu.m, not more than 2.1 .mu.m,
not more than 2.2 .mu.m, not more than 2.3 .mu.m, not more than 2.4
.mu.m, not more than 2.5 .mu.m, not more than 2.6 .mu.m, not more
than 2.7 .mu.m, not more than 2.8 .mu.m, not more than 2.9 .mu.m,
not more than 3.0 .mu.m, not more than 3.1 .mu.m, not more than 3.2
.mu.m, not more than 3.3 .mu.m, not more than 3.4 .mu.m, not more
than 3.5 .mu.m, not more than 3.6 .mu.m, not more than 3.7 .mu.m,
not more than 3.8 .mu.m, not more than 3.9 .mu.m, not more than 4.0
.mu.m, not more than 4.1 .mu.m, not more than 4.2 .mu.m, not more
than 4.3 .mu.m, not more than 4.4 .mu.m, not more than 4.5 .mu.m,
not more than 4.6 .mu.m, not more than 4.7 .mu.m, not more than 4.8
.mu.m, not more than 4.9 .mu.m, not more than 5.0 .mu.m, or the
like.
[0080] Disclosures of the present specification include LLEC or
LLEF systems comprising a primary surface of a material wherein the
material is adapted to be applied to an area of tissue such as a
muscle; and a first electrode design formed from a first conductive
liquid that includes a mixture of a polymer and a first element,
the first conductive liquid being applied into a position of
contact with the primary surface, the first element including a
metal species, and the first electrode design including at least
one dot or reservoir, wherein selective ones of the at least one
dot or reservoir have approximately a 1.5 mm+1-1 mm mean
diameter.
[0081] In embodiments, electrodes, dots or reservoirs can have a
mean diameter of 0.2 mm, or 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm,
0.8 mm, 0.9 mm, 1.0 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6
mm, 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm,
2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3.0 mm, 3.1 mm, 3.2 mm, 3.3
mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4.0 mm, 4.1 mm,
4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5.0
mm, or the like.
[0082] In further embodiments, electrodes, dots or reservoirs can
have a mean diameter of not less than 0.2 mm, or not less than 0.3
mm, not less than 0.4 mm, not less than 0.5 mm, not less than 0.6
mm, not less than 0.7 mm, not less than 0.8 mm, not less than 0.9
mm, not less than 1.0 mm, not less than 1.1 mm, not less than 1.2
mm, not less than 1.3 mm, not less than 1.4 mm, not less than 1.5
mm, not less than 1.6 mm, not less than 1.7 mm, not less than 1.8
mm, not less than 1.9 mm, not less than 2.0 mm, not less than 2.1
mm, not less than 2.2 mm, not less than 2.3 mm, not less than 2.4
mm, not less than 2.5 mm, not less than 2.6 mm, not less than 2.7
mm, not less than 2.8 mm, not less than 2.9 mm, not less than 3.0
mm, not less than 3.1 mm, not less than 3.2 mm, not less than 3.3
mm, not less than 3.4 mm, not less than 3.5 mm, not less than 3.6
mm, not less than 3.7 mm, not less than 3.8 mm, not less than 3.9
mm, not less than 4.0 mm, not less than 4.1 mm, not less than 4.2
mm, not less than 4.3 mm, not less than 4.4 mm, not less than 4.5
mm, not less than 4.6 mm, not less than 4.7 mm, not less than 4.8
mm, not less than 4.9 mm, not less than 5.0 mm, or the like.
[0083] In further embodiments, electrodes, dots or reservoirs can
have a mean diameter of not more than 0.2 mm, or not more than 0.3
mm, not more than 0.4 mm, not more than 0.5 mm, not more than 0.6
mm, not more than 0.7 mm, not more than 0.8 mm, not more than 0.9
mm, not more than 1.0 mm, not more than 1.1 mm, not more than 1.2
mm, not more than 1.3 mm, not more than 1.4 mm, not more than 1.5
mm, not more than 1.6 mm, not more than 1.7 mm, not more than 1.8
mm, not more than 1.9 mm, not more than 2.0 mm, not more than 2.1
mm, not more than 2.2 mm, not more than 2.3 mm, not more than 2.4
mm, not more than 2.5 mm, not more than 2.6 mm, not more than 2.7
mm, not more than 2.8 mm, not more than 2.9 mm, not more than 3.0
mm, not more than 3.1 mm, not more than 3.2 mm, not more than 3.3
mm, not more than 3.4 mm, not more than 3.5 mm, not more than 3.6
mm, not more than 3.7 mm, not more than 3.8 mm, not more than 3.9
mm, not more than 4.0 mm, not more than 4.1 mm, not more than 4.2
mm, not more than 4.3 mm, not more than 4.4 mm, not more than 4.5
mm, not more than 4.6 mm, not more than 4.7 mm, not more than 4.8
mm, not more than 4.9 mm, not more than 5.0 mm, or the like.
[0084] The material concentrations or quantities within and/or the
relative sizes (e.g., dimensions or surface area) of the reservoirs
or dots or electrodes can be selected deliberately to achieve
various characteristics of the systems' behavior. For example, the
quantities of material within a reservoir can be selected to
provide an apparatus having an operational behavior that depletes
at approximately a desired rate and/or that "dies" after an
approximate period of time after activation. In an embodiment the
reservoirs are configured to sustain one or more currents for an
approximate pre-determined period of time, after activation. It is
to be understood that the amount of time that currents are
sustained can depend on external conditions and factors (e.g., the
quantity and type of activation material), and currents can occur
intermittently depending on the presence or absence of activation
material. Further disclosure relating to producing reservoirs that
are configured to sustain one or more currents for an approximate
pre-determined period of time can be found in U.S. Pat. No.
7,904,147 entitled SUBSTANTIALLY PLANAR ARTICLE AND METHODS OF
MANUFACTURE issued Mar. 8, 2011, which is incorporated by reference
herein in its entirety.
[0085] In various embodiments the difference of the standard
potentials of the first and second reservoirs or electrodes or dots
can be in a range from about 0.05 V to approximately 5.0 V. For
example, the standard potential can be 0.05 V, 0.06 V, 0.07 V, 0.08
V, 0.09 V, 0.1 V, 0.2 V, 0.3 V, 0.4 V, 0.5 V, 0.6 V, 0.7 V, 0.8 V,
0.9 V, 1.0 V, 1.1 V, 1.2 V, 1.3 V, 1.4 V, 1.5 V, 1.6 V, 1.7 V, 1.8
V, 1.9 V, 2.0 V, 2.1 V, 2.2 V, 2.3 V, 2.4 V, 2.5 V, 2.6 V, 2.7 V,
2.8 V, 2.9 V, 3.0 V, 3.1 V, 3.2 V, 3.3 V, 3.4 V, 3.5 V, 3.6 V, 3.7
V, 3.8 V, 3.9 V, 4.0 V, 4.1 V, 4.2 V, 4.3 V, 4.4 V, 4.5 V, 4.6 V,
4.7 V, 4.8 V, 4.9 V, 5.0 V, or the like.
[0086] In a particular embodiment, the difference between the
standard potentials of the first and second reservoirs or
electrodes or dots can be at least 0.05 V, at least 0.06 V, at
least 0.07 V, at least 0.08 V, at least 0.09 V, at least 0.1 V, at
least 0.2 V, at least 0.3 V, at least 0.4 V, at least 0.5 V, at
least 0.6 V, at least 0.7 V, at least 0.8 V, at least 0.9 V, at
least 1.0 V, at least 1.1 V, at least 1.2 V, at least 1.3 V, at
least 1.4 V, at least 1.5 V, at least 1.6 V, at least 1.7 V, at
least 1.8 V, at least 1.9 V, at least 2.0 V, at least 2.1 V, at
least 2.2 V, at least 2.3 V, at least 2.4 V, at least 2.5 V, at
least 2.6 V, at least 2.7 V, at least 2.8 V, at least 2.9 V, at
least 3.0 V, at least 3.1 V, at least 3.2 V, at least 3.3 V, at
least 3.4 V, at least 3.5 V, at least 3.6 V, at least 3.7 V, at
least 3.8 V, at least 3.9 V, at least 4.0 V, at least 4.1 V, at
least 4.2 V, at least 4.3 V, at least 4.4 V, at least 4.5 V, at
least 4.6 V, at least 4.7 V, at least 4.8 V, at least 4.9 V, at
least 5.0 V, or the like.
[0087] In a particular embodiment, the difference of the standard
potentials of the first and second reservoirs or electrodes or dots
can be not more than 0.05 V, or not more than 0.06 V, not more than
0.07 V, not more than 0.08 V, not more than 0.09 V, not more than
0.1 V, not more than 0.2 V, not more than 0.3 V, not more than 0.4
V, not more than 0.5 V, not more than 0.6 V, not more than 0.7 V,
not more than 0.8 V, not more than 0.9 V, not more than 1.0 V, not
more than 1.1 V, not more than 1.2 V, not more than 1.3 V, not more
than 1.4 V, not more than 1.5 V, not more than 1.6 V, not more than
1.7 V, not more than 1.8 V, not more than 1.9 V, not more than 2.0
V, not more than 2.1 V, not more than 2.2 V, not more than 2.3 V,
not more than 2.4 V, not more than 2.5 V, not more than 2.6 V, not
more than 2.7 V, not more than 2.8 V, not more than 2.9 V, not more
than 3.0 V, not more than 3.1 V, not more than 3.2 V, not more than
3.3 V, not more than 3.4 V, not more than 3.5 V, not more than 3.6
V, not more than 3.7 V, not more than 3.8 V, not more than 3.9 V,
not more than 4.0 V, not more than 4.1 V, not more than 4.2 V, not
more than 4.3 V, not more than 4.4 V, not more than 4.5 V, not more
than 4.6 V, not more than 4.7 V, not more than 4.8 V, not more than
4.9 V, not more than 5.0 V, or the like. In embodiments that
include very small reservoirs (e.g., on the nanometer scale), the
difference of the standard potentials can be substantially less or
more. The electrons that pass between the first reservoir and the
second reservoir can be generated as a result of the difference of
the standard potentials. Further disclosure relating to standard
potentials can be found in U.S. Pat. No. 8,224,439 entitled
BATTERIES AND METHODS OF MANUFACTURE AND USE issued Jul. 17, 2012,
which is incorporated be reference herein in its entirety.
[0088] FIG. 3 depicts a graphical representation of a microparticle
or microsphere of a bioelectric hydrogel according to one or more
embodiments. Hydrogel 300 comprises a dissimilar first electrode
301 and a second electrode 302 that are coupled into a desired
hydrophilic polymer base 303 of a hydrogel. Prior to coupling the
electrodes or dots to the hydrophilic polymer base, the
microspheres can be coated, plated, or printed with a conductive
material or ink using a biocompatible binder mixed with each of the
dissimilar metals that will create voltaic cells. Most inks are
simply a carrier, and a binder mixed with pigment. Similarly,
conductive metal solutions can be a binder mixed with a conductive
element. The resulting conductive metal solutions can be used with
an application method to apply the conductive material to the
microspheres in predetermined thickness or depth. For example,
microsphere 350 can be coated with a conductive metal 351 while
leaving the interior 352 of the microsphere unchanged. In another
embodiment, microsphere can be completely formed by a conductive
material 361 with no unchanged interior 352 of the microsphere.
Once the conductive metal solutions dry and/or cure, the conductive
material can substantially maintain their relative position on a
microsphere, even in a flexible material such as a hydrogel used
for a LLEC or LLEF system. The conductive metal solution applied to
the microspheres can be allowed to dry before being applied to a
hydrophilic polymer base so that the conductive materials do not
mix within a hydrogel, which could interrupt the array and cause
direct reactions that will release the elements.
[0089] Embodiments can include systems and devices in the form of a
two-component gel that is mixed on use. For example, in embodiments
disclosed devices can comprise a first electrode material suspended
in a hydrogel, and a second electrode material suspended in a
separate hydrogel (in a separate reservoir). The hydrogels can then
be mixed on use, thus activating the material. FIG. 13 demonstrates
an exemplary embodiment. Reservoir 130 comprising a first electrode
material and reservoir 135 comprising a second electrode material
are mixed 137 when the material is applied. Upon mixing, the
material is activated and produces current.
[0090] In certain embodiments, disclosed systems and devices can
comprise a first electrode material and a second electrode material
in a single gel. The individual electrodes or dots can be isolated,
for example with a time, temperature, or pH-dependent membrane or
barrier or coating. For example, the membrane can be designed to
degrade, thus exposing the electrodes to each other, after a set
period of time, or at a desired temperature, or at a desired pH.
For example, the membrane can be designed to degrade at body
temperature, for example at human body temperature. In embodiments
the membrane can be designed to degrade upon mechanical stress, for
example upon application. In certain embodiments, for example
treatment methods, it can be preferable to utilize AC or DC
current. For example, embodiments disclosed herein can employ
phased array, pulsed, square wave, sinusoidal, or other wave forms,
combinations, or the like. Certain embodiments utilize a controller
to produce and control power production and/or distribution to the
device.
[0091] Embodiments can comprise coatings on the surface or within
the hydrogel, such as, for example, over or between the electrodes
or cells or an excipient or activation agent suspended within the
coating. Coatings can comprise, for example, silicone, and
electrolytic mixture, hypoallergenic agents, drugs, biologics, stem
cells, skin substitutes, cosmetic products, combinations, or the
like. Drugs suitable for use with embodiments of the invention
comprise analgesics, antibiotics, anti-inflammatories, or the
like.
[0092] In embodiments the material can comprise a port to access
the interior of the material, for example to add fluid, gel,
cosmetic products, a hydrating material, or some other material.
Certain embodiments can comprise a "blister" top that can enclose a
material such as an antibacterial. In embodiments the blister top
can contain a material that is released into or on to the material
when the blister is pressed, for example a liquid or cream. For
example, embodiments disclosed herein can comprise a blister top
containing an antibacterial or the like.
[0093] A system or device disclosed herein and placed over tissue
such as skin can move relative to the tissue. Reducing the amount
of motion between tissue and device can be advantageous to
treatment. Slotting or placing cuts into the device can result in
less friction or tension on the skin. In embodiments, use of an
elastic dressing similar to the elasticity of the skin is also
possible.
[0094] In embodiments the system comprises a component such as
elastic or other such fabric to maintain or help maintain its
position. In embodiments the system comprises components such as
straps to maintain or help maintain its position. In certain
embodiments the system or device comprises a strap on either end of
the long axis, or a strap linking on end of the long axis to the
other. In embodiments that straps can comprise Velcro or a similar
fastening system. In embodiments the straps can comprise elastic
materials. In embodiments the hydrogel can be configured into
straps as a part of the material.
[0095] In further embodiments the strap can comprise a conductive
material, for example a wire to electrically link the device with
other components, such as monitoring equipment or a power source.
In embodiments the device can be wirelessly linked to monitoring or
data collection equipment, for example linked via Bluetooth to a
cell phone or computer that collects data from the device. In
certain embodiments the device can comprise data collection means,
such as temperature, pH, pressure, or conductivity data collection
means. In certain embodiments, disclosed devices and systems can
comprise data collection means, such as temperature, pH, pressure,
or conductivity data collection means. Embodiments can comprise a
display, for example to visually present, for example, the
temperature, pH, pressure, or conductivity data to a user.
Embodiments can include, for example, tracking equipment so as to
track and/or quantify a user's movements or performance.
Embodiments can include, for example, an accelerometer, so as to
measure impact forces on a user.
[0096] In embodiments the system comprises a component such as an
adhesive to maintain or help maintain its position. The adhesive
component can be covered with a protective layer that is removed to
expose the adhesive at the time of use. In embodiments the adhesive
can comprise, for example, sealants, such as hypoallergenic
sealants, gecko sealants, mussel sealants, waterproof sealants such
as epoxies, and the like. Straps can comprise Velcro or similar
materials to aid in maintaining the position of the device.
[0097] In embodiments the positioning component can comprise an
elastic film with an elasticity, for example, similar to that of
skin, or greater than that of skin, or less than that of skin. In
embodiments, the LLEC or LLEF system can comprise a laminate where
layers of the laminate can be of varying elasticities. For example,
an outer layer may be highly elastic and an inner layer in-elastic
or less elastic. The in-elastic layer can be made to stretch by
placing stress relieving discontinuous regions through the
thickness of the material so there is a mechanical displacement
rather than stress that would break the hydrogel before stretching
would occur. In embodiments the stress relieving discontinuous
regions can extend completely through a layer or the system or can
be placed where expansion is required. In embodiments of the system
the stress relieving discontinuous regions do not extend all the
way through the system or a portion of the system such as the
substrate. In embodiments the discontinuous regions can pass
halfway through the long axis of the substrate.
[0098] In certain embodiments, a substrate comprising an array can
comprise one layer of a composite dressing, for example a composite
garment or fabric comprising the substrate, an adhesive layer, an
expandable absorbent layer, and a stretchable, expandable film
layer. The expandable absorbent layer can absorb excess fluid from
the substrate and expand away from the treatment area, thus
preventing oversaturation of the treatment area with resultant
maceration and increased infection risk. The stretchable,
expandable film layer can stretch to accommodate a larger foam
volume as the foam absorbs liquid. This aspect reduces shear forces
on the skin. Additionally, the vertically-expanding foam and film
allows the dressing to absorb more volume of fluid in a smaller
contact area.
[0099] In embodiments the device or substrate can be shaped to fit
an area of desired use, for example the human face, or around a
subject's eyes, or around a subject's forehead, a subject's cheeks,
a subject's chin, a subject's back, a subject's chest, a subject's
legs, a subject's ankle, a subject's arms, a subject's wound or any
area where treatment is desired. For example, in embodiments the
device can be shaped to fit an area where an injury has occurred,
such as a patient's legs where there are abrasions from a bicycle
accident or a patient's arm where tissue is surgically removed to
treat a medical condition. In certain embodiments the device can be
shaped to fit an area where an injury previously occurred to
prevent reoccurrence of the injury. In other embodiments the device
can be shaped to fit and area where increased cellular energy is
needed such as the quadriceps in ones legs while running.
[0100] Embodiments disclosed herein comprise biocompatible
electrodes or reservoirs or dots within a hydrogel, for example an
ointment, a cell culture medium, or the like. In embodiments the
hydrogel can be configured into a variety of shapes, for example to
better follow the contours of an area to be treated, such as the
face or back. In embodiments the hydrogel can be configured into a
gauze or mesh or plastic.
[0101] Embodiments disclosed herein can comprise a hydrogel and a
substrate. Suitable substrates for use in embodiments disclosed
herein can be absorbent or non-absorbent textiles, low-adhesives,
vapor permeable films, hydrocolloids, hydrogels, alginates, foams,
foam-based materials, cellulose-based materials comprising
Kettenbach fibers, hollow tubes, fibrous materials, such as those
impregnated with anhydrous/hygroscopic materials, beads and the
like, or any suitable material as known in the art. In embodiments
the material can form, for example, a mask, such as that worn on
the body, a pant, a glove, a sock, a shirt or a portion thereof,
for example an elastic or compression shirt, or a portion thereof,
a wrapping, towel, cloth, fabric, or the like. In other embodiment
the hydrogel can be configured into multi layer embodiments from a
variation of the described above.
[0102] In embodiments the substrate layer can be non-pliable, for
example, a plastic such as a pad (for example a shoulder or thigh
pad) or a helmet interior or the like.
[0103] A LLEC or LLEF system disclosed herein can comprise "anchor"
regions or "arms" or straps to affix the system securely. The
anchor regions or arms can anchor the LLEC or LLEF system. For
example, a LLEC or LLEF system can be secured to an area proximal
to a joint or irregular skin surface, and anchor regions of the
system can extend to areas of minimal stress or movement to
securely affix the system. Further, the LLEC system can reduce
stress on an area, for example by "countering" the physical stress
caused by movement.
[0104] In embodiments the LLEC or LLEF system can comprise
additional materials to aid in treatment.
[0105] In embodiments, the LLEC or LLEF system can comprise
instructions or directions on how to place the system to maximize
its performance. Embodiments comprise a kit comprising an LLEC or
LLEF system and directions for its use.
[0106] In certain embodiments dissimilar metals can be used to
create an electric field with a desired voltage. In certain
embodiments the pattern of reservoirs can control the watt density
and shape of the electric field.
[0107] In certain embodiments dissimilar metals can be used to
create an electric field with a desired voltage within the
hydrogel. In certain embodiments the pattern of reservoirs can
control the watt density and shape of the electric field.
[0108] Certain embodiments can utilize a power source to create the
electric current, such as a battery or a micro-battery. The power
source can be any energy source capable of generating a current in
the LLEC system and can comprise, for example, AC power, DC power,
radio frequencies (RF) such as pulsed RF, induction, ultrasound,
and the like.
[0109] Similarly, electrodes or reservoirs or dots can adhere or
bond to a substrate through use of a biocompatible binder.
Conductive metal solutions can comprise a binder mixed with a
conductive element. The resulting conductive metal solution can be
used with an application method such as screen printing to apply
the electrodes to the primary surface in predetermined patterns.
Once the conductive metal solution dries and/or cures, the patterns
of spaced electrodes can substantially maintain their relative
position, even on a flexible material such as that used for a LLEC
or LLEF system. The conductive metal solution can be allowed to dry
before being applied to a surface.
[0110] In another embodiment, the reservoirs or dots or electrodes
are configured to be same specific gravity as the hydrophilic
polymer base of the hydrogel. This embodiment, allows the
reservoirs or dots to be suspended in the hydrogel for a desired
used without the reservoirs or dots being pulled to the bottom of
the hydrogels due to other factors such as gravity. In particular,
the reservoirs or dots will not settle and the hydrogel can be
manufactured and stored for extended periods of time.
[0111] In certain embodiments that utilize a poly-cellulose binder,
the binder itself can have a beneficial effect such as reducing the
local concentration of matrix metallo-proteases through an
iontophoretic process that drives the cellulose into the
surrounding tissue. This process can be used to electronically
drive other components such as drugs into the surrounding
tissue.
[0112] The binder can comprise any biocompatible liquid material
that can be mixed with a conductive element (preferably metallic
crystals of silver or zinc) to create a conductive solution which
can be applied as a thin coating to a microsphere. One suitable
binder is a solvent reducible polymer, such as the polyacrylic
non-toxic silk-screen ink manufactured by COLORCON.RTM. Inc., a
division of Berwind Pharmaceutical Services, Inc. (see
COLORCON.RTM. NO-TOX.RTM. product line, part number NT28). In an
embodiment the binder is mixed with high purity (at least 99.999%)
metallic silver crystals to make the silver conductive solution.
The silver crystals, which can be made by grinding silver into a
powder, are preferably smaller than 100 microns in size or about as
fine as flour. In an embodiment, the size of the crystals is about
325 mesh, which is typically about 40 microns in size or a little
smaller. The binder is separately mixed with high purity (at least
99.99%, in an embodiment) metallic zinc powder which has also
preferably been sifted through standard 325 mesh screen, to make
the zinc conductive solution. For better quality control and more
consistent results, most of the crystals used should be larger than
325 mesh and smaller than 200 mesh. For example the crystals used
should be between 200 mesh and 325 mesh, or between 210 mesh and
310 mesh, between 220 mesh and 300 mesh, between 230 mesh and 290
mesh, between 240 mesh and 280 mesh, between 250 mesh and 270 mesh,
between 255 mesh and 265 mesh, or the like.
[0113] Other powders of metal can be used to make other conductive
metal solutions in the same way as described in other
embodiments.
[0114] The size of the metal crystals, the availability of the
surface to the conductive fluid and the ratio of metal to binder
affects the release rate of the metal from the mixture. When
COLORCON.RTM. polyacrylic ink is used as the binder, about 10 to 40
percent of the mixture should be metal for a long term bandage (for
example, one that stays on for about 10 days). In embodiments, the
percent of the mixture that should be metal can be 8 percent, 10
percent, 12 percent, 14 percent, 16 percent, 18 percent, 20
percent, 22 percent, 24 percent, 26 percent, 28 percent, 30
percent, 32 percent, 34 percent, 36 percent, 38 percent, 40
percent, 42 percent, 44 percent, 46 percent, 48 percent, 50
percent, or the like.
[0115] If the same binder is used, but the percentage of the
mixture that is metal is increased to 60 percent or higher, a
typical system will be effective for longer. For example, for a
longer term device, the percent of the mixture that should be metal
can be 40 percent, 42 percent, 44 percent, 46 percent, 48 percent,
50 percent, 52 percent, 54 percent, 56 percent, 58 percent, 60
percent, 62 percent, 64 percent, 66 percent, 68 percent, 70
percent, 72 percent, 74 percent, 76 percent, 78 percent, 80
percent, 82 percent, 84 percent, 86 percent, 88 percent, 90
percent, or the like.
[0116] For LLEC or LLEF systems comprising a pliable substrate it
can be desired to decrease the percentage of metal down to 5
percent or less, or to use a binder that causes the crystals to be
more deeply embedded, so that the primary surface will be
antimicrobial for a very long period of time and will not wear
prematurely. Other binders can dissolve or otherwise break down
faster or slower than a polyacrylic ink, so adjustments can be made
to achieve the desired rate of spontaneous reactions from the
voltaic cells.
[0117] The voltage present at the site of treatment or within the
hydrogel is typically in the range of millivolts but disclosed
embodiments can introduce a much higher voltage, for example near 1
volt when using the 1 mm spacing of dissimilar metals already
described. The higher voltage is believed to drive the current
deeper into the treatment area or within the hydrogel. In this way
the current not only can drive silver and zinc into the treatment
if desired for treatment, but the current can also provide a
stimulatory current so that the entire surface area can be treated.
The higher voltage may also increase antimicrobial effect bacteria
and preventing biofilms. The electric field can also have
beneficial effects on cell migration, ATP production, and
angiogenesis.
[0118] Embodiments disclosed herein relating to tissue treatment
can also comprise selecting a patient or tissue in need of, or that
could benefit by, using a bioelectric hydrogel.
[0119] While various embodiments have been shown and described, it
will be realized that alterations and modifications can be made
thereto without departing from the scope of the following claims.
It is expected that other methods of applying the conductive
material can be substituted as appropriate. Also, there are
numerous shapes, sizes and patterns of voltaic cells that have not
been described but it is expected that this disclosure will enable
those skilled in the art to incorporate their own designs which
will then be applied to a hydrogel to create voltaic cells which
will become active when brought into contact with an electrolytic
solution.
[0120] Certain embodiments comprise LLEC or LLEF systems comprising
embodiments designed to be used on irregular, non-planar, or
"stretching" surfaces. Embodiments disclosed herein can be used
with numerous irregular surfaces of the body, comprising the face,
the shoulder, the elbow, the wrist, the finger joints, the hip, the
knee, the ankle, the toe joints, decubitus wound, diabetic ulcer
etc. Additional embodiments disclosed herein can be used in areas
where tissue is prone to movement, for example the eyelid, the ear,
the lips, the nose, the shoulders, the back, etc.
[0121] In certain embodiments, the hydrogel or substrate can be
shaped to fit a particular region of the body such as an arm, leg,
ankle, chest, decubitus wound, or diabetic ulcer. Additionally, a
hydrogel can be shaped to form objects such as petri dishes,
prosthetics, or clothing. In various embodiments the hydrogel can
have a low viscosity or a high viscosity while forming to such
objects or regions of the body.
[0122] FIGS. 4A-4C depict an alternative graphical representation
of a bioelectric hydrogel as a low viscosity material according to
one or more embodiments. In FIGS. 4A and 4B, bandage 400 can
accommodate a hydrogel with a low viscosity such as an ointment.
Bandage 400 comprises affixing element 405 and a dressing element
407. Hydrogel 406 comprises first reservoir or dots 401 and second
reservoir or dots 402 coupled to hydrophilic polymer base 403.
Hydrogel 406 can be a low viscosity to be applied to dressing
element 407 of bandage 400. After application of hydrogel 406,
bandage 400 can be then affixed to form to a body part such as hand
450 (as shown in FIG. 4C). In another embodiment, hydrogel 406 can
be applied or formed directly to a body part without bandage 400.
In another embodiment, hydrogel 406 can also be form to tissue
within a wound. In particular, a low viscosity hydrogel can be
packed into a wound such a decubitus wound, diabetic ulcer, or the
like to directly contact the damaged tissue for treatment or
healing. Finally, a hydrogel can be formulated to produce a current
and voltage that exactly matched the current of injury produced
when an injury of the body occurs.
[0123] FIG. 5 depicts an alternative graphical representation of a
bioelectric hydrogel as a cell culture medium according to one or
more embodiments. Hydrogels can also be configured as a cellular
culture medium. For example, Petri dish 500 can comprise a hydrogel
510 cellular medium. Hydrogel 510 comprises first reservoir or dots
501 and second reservoir or dots 502 coupled to hydrophilic polymer
base 503. Hydrogel 510 within Petri dish 500 can be a low viscosity
such as a serum free medium or a high viscosity such as an agarose
gel. In embodiments the viscosity of hydrogel 510 can be configured
to accommodate distinct cellular growth. For example, neuro cells
505 and nerve ganglions are very difficult to grow in vitro. The
first reservoir 501 and second reservoir 502 coupled to hydrophilic
polymer base 503 in the hydrogel 510 creates a three dimensional
energy source which can aid in the cellular culture of neuro cells
505 and nerve ganglions in vitro. In another embodiment, nutrients
can be added to hydrogel 510 to facilitate growth and maintain life
of neuro cells 505 and nerve ganglions in vitro. In another
embodiment, a hydrogel can be formed or shaped into a Petri dish
500. In particular, hydrogel can be configured to be a high
viscosity to be molded into a Petri dish for cellular culture. In
this embodiment, electrical stimuli will be directed into the
culture medium from the solid structure of the Petri dish.
[0124] FIG. 6 depicts an alternative graphical representation of a
bioelectric hydrogel as a high viscosity material according to one
or more embodiments. In FIG. 6, a garment 600 can be shaped or
formed from a high viscosity hydrogel. For example, garment 600 can
be entirely a solid hydrogel or be woven into hydrogel thread to be
used in the manufacturing of such garments. A high viscosity
hydrogel also comprises a plurality of reservoirs 601 or dots
coupled to a hydrophilic polymer base 602. Reservoirs or dots 601
can provide a LLEF to tissue, when brought in contact with an
activating agent, such as sweat. In another embodiment, dots 601
can be configured to a portion of the garment 600 and 610. For
example, dots 601 within hydrogel can be applied to only to the
lower back of garment 610 to provide LLEF only to the lower back.
In certain embodiment, dots 601 within hydrogel can also be removed
and a new set of dots 601 can be applied to similar or new location
on garment (600 & 610).
[0125] FIG. 7 depicts a multi-phase embodiment utilizing a silver
hydrogel phase and a zinc substrate phase.
[0126] FIGS. 8A-8E depict alternate embodiments showing the
location of discontinuous regions as well as anchor regions of a
substrate.
[0127] FIGS. 9A-9D depict an example garment 900 comprising a
multi-array matrix of biocompatible microcells. Garment 900
comprises electrodes 901 and substrate 902. Electrodes 901 are
printed around the entirety of substrate 902 including the back of
garment 910. Electrodes 901 can provide a LLEF to tissue, and, when
in contact with a conductive material, a LLEC. In another
embodiment, electrodes 901 can be printed to a portion of the
garment 950, as depicted in FIG. 9B. For example, electrodes 901
can be applied to only the back of garment 960 to provide LLEF to
lower back. In certain embodiment, electrodes 901 can also be
removed and a new set of dots 901 can be applied to similar or new
location on garment (950 & 960). The array can be printed or
applied such that it contacts the skin while in use. For example,
the array can be printed on or applied to the inside of the
garment.
[0128] FIG. 10 shows an embodiment utilizing two electrodes on a
substrate. Upper arms 140 and 145 can be, for example, 1, 2, 3, or
4 mm in width. Lower arm 147 and serpentine 149 can be, for
example, 1, 2, 3, or 4 mm in width. The electrodes can be, for
example, 1, 2, or 3 mm in depth.
[0129] FIG. 11 shows an embodiment utilizing two electrodes on a
substrate. Upper arms 150 and 155 can be, for example, 1, 2, 3, or
4 mm in width. The extensions protruding from the lower arm 156 can
be, for example, 1, 1.5, 2, 2.5, 3, 3.5, or 4 mm in width. The
extensions protruding from the comb 158 can be, for example, 1, 2,
3, 4, 5, 6, or 7 mm in width. The electrodes can be, for example,
1, 2, or 3 mm in depth.
[0130] FIG. 12 shows an embodiment utilizing two electrodes on a
substrate. Upper arms 160 and 165 can be, for example, 1, 2, 3, or
4 mm in width. Lower block 167 can be, for example, 30, 32, 34, 36,
38, 40, 42, 44, 46, 48, 50, 52, or 54 mm along its shorter axis.
Lower block 167 can be, for example, 60, 65, 70, 75, 80, 85, 90,
95, or 100 mm along its longer axis. The electrodes can be, for
example, 1, 2, or 3 mm in depth.
[0131] In embodiments such as those in FIGS. 10-12, the width and
depth of the various areas of the electrode can be designed to
produce a particular electric field, or, when both electrodes are
in contact with a conductive material, a particular electric
current. For example, the width of the various areas of the
electrode can be, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5
mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm, 1.3 mm,
1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2 mm, 2.1 mm, 2.2
mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm,
3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9
mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm,
4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6
mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, or 7 mm, or 8 mm, or 9 mm, or 10
mm, or 11 mm, or the like.
[0132] In embodiments, the depth or thickness of the various areas
of the electrode can be, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4
mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm,
1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2 mm, 2.1
mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm,
3 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8
mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm,
4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5
mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, or the like.
[0133] The shortest distance between the two electrodes in an
embodiment can be, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5
mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm, 1.3 mm,
1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2 mm, 2.1 mm, 2.2
mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm,
3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9
mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm,
4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6
mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm,
12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21
mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm,
31 mm, 32 mm, 33 mm, 34 mm, or the like.
[0134] In embodiments, the length of the long axis of the electrode
can be, for example, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm,
2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4
mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm,
4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1
mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm,
6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm,
16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25
mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33 mm, 34 mm,
35 mm, 36 mm, 37 mm, 38 mm, 39 mm, 40 mm, 41 mm, 42 mm, 43 mm, 44
mm, 45 mm, 46 mm, 47 mm, 48 mm, 49 mm, 50 mm, 75 mm, 100 mm, 150
mm, 200 mm, 250 mm, 300 mm, 350 mm, 400 mm, 450 mm, 500 mm, 600 mm,
700 mm, 800 mm, 900 mm, 1000 mm, or more, or the like.
[0135] In embodiments, the length of the short axis of the
electrode can be, for example, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4
mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm, 3.2 mm,
3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1
mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm,
5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8
mm, 5.9 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14
mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm,
24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33
mm, 34 mm, 35 mm, 36 mm, 37 mm, 38 mm, 39 mm, 40 mm, 41 mm, 42 mm,
43 mm, 44 mm, 45 mm, 46 mm, 47 mm, 48 mm, 49 mm, 50 mm, 75 mm, 100
mm, or more, or the like.
[0136] Certain embodiments disclosed herein comprise a method of
manufacturing a hydrogel LLEC or LLEF system, the method comprising
coupling a hydrophilic polymer base with one or more biocompatible
electrodes configured to generate at least one of a low level
electric field (LLEF) or low level electric current (LLEC). In
another embodiment, the method comprises joining with a hydrophilic
polymer base with one or more biocompatible electrodes comprising a
first bioelectric element comprising a first microparticle formed
from a first conductive material, and a second bioelectric element
comprising a second microparticle formed from a second conductive
material. First microparticle formed from a first conductive
material is a reducing agent. Second microparticle formed from a
second conductive material is an oxidizing agent. In embodiments
the hydrogel can be configured to be a low or high viscosity.
[0137] Embodiments disclosed herein comprise LLEC and LLEF systems
that can produce an electrical stimulus and/or can electromotivate,
electroconduct, electroinduct, electrotransport, and/or
electrophorese one or more therapeutic materials in areas of target
tissue (e.g., iontophoresis), and/or can cause one or more biologic
or other materials in proximity to, on or within target tissue to
be rejuvenated.
[0138] LLEC/LLEF Systems, Devices, and Methods of Use
[0139] Embodiments disclosed herein include LLEC and LLEF systems
that can produce an electrical stimulus and/or can electromotivate,
electroconduct, electroinduct, electrotransport, and/or
electrophorese one or more therapeutic materials in areas of target
tissue (e.g., iontophoresis), and/or can cause one or more biologic
or other materials in proximity to, on or within target tissue to
be rejuvenated. Further disclosure relating to materials that can
produce an electrical stimulus can be found in U.S. Pat. No.
7,662,176 entitled FOOTWEAR APPARATUS AND METHODS OF MANUFACTURE
AND USE issued Feb. 16, 2010, which is incorporated herein by
reference in its entirety.
[0140] Treatment of Wounds
[0141] The wound healing process includes several phases, including
an inflammatory phase and a proliferative phase. The proliferative
phase involves cell migration (such as by human keratinocytes)
wherein cells migrate into the wound site and cell proliferation
wherein the cells reproduce. This phase also involves angiogenesis
and the growth of granulation tissue. During cell migration, many
epithelial cells have the ability to detect electric fields and
respond with directed migration. Their response typically requires
Ca.sup.2+ influx, the presence of specific growth factors such as
Integrin and intracellular kinase activity. Most types of cells
migrate directionally in a small electric field, a phenomenon
called galvanotaxis or electrotaxis. Electric fields of strength
equal to those detected at wound edges direct cell migration and
can override some other well-accepted coexistent guidance cues such
as contact inhibition. Aspects of the present specification
disclose in part a method of treating an individual with a wound.
Treating a wound can include covering the wound with a LLMC or LLEF
system. Embodiments disclosed herein can promote wound healing by
directing cell migration during the wound healing process.
[0142] In embodiments a wound can be an acute or chronic wound, a
diabetic wound of the lower extremities, such as of the legs or
feet, a post-radiation tissue injury, crush injuries or compartment
syndrome and other acute traumatic ischemic wounds, venous stasis
or arterial-insufficiency ulcers, compromised grafts and flaps,
infected wounds, pressure ulcers, necrotizing soft-tissue
infections, burns, cancer-related wounds, osteomyelitis, surgical
wounds, traumatic wounds, insect bites, and the like. In an
embodiment a wound can be a non-penetrating wound, such as the
result of blunt trauma or friction with other surfaces. Typically
this type of wound does not break through the skin and may include
an abrasion (scraping of the outer skin layer), a laceration (a
tear-like wound), a contusion (swollen bruises due to accumulation
of blood and dead cells under skin), or the like. In other
embodiments a wound can be a penetrating wound. These result from
trauma that breaks through the full thickness of skin and include
stab wounds (trauma from sharp objects, such as knives), skin cuts,
surgical wounds (intentional cuts in the skin to perform surgical
procedures), shrapnel wounds (wounds resulting from exploding
shells), or gunshot wounds (wounds resulting from firearms). In
further embodiments a wound can be a thermal wound such as
resulting from heat or cold, a chemical wound such as resulting
from an acid or base, an electrical wound, or the like.
[0143] Chronic wounds often do not heal in normal stages, and the
wounds can also fail to heal in a timely fashion. LLMC and LLEF
systems disclosed herein can promote the healing of chronic wounds
by increasing cell migration, cell proliferation, and/or cell
signaling. Increased migration can be seen in various cell types,
such as for example keratinocytes.
[0144] In embodiments, treating the wound can comprise applying a
LLMC or LLEF system to the wound such that the system can stretch
with movement of the wound and surrounding area. In certain
embodiments, the system can be stretched before application to the
wound such that the wound management system "pulls" the wound edges
together.
[0145] In embodiments, methods for treating or dressing a wound
comprises the step of topically administering an additional
material on the wound surface or upon the matrix of biocompatible
microcells. These additional materials can comprise, for example,
activation gels, rhPDGF (REGRANEX.RTM.), Vibronectin:IGF complexes,
CELLSPRAY.RTM., RECELL.RTM., INTEGRA.RTM. dermal regeneration
template, BIOMEND.RTM., INFUSE.RTM., ALLODERM.RTM., CYMETRA.RTM.,
SEPRAPACK.RTM., SEPRAMESH.RTM., SKINTEMP.RTM., MEDFIL.RTM.,
COSMODERM.RTM., COSMOPLAST.RTM., OP-1.RTM., ISOLAGEN.RTM.,
CARTICEL.RTM., APLIGRAF.RTM., DERMAGRAFT.RTM., TRANSCYTE.RTM.,
ORCEL.RTM., EPICEL.RTM., and the like. In embodiments the
activation gel can be, for example, TEGADERM.RTM. 91110 by 3M,
Molnlycke Normlgel 0.9% Sodium chloride, HISPAGEL.RTM.,
LUBRIGEL.RTM., or other compositions useful for maintaining a moist
environment about the wound or useful for healing a wound via
another mechanism.
[0146] Aspects of the present specification provide, in part,
methods of reducing a symptom associated with a wound. In an aspect
of this embodiment the symptom reduced is edema, hyperemia,
erythema, bruising, tenderness, stiffness, swollenness, fever, a
chill, a breathing problem, fluid retention, a blood clot, a loss
of appetite, an increased heart rate, a formation of granulomas,
fibrinous, pus, or non-viscous serous fluid, a formation of an
ulcer, or pain.
[0147] Treating a wound can refer to reducing the size of, or
preventing an increase in size of a wound. For example, treating
can reduce the width of a wound by, e.g., at least 20%, at least
25%, at least 30%, at least 35%, at least 40%, at least 45%, at
least 50%, at least 55%, at least 60%, at least 65%, at least 70%,
at least 75%, at least 80%, at least 85%, at least 90% at least
95%, or at least 100%.
[0148] Treating a wound can refer to reducing the depth of, or
preventing an increase in depth of a wound. For example, treating
can reduce the depth of a wound by, e.g., at least 20%, at least
25%, at least 30%, at least 35%, at least 40%, at least 45%, at
least 50%, at least 55%, at least 60%, at least 65%, at least 70%,
at least 75%, at least 80%, at least 85%, at least 90% at least
95%, or at least 100%.
[0149] Treatment of Bites
[0150] Systems disclosed herein can be used to treat animal bites,
for example snake bites. A LLMC or LLEF system can be applied to
the bite(s) or bitten area, wherein the low level micro-current or
electric field can neutralize the immune reaction to the bites or
the venom, or neutralize the antigens present in such bites and
thus reduce pain and itching. In embodiments the systems and
devices disclosed herein can treat venomous bites by altering the
function of venoms, such as, for example, protein-based venoms.
[0151] Systems disclosed herein can be used to treat insect bites,
for example mosquito bites. A LLMC or LLEF system can be applied to
the bite(s) or bitten area, wherein the low level micro-current or
electric field can neutralize the immune reaction to the bites or
any venom and thus reduce pain and itching.
[0152] Treatment of Microbial Infection
[0153] Embodiments of the disclosed LLMC and LLEF systems can
provide microbicidal activity. For example, embodiments disclosed
herein can prevent, limit, or reduce formation of biofilms by
interfering with bacterial signaling. Further embodiments can kill
bacteria through an established biofilm.
[0154] Aspects disclosed herein include systems, devices, and
methods for treating parasitic infections. For example, methods
disclosed herein include treatments for ectoparasitic infections
caused by, for example, Sarcoptes scabiei (causes scabies),
Pediculus humanus capitis (causes head lice), Phthirus pubis
(causes pubic lice), Leishmania (causes leishmaniasis), and the
like. Leishmaniasis is a highly focal disease with widely scattered
foci. The parasite may survive for decades in asymptomatic infected
people, who are of great importance for the transmission since they
can spread visceral leishmaniasis indirectly through the sandflies.
The parasites can also be transmitted directly from person to
person through the sharing of infected needles which is often the
case with the Leishmania/HIV co-infection. Cutaneous leishmaniasis
is the most common form, which causes a sore at the bite site,
which heals in a few months to a year, leaving an
unpleasant-looking scar. Systems disclosed herein can be used to
treat cutaneous leishmaniasis in the initial infection stage as
well as the latent stage or in the active disfiguring lesions
resulting from the infection.
[0155] Cellular Activation
[0156] Embodiments of the disclosed LLMC and LLEF systems can
increase cell migration by applying an electric current or electric
field or both to a treatment area. For example, the systems can
increase migration of human keratinocytes. The systems can also be
used to promote re-epithelialization for example in a wound.
[0157] Embodiments of the disclosed LLMC and LLEF systems can
increase glucose uptake in target tissues and cells, for example by
applying a LLEF system disclosed herein to a treatment area where
increased uptake of glucose is desired. In embodiments glucose
uptake can be increased to energize mitochondria.
[0158] Embodiments of the disclosed LLMC and LLEF systems can
increase cell signaling in target tissues and cells, for example by
applying a LLEF system disclosed herein to a treatment area where
increased cell signaling is desired.
[0159] Embodiments of the disclosed LLMC and LLEF systems can
create hydrogen peroxide in target tissues and cells, for example
by applying a LLEF system disclosed herein to a treatment area
where hydrogen peroxide production is desired.
[0160] Treatment of Disease
[0161] Embodiments of the disclosed LLMC and LLEF systems can be
used to treat disease. For example, embodiments can be used to
increase glucose uptake thus reducing serum glucose levels and
treating diseases relating to increased glucose levels, such as
diabetes. Increasing cellular uptake of glucose can also have a
limiting effect on glucose level variations (excursions), thus
treating both hyper- and hypoglycemia. In embodiments, methods of
treating glucose-related diseases can comprise applying systems of
the invention to a patient in need thereof. For example, LLEF or
LLMC systems can be applied to a patient's skin, or applied using a
catheter, or applied using a pharmaceutical composition. A
pharmaceutical composition disclosed herein can be administered to
an individual using a variety of routes. Routes of administration
suitable for use as disclosed herein include both local and
systemic administration. Local administration results in
significantly more delivery of a composition to a specific location
as compared to the entire body of the individual, whereas, systemic
administration results in delivery of a composition to essentially
the entire body of the individual.
[0162] Further, embodiments disclosed herein can direct cell
migration.
[0163] Further embodiments can increase cellular protein sulfhydryl
levels and cellular glucose uptake. Increased glucose uptake can
result in greater mitochondrial activity and thus increased glucose
utilization.
[0164] Muscle Regeneration
[0165] Embodiments of the disclosed LLMC and LLEF systems can be
used to regenerate muscle tissue. For example, embodiments can be
used to direct macrophage migration to damaged or wounded muscle
thus helping to regenerate the muscle.
[0166] Disclosed embodiments reduce or prevent muscle damage (for
example such as can occur during a workout), for example by
activating enzymes that aid in the muscle recovery process,
increasing glucose uptake, driving redox signaling, increasing
H.sub.2O.sub.2 production, increasing cellular protein sulfhydryl
levels, and increasing (IGF)-1 R phosphorylation.
[0167] Disclosed embodiments can improve muscle recovery, for
example by activating enzymes that aid in the muscle recovery
process, increasing glucose uptake, driving redox signaling,
increasing H.sub.2O.sub.2 production, increasing cellular protein
sulfhydryl levels, and increasing (IGF)-1 R phosphorylation.
Disclosed embodiments can improve muscle function, for example by
activating enzymes, increasing glucose uptake, driving redox
signaling, increasing H.sub.2O.sub.2 production, increasing
cellular protein sulfhydryl levels, and increasing (IGF)-1 R
phosphorylation. Disclosed embodiments can improve athletic
performance, for example by activating enzymes, increasing glucose
uptake, driving redox signaling, increasing H.sub.2O.sub.2
production, increasing cellular protein sulfhydryl levels, and
increasing (IGF)-1 R phosphorylation.
[0168] Embodiments disclosed herein include LLEC and LLEF systems
that can promote and/or accelerate the muscle recovery process and
optimize muscle performance. For example, muscles work when calcium
ions are released, which trigger muscle cells to contract. Proteins
called actin and myosin form filaments, which form cross-bridges
during contraction. The actin and myosin filaments pull past each
other when a flood of calcium ions signals contraction, and this
causes the muscle sheath to become shorter. This leads all the
sheaths (called "sarcomeres") to shorten, and the contraction is
synchronized across the entire muscle. The contracting muscles pull
on tendons, which in turn pull on the bones to which they are
attached. All muscle contractions are triggered by electrical
impulses which travel from the brain to the nerve endings in
contact with the actin and myosin filaments. Embodiments disclosed
herein can increase intracellular calcium levels.
[0169] Disclosed embodiments can accelerate muscle recover by, for
example, reducing or preventing lactic acidosis, for example by
increasing cellular excitation and/or mobilization, and increasing
energy production.
[0170] Methods disclosed herein can include applying a disclosed
embodiment to an area to be treated. Embodiments can include
selecting or identifying a patient in need of treatment. In
embodiments, methods disclosed herein can include application of a
device disclosed herein to an area to be treated.
[0171] In embodiments, disclosed methods include application to the
treatment area or the device of an antibacterial. In embodiments
the antibacterial can be, for example, alcohols, aldehydes,
halogen-releasing compounds, peroxides, anilides, biguanides,
bisphenols, halophenols, heavy metals, phenols and cresols,
quaternary ammonium compounds, and the like. In embodiments the
antibacterial agent can comprise, for example, ethanol,
isopropanol, glutaraldehyde, formaldehyde, chlorine compounds,
iodine compounds, hydrogen peroxide, ozone, peracetic acid,
formaldehyde, ethylene oxide, triclocarban, chlorhexidine,
alexidine, polymeric biguanides, triclosan, hexachlorophene, PCMX
(p-chloro-m-xylenol), silver compounds, mercury compounds, phenol,
cresol, cetrimide, benzalkonium chloride, cetylpyridinium chloride,
ceftolozane/tazobactam, ceftazidime/avibactam,
ceftaroline/avibactam, imipenem/MK-7655, plazomicin, eravacycline,
brilacidin, and the like.
[0172] In embodiments, compounds that modify resistance to common
antibacterials can be employed. For example, some
resistance-modifying agents may inhibit multidrug resistance
mechanisms, such as drug efflux from the cell, thus increasing the
susceptibility of bacteria to an antibacterial. In embodiments,
these compounds can include Phe-Arg-.beta.-naphthylamide, or
.beta.-lactamase inhibitors such as clavulanic acid and
sulbactam.
[0173] In embodiments, the system can also be used for preventative
treatment of tissue injuries. Preventative treatment can include
preventing the reoccurrence of previous muscle injuries. For
example, a garment can be shaped to fit a patient's shoulder to
prevent recurrence of a deltoid injury.
EXAMPLES
[0174] The following non-limiting examples are provided for
illustrative purposes only in order to facilitate a more complete
understanding of representative embodiments. These examples should
not be construed to limit any of the embodiments described in the
present specification.
Example 1
Cell Migration Assay
[0175] The in vitro scratch assay is an easy, low-cost and
well-developed method to measure cell migration in vitro. The basic
steps involve creating a "scratch" in a cell monolayer, capturing
images at the beginning and at regular intervals during cell
migration to close the scratch, and comparing the images to
quantify the migration rate of the cells. Compared to other
methods, the in vitro scratch assay is particularly suitable for
studies on the effects of cell-matrix and cell-cell interactions on
cell migration, mimic cell migration during wound healing in vivo
and are compatible with imaging of live cells during migration to
monitor intracellular events if desired. In addition to monitoring
migration of homogenous cell populations, this method has also been
adopted to measure migration of individual cells in the leading
edge of the scratch.
[0176] Human keratinocytes were plated under plated under placebo
or a LLEC system. Cells were also plated under silver-only or
zinc-only dressings. After 24 hours, the scratch assay was
performed. Cells plated under the LLEC system displayed increased
migration into the "scratched" area as compared to any of the zinc,
silver, or placebo dressings. After 9 hours, the cells plated under
the LLEC system had almost "closed" the scratch. This demonstrates
the importance of electrical activity to cell migration and
infiltration.
[0177] In addition to the scratch test, genetic expression was
tested. Increased insulin growth factor (IGF)-1 R phosphorylation
was demonstrated by the cells plated under the LLEC system as
compared to cells plated under insulin growth factor alone.
[0178] Integrin accumulation also affects cell migration. An
increase in integrin accumulation was achieved with the LLEC
system. Integrin is necessary for cell migration, and is found on
the leading edge of migrating cell.
[0179] Thus, the tested LLEC system enhanced cellular migration and
IGF-1 R/integrin involvement. This involvement demonstrates the
effect that the LLEC system had upon cell receptors involved with
the wound healing process.
Example 2
Wound Care Study
[0180] The medical histories of patients who received
"standard-of-care" wound treatment ("SOC"; n=20), or treatment with
a LLEC device as disclosed herein (n=18), were reviewed. The wound
care device used in the present study consisted of a discrete
matrix of silver and zinc dots. A sustained voltage of
approximately 0.8 V was generated between the dots. The electric
field generated at the device surface was measured to be 0.2-1.0 V,
10-50 .mu.A.
[0181] Wounds were assessed until closed or healed. The number of
days to wound closure and the rate of wound volume reduction were
compared. Patients treated with LLEC received one application of
the device each week, or more frequently in the presence of
excessive wound exudate, in conjunction with appropriate wound care
management. The LLEC was kept moist by saturating with normal
saline or conductive hydrogel. Adjunctive therapies (such as
negative pressure wound therapy [NPWT], etc.) were administered
with SOC or with the use of LLEC unless contraindicated. The SOC
group received the standard of care appropriate to the wound, for
example antimicrobial dressings, barrier creams, alginates, silver
dressings, absorptive foam dressings, hydrogel, enzymatic
debridement ointment, NPWT, etc. Etiology-specific care was
administered on a case-by-case basis. Dressings were applied at
weekly intervals or more. The SOC and LLEC groups did not differ
significantly in gender, age, wound types or the length, width, and
area of their wounds.
[0182] Wound dimensions were recorded at the beginning of the
treatment, as well as interim and final patient visits. Wound
dimensions, including length (L), width (W) and depth (D) were
measured, with depth measured at the deepest point. Wound closure
progression was also documented through digital photography.
Determining the area of the wound was performed using the length
and width measurements of the wound surface area.
[0183] Closure was defined as 100% epithelialization with visible
effacement of the wound. Wounds were assessed 1 week post-closure
to ensure continued progress toward healing during its maturation
and remodeling phase.
[0184] Wound types included in this study were diverse in etiology
and dimensions, thus the time to heal for wounds was distributed
over a wide range (9-124 days for SOC, and 3-44 days for the LLEC
group). Additionally, the patients often had multiple
co-morbidities, comprising diabetes, renal disease, and
hypertension. The average number of days to wound closure was 36.25
(SD=28.89) for the SOC group and 19.78 (SD=14.45) for the LLEC
group, p=0.036. On average, the wounds in the LLEC treatment group
attained closure 45.43% earlier than those in the SOC group.
[0185] Based on the volume calculated, some wounds improved
persistently while others first increased in size before improving.
The SOC and the LLEC groups were compared to each other in terms of
the number of instances when the dimensions of the patient wounds
increased (i.e., wound treatment outcome degraded). In the SOC
group, 10 wounds (50% for n=20) became larger during at least one
measurement interval, whereas 3 wounds (16.7% for n=18) became
larger in the LLEC group (p=0.018). Overall, wounds in both groups
responded positively. Response to treatment was observed to be
slower during the initial phase, but was observed to improve as
time progressed.
[0186] The LLEC wound treatment group demonstrated on average a
45.4% faster closure rate as compared to the SOC group. Wounds
receiving SOC were more likely to follow a "waxing-and-waning"
progression in wound closure compared to wounds in the LLEC
treatment group.
[0187] Compared to localized SOC treatments for wounds, the LLEC
(1) reduces wound closure time, (2) has a steeper wound closure
trajectory, and (3) has a more robust wound healing trend with
lower incidence of increased wound dimensions during the course of
healing.
Example 3
LLEC Influence on Human Keratinocyte Migration
[0188] An LLEC-generated electrical field was mapped, leading to
the observation that LLEC generates hydrogen peroxide, known to
drive redox signaling. LLEC-induced phosphorylation of
redox-sensitive IGF-1 R was directly implicated in cell migration.
The LLEC also increased keratinocyte mitochondrial membrane
potential.
[0189] The LLEC was made of polyester printed with dissimilar
elemental metals. It comprises alternating circular regions of
silver and zinc dots, along with a proprietary, biocompatible
binder added to lock the electrodes to the surface of a flexible
substrate in a pattern of discrete reservoirs. When the LLEC
contacts an aqueous solution, the silver positive electrode
(cathode) is reduced while the zinc negative electrode (anode) is
oxidized. The LLEC used herein consisted of metals placed in
proximity of about 1 mm to each other thus forming a redox couple
and generating an ideal potential on the order of 1 Volt. The
calculated values of the electric field from the LLEC were
consistent with the magnitudes that are typically applied (1-10
V/cm) in classical electrotaxis experiments, suggesting that cell
migration observed with the bioelectric dressing is likely due to
electrotaxis.
[0190] Measurement of the potential difference between adjacent
zinc and silver dots when the LLEC is in contact with de-ionized
water yielded a value of about 0.2 Volts. Though the potential
difference between zinc and silver dots can be measured,
non-intrusive measurement of the electric field arising from
contact between the LLEC and liquid medium was difficult.
Keratinocyte migration was accelerated by exposure to an Ag/Zn
LLEC. Replacing the Ag/Zn redox couple with Ag or Zn alone did not
reproduce the effect of keratinocyte acceleration.
[0191] Exposing keratinocytes to an LLEC for 24 h significantly
increased green fluorescence in the dichlorofluorescein (DCF) assay
indicating generation of reactive oxygen species under the effect
of the LLEC. To determine whether H.sub.2O.sub.2 is generated
specifically, keratinocytes were cultured with a LLEC or placebo
for 24 h and then loaded with PF6-AM (Peroxyfluor-6 acetoxymethyl
ester; an indicator of endogenous H.sub.2O.sub.2). Greater
intracellular fluorescence was observed in the LLEC keratinocytes
compared to the cells grown with placebo. Over-expression of
catalase (an enzyme that breaks down H.sub.2O.sub.2) attenuated the
increased migration triggered by the LLEC. Treating keratinocytes
with N-Acetyl Cysteine (which blocks oxidant-induced signaling)
also failed to reproduce the increased migration observed with
LLEC. Thus, H.sub.2O.sub.2 signaling mediated the increase of
keratinocyte migration under the effect of the electrical
stimulus.
[0192] External electrical stimulus can up-regulate the TCA
(tricarboxylic acid) cycle. The stimulated TCA cycle is then
expected to generate more NADH and FADH.sub.2 to enter into the
electron transport chain and elevate the mitochondrial membrane
potential (Am). Fluorescent dyes JC-1 and TMRM were used to measure
mitochondrial membrane potential. JC-1 is a lipophilic dye which
produces a red fluorescence with high Am and green fluorescence
when Am is low. TMRM produces a red fluorescence proportional to
Am. Treatment of keratinocytes with LLEC for 24 h demonstrated
significantly high red fluorescence with both JC-1 and TMRM,
indicating an increase in mitochondrial membrane potential and
energized mitochondria under the effect of the LLEC. As a potential
consequence of a stimulated TCA cycle, available pyruvate (the
primary substrate for the TCA cycle) is depleted resulting in an
enhanced rate of glycolysis. This can lead to an increase in
glucose uptake in order to push the glycolytic pathway forward. The
rate of glucose uptake in HaCaT cells treated with LLEC was
examined next. More than two fold enhancement of basal glucose
uptake was observed after treatment with LLEC for 24 h as compared
to placebo control.
[0193] Keratinocyte migration is known to involve phosphorylation
of a number of receptor tyrosine kinases (RTKs). To determine which
RTKs are activated as a result of LLEC, scratch assay was performed
on keratinocytes treated with LLEC or placebo for 24 h. Samples
were collected after 3 h and an antibody array that allows
simultaneous assessment of the phosphorylation status of 42 RTKs
was used to quantify RTK phosphorylation. It was determined that
LLEC significantly induces IGF-1 R phosphorylation. Sandwich ELISA
using an antibody against phospho-IGF-1 R and total IGF-1 R
verified this determination. As observed with the RTK array
screening, potent induction in phosphorylation of IGF-1 R was
observed 3 h post scratch under the influence of LLEC. IGF-1 R
inhibitor attenuated the increased keratinocyte migration observed
with LLEC treatment.
[0194] MBB (monobromobimane) alkylates thiol groups, displacing the
bromine and adding a fluoresce nt tag (lamda emission=478 nm). MCB
(monochlorobimane) reacts with only low molecular weight thiols
such as glutathione. Fluorescence emission from UV laser-excited
keratinocytes loaded with either MBB or MCB was determined for 30
min. Mean fluorescence collected from 10,000 cells showed a
significant shift of MBB fluorescence emission from cells. No
significant change in MCB fluorescence was observed, indicating a
change in total protein thiol but not glutathione. HaCaT cells were
treated with LLEC for 24 h followed by a scratch assay. Integrin
expression was observed by immuno-cytochemistry at different time
points. Higher integrin expression was observed 6 h post scratch at
the migrating edge.
[0195] Consistent with evidence that cell migration requires
H.sub.2O.sub.2 sensing, we determined that by blocking
H.sub.2O.sub.2 signaling by decomposition of H.sub.2O.sub.2 by
catalase or ROS scavenger, N-acetyl cysteine, the increase in
LLEC-driven cell migration is prevented. The observation that the
LLEC increases H.sub.2O.sub.2 production is significant because in
addition to cell migration, hydrogen peroxide generated in the
wound margin tissue is required to recruit neutrophils and other
leukocytes to the wound, regulates monocyte function, and VEGF
signaling pathway and tissue vascularization. Therefore, external
electrical stimulation can be used as an effective strategy to
deliver low levels of hydrogen peroxide over time to mimic the
environment of the healing wound and thus should help improve wound
outcomes. Another phenomenon observed during re-epithelialization
is increased expression of the integrin subunit alpha-v. There is
evidence that integrin, a major extracellular matrix receptor,
polarizes in response to applied ES and thus controls directional
cell migration. It may be noted that there are a number of integrin
subunits, however we chose integrin aV because of evidence of
association of alpha-v integrin with IGF-1 R, modulation of IGF-1
receptor signaling, and of driving keratinocyte locomotion.
Additionally, integrin alpha v has been reported to contain vicinal
thiols that provide site for redox activation of function of these
integrins and therefore the increase in protein thiols that we
observe under the effect of ES may be the driving force behind
increased integrin mediated cell migration. Other possible
integrins which may be playing a role in LLEC-induced IGF-1 R
mediated keratinocyte migration are a5 integrin and a6
integrin.
MATERIALS AND METHODS
[0196] Cell culture--Immortalized HaCaT human keratinocytes were
grown in Dulbecco's low-glucose modified Eagle's medium (Life
Technologies, Gaithersburg, Md., U.S.A.) supplemented with 10%
fetal bovine serum, 100 U/ml penicillin, and 100 .mu.g/ml
streptomycin. The cells were maintained in a standard culture
incubator with humidified air containing 5% CO2 at 37.degree.
C.
[0197] Scratch assay--A cell migration assay was performed using
culture inserts (IBIDI.RTM., Verona, Wis.) according to the
manufacturers instructions. Cell migration was measured using
time-lapse phase-contrast microscopy following withdrawal of the
insert. Images were analyzed using the AxioVision Rel 4.8
software.
[0198] N-Acetyl Cysteine Treatment--Cells were pretreated with 5 mM
of the thiol antioxidant N-acetylcysteine (Sigma) for 1 h before
start of the scratch assay.
[0199] IGF-1 R inhibition--When applicable, cells were preincubated
with 50 nM IGF-1 R inhibitor, picropodophyllin (Calbiochem, Mass.)
just prior to the Scratch Assay.
[0200] Cellular H.sub.2O.sub.2 Analysis--To determine intracellular
H.sub.2O.sub.2 levels, HaCaT cells were incubated with 5 pM PF6-AM
in PBS for 20 min at room temperature. After loading, cells were
washed twice to remove excess dye and visualized using a Zeiss
Axiovert 200M microscope.
[0201] Catalase gene delivery--HaCaT cells were transfected with
2.3.times.107 pfu AdCatalase or with the empty vector as control in
750 .mu.l of media. Subsequently, 750 .mu.l of additional media was
added 4 h later and the cells were incubated for 72 h.
[0202] RTK Phosphorylation Assay--Human Phospho-Receptor Tyrosine
Kinase phosphorylation was measured using Phospho-RTK Array kit (R
& D Systems).
[0203] ELISA--Phosphorylated and total IGF-1 R were measured using
a DuoSet IC ELISA kit from R&D Systems.
[0204] Determination of Mitochondrial Membrane
Potential--Mitochondrial membrane potential was measured in HaCaT
cells exposed to the LLEC or placebo using TMRM or JC-1 (MitoProbe
JC-1 Assay Kit for Flow Cytometry, Life Technologies), per
manufacturers instructions for flow cytometry.
[0205] Integrin alpha V Expression--Human HaCaT cells were grown
under the MCD or placebo and harvested 6 h after removing the
IBIDI.RTM. insert. Staining was done using antibody against
integrin aV (Abeam, Cambridge, Mass.).
Example 4
Generation of Superoxide
[0206] A LLEC system was tested to determine the effects on
superoxide levels which can activate signal pathways. LLEC system
increased cellular protein sulfhydryl levels. Further, the LLEC
system increased cellular glucose uptake in human keratinocytes.
Increased glucose uptake can result in greater mitochondrial
activity and thus increased glucose utilization, providing more
energy for cellular migration and proliferation. This can "prime"
the wound healing process before a surgical incision is made and
thus speed incision healing.
Example 5
Effect on Propionibacterium acnes
[0207] Bacterial Strains and Culture
[0208] The main bacterial strain used in this study is
Propionibacterium acnes and multiple antibiotics-resistant P. acnes
isolates are to be evaluated.
[0209] ATCC medium (7 Actinomyces broth) (BD) and/or ATCC medium
(593 chopped meat medium) is used for culturing P. acnes under an
anaerobic condition at 37.degree. C. All experiments are performed
under anaerobic conditions.
[0210] Culture
[0211] LNA (Leeming-Notman agar) medium is prepared and cultured at
34.degree. C. for 14 days.
[0212] Planktonic Cells
[0213] P. acnes is a relatively slow-growing, typically
aero-tolerant anaerobic, Gram-positive bacterium (rod). P. acnes is
cultured under anaerobic condition to determine for efficacy of an
embodiment disclosed herein (LLEC system). Overnight bacterial
cultures are diluted with fresh culture medium supplemented with
0.1% sodium thioglycolate in PBS to10.sup.5 colony forming units
(CFUs). Next, the bacterial suspensions (0.5 mL of about 105) are
applied directly on LLEC system (2''.times.2'') and control fabrics
in Petri-dishes under anaerobic conditions. After 0 h and 24 h post
treatments at 37.degree. C., portions of the sample fabrics are
placed into anaerobic diluents and vigorously shaken by vortexing
for 2 min. The suspensions are diluted serially and plated onto
anaerobic plates under an anaerobic condition. After 24 h
incubation, the surviving colonies are counted. The LLEC limits
bacterial proliferation.
Example 6
Metallic Gel Solution and Single-Metal Substrate
[0214] This study demonstrated an alternative method of producing a
Redox reaction voltage between two metals (such as zinc and
silver), without having both metals embedded in the same substrate.
By removing one of the metals from the substrate and mixing it with
a conductive gel, the voltage potential was comparable to the
voltage potential of both metals embedded in the substrate
(PROCELLERA.RTM.).
TABLE-US-00001 Observed Voltage Potential Zinc only Substrate
Silver only Substrate Silver Gel .ltoreq..75 V n/a Solution Zinc
Gel n/a .ltoreq..85 V Solution Pure Gel .ltoreq..45 V .ltoreq..25 V
Solution *Gel used was sterile AquaSonic 100 by Parker Labs
Example 7
Pre-Treatment and Post-Treatment of Surgical Procedures
[0215] Prior to surgery the patient can apply or wear a LLEC system
hydrogel over the surgical site, such as the upper arm or bicep
area. Surgical procedures can comprise procedures used to treat
tenotomy, subpec biceps tenodesis, or rotor cuff repair. The
hydrogel consists of an integrated layer of a standard LLEC system.
Prior to applying or wearing hydrogel device an activating agent
may be applied. The viscosity of the hydrogel provides an intimate
contact between the electrodes within the hydrogel device and the
skin with minimal movement.
[0216] The hydrogel with integrated LLEC system can be applied or
worn for 24 hours prior to surgery to initiate incision-healing
process by; 1) reducing or eliminating microorganism presence
around the incision site; 2) increasing integrin accumulation; 3)
increasing cellular protein sulfhydryl levels; 4) increasing
H.sub.2O.sub.2 production; and 5) up-regulating the TCA
(tricarboxylic acid) cycle.
[0217] The same LLEC hydrogel device and method can also be applied
to a patient's surgical site post-surgery for accelerated healing
or treatment.
Example 8
Availability of Cellular Energy and Lactate Threshold
[0218] The lactate threshold, also known as lactate inflection
point or anaerobic threshold, is the exercise intensity at which
lactate (more specifically, lactic acid) starts to accumulate in
the blood stream. The reason for the acidification of the blood at
high exercise intensities is two-fold: the high rates of ATP
hydrolysis in the muscle release hydrogen ions, as they are
co-transported out of the muscle into the blood via the
monocarboxylate transporter, and also bicarbonate stores in the
blood begin to be used up. This happens when lactate is produced
faster than it can be removed (metabolized) in the muscle. When
exercising at or below the lactate threshold, any lactate produced
by the muscles is removed by the body without it building up (e.g.,
aerobic respiration). When exercising at or above the lactate
threshold (e.g. anaerobic respiration), excess lactate can build up
in tissue causing a lower pH and soreness, called acidosis. This
excess lactate build-up decreases athletic ability during exercise
as well tissue recovery after exercise.
[0219] Prior to exercise or activity the patient applies or wears a
LLEC hydrogel device to his body, such as the upper body using a
shirt, the lower body using pants, applying a hydrogel ointment to
ankle, or a combination of the like. The hydrogel consists of
integrated microparticles of a standard LLEC system. The LLEC
system can be configured to penetrate into superficial muscle
tissue under the hydrogel. The LLEC system increased cellular
glucose uptake. Increased glucose uptake can result in greater
mitochondrial activity and thus increased glucose utilization,
providing more energy for cellular activity to remove lactic acid
from muscle tissue. It has been shown that an increased cellular
glucose utilization can also sustain anaerobic respiration for a
longer period of time during exercise, thus increasing a person's
lactate threshold. An increased lactate threshold prevents lactate
from building-up in muscle tissue and strengthens sustainable
athletic performance for longer periods of time.
Example 9
Three Dimensional Energy Source for Clothing, Prosthetics, or
Medical Devices
[0220] The three-dimensional energy source can be used to supply
power to low-energy devices worn as clothing, prosthetic devices,
and medical devices. For example a clothing material can be
constructed of a bioelectric hydrogel to comprise sensors to detect
temperature of a patient's skin. The LLEC system of the hydrogel
can be configured to supply power to the sensor detecting the skin
temperature. Additionally, the energy source can be supplied by the
clothing to a near by object requiring power such as a pacemaker
under the chest tissue. In particular, the LLEC hydrogel system can
be worn as a shirt and transmit power to a pacemaker directly under
the skin.
[0221] In another example, a bioelectric hydrogel can be used to
manufacture an electrical prosthetic. In particular, a prosthetic
can be manufactured to comprise a hydrogel with a three-dimensional
energy source to power the electronics or recharge the battery of
the prosthetic.
[0222] In another example, a bioelectric hydrogel can be
manufactured into a pacemaker. In particular, a pacemaker can be
manufactured to comprise a hydrogel to provide power to the
pacemaker for a specified period of time.
Example 10
Three Dimensional Energy Source for Cell Culture
[0223] Neuro cells and nerve ganglions are very difficult to grow
in vitro. Current cellular medium cannot provide the appropriate
energy or nutrients to sustain such cells in vitro. The energy
environment present in a three dimensional energy source, such as
the disclosed hydrogel, can make for a more stable environment for
cellular growth. The addition of nutrients to the hydrogel cellular
medium can make it possible to grow and maintain the neural cells
and nerve ganglia in vitro.
[0224] The hydrogel can also be formed or shaped into a Petri dish.
In particular, hydrogel can be configured to be a high viscosity
and molded into a Petri dish for cellular culture. Specifically,
the hydrogel Petri dish can provide a three dimensional energy
source to the cultured medium being held by the Petri dish and make
it possible to grow and maintain the neural cells and nerve ganglia
in vitro.
Example 11
Treatment of Open Fracture
[0225] A 15-year old male suffers a grade-III open tibia-fibula
fracture, leaving exposed bone and muscle. The wound is dressed
with LLEC systems as described herein comprising a bioelectric
device containing an array of biocompatible microcells and a
hydrogel containing an array of biocompatible microcells. The wound
heals without the need of muscle or skin grafts. The wound is also
kept free from microbial contamination as a result of the
broad-spectrum antimicrobial effect of the systems as disclosed
herein.
Example 12
Treatment of an Insect Bite
[0226] A 25-year old male suffers numerous mosquito bites along his
legs. A LLEC system including a pliable dressing material as
described herein comprising a bioelectric device containing an
array of biocompatible microcells and a hydrogel containing an
array of biocompatible microcells is wrapped around his legs. The
LLEC system reduces the swelling and eliminates the itching caused
by the bites within 3 hours.
Example 13
Treatment of a Venomous Snake Bite
[0227] A 25-year old male suffers a venomous snake bite to his leg.
Bleeding is stopped then the wound is dressed with a LLMC system
comprising a bioelectric dressing containing an array of
biocompatible microcells and a hydrogel containing an array of
biocompatible microcells. The venom injected during the bite is
neutralized. Over the next 2 weeks the wound heals. The wound is
also kept free from microbial contamination as a result of the
broad-spectrum antimicrobial effect of the wound management systems
disclosed herein.
Example 14
Treatment of Diabetes
[0228] A 48-year old woman suffers from type 2 diabetes. To limit
glucose excursions and lower serum glucose levels, LLEF systems
comprising an array of biocompatible microcells and a hydrogel
containing an array of biocompatible microcells are applied around
the patient's abdomen and extremities. This increases cellular
glucose uptake and reduces serum glucose levels, as well as
moderating glucose excursions.
[0229] In closing, it is to be understood that although aspects of
the present specification are highlighted by referring to specific
embodiments, one skilled in the art will readily appreciate that
these disclosed embodiments are only illustrative of the principles
of the subject matter disclosed herein. Therefore, it should be
understood that the disclosed subject matter is in no way limited
to a particular methodology, protocol, and/or reagent, etc.,
described herein. As such, various modifications or changes to or
alternative configurations of the disclosed subject matter can be
made in accordance with the teachings herein without departing from
the spirit of the present specification. Lastly, the terminology
used herein is for the purpose of describing particular embodiments
only, and is not intended to limit the scope of the present
disclosure, which is defined solely by the claims. Accordingly,
embodiments of the present disclosure are not limited to those
precisely as shown and described.
[0230] In closing, it is to be understood that although aspects of
the present specification are highlighted by referring to specific
embodiments, one skilled in the art will readily appreciate that
these disclosed embodiments are only illustrative of the principles
of the subject matter disclosed herein. Therefore, it should be
understood that the disclosed subject matter is in no way limited
to a particular methodology, protocol, and/or reagent, etc.,
described herein. As such, various modifications or changes to or
alternative configurations of the disclosed subject matter can be
made in accordance with the teachings herein without departing from
the spirit of the present specification. Lastly, the terminology
used herein is for the purpose of describing particular embodiments
only, and is not intended to limit the scope of the present
disclosure, which is defined solely by the claims. Accordingly,
embodiments of the present disclosure are not limited to those
precisely as shown and described.
[0231] Certain embodiments are described herein, comprising the
best mode known to the inventor for carrying out the methods and
devices described herein. Of course, variations on these described
embodiments will become apparent to those of ordinary skill in the
art upon reading the foregoing description. Accordingly, this
disclosure comprises all modifications and equivalents of the
subject matter recited in the claims appended hereto as permitted
by applicable law. Moreover, any combination of the above-described
embodiments in all possible variations thereof is encompassed by
the disclosure unless otherwise indicated herein or otherwise
clearly contradicted by context.
[0232] Groupings of alternative embodiments, elements, or steps of
the present disclosure are not to be construed as limitations. Each
group member may be referred to and claimed individually or in any
combination with other group members disclosed herein. It is
anticipated that one or more members of a group may be comprised
in, or deleted from, a group for reasons of convenience and/or
patentability. When any such inclusion or deletion occurs, the
specification is deemed to contain the group as modified thus
fulfilling the written description of all Markush groups used in
the appended claims.
[0233] Unless otherwise indicated, all numbers expressing a
characteristic, item, quantity, parameter, property, term, and so
forth used in the present specification and claims are to be
understood as being modified in all instances by the term "about."
As used herein, the term "about" means that the characteristic,
item, quantity, parameter, property, or term so qualified
encompasses a range of plus or minus ten percent above and below
the value of the stated characteristic, item, quantity, parameter,
property, or term. Accordingly, unless indicated to the contrary,
the numerical parameters set forth in the specification and
attached claims are approximations that may vary. At the very
least, and not as an attempt to limit the application of the
doctrine of equivalents to the scope of the claims, each numerical
indication should at least be construed in light of the number of
reported significant digits and by applying ordinary rounding
techniques. Notwithstanding that the numerical ranges and values
setting forth the broad scope of the disclosure are approximations,
the numerical ranges and values set forth in the specific examples
are reported as precisely as possible. Any numerical range or
value, however, inherently contains certain errors necessarily
resulting from the standard deviation found in their respective
testing measurements. Recitation of numerical ranges of values
herein is merely intended to serve as a shorthand method of
referring individually to each separate numerical value falling
within the range. Unless otherwise indicated herein, each
individual value of a numerical range is incorporated into the
present specification as if it were individually recited
herein.
[0234] The terms "a," "an," "the" and similar referents used in the
context of describing the disclosure (especially in the context of
the following claims) are to be construed to cover both the
singular and the plural, unless otherwise indicated herein or
clearly contradicted by context. All methods described herein can
be performed in any suitable order unless otherwise indicated
herein or otherwise clearly contradicted by context. The use of any
and all examples, or exemplary language (e.g., "such as") provided
herein is intended merely to better illuminate the disclosure and
does not pose a limitation on the scope otherwise claimed. No
language in the present specification should be construed as
indicating any non-claimed element essential to the practice of
embodiments disclosed herein.
[0235] Specific embodiments disclosed herein may be further limited
in the claims using consisting of or consisting essentially of
language. When used in the claims, whether as filed or added per
amendment, the transition term "consisting of" excludes any
element, step, or ingredient not specified in the claims. The
transition term "consisting essentially of" limits the scope of a
claim to the specified materials or steps and those that do not
materially affect the basic and novel characteristic(s).
Embodiments of the present disclosure so claimed are inherently or
expressly described and enabled herein.
* * * * *