U.S. patent application number 17/630077 was filed with the patent office on 2022-08-25 for compositions and methods for treating bone fractures.
The applicant listed for this patent is ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA, Hamid SAADATMANESH, Mehrnoosh ZARKOOB. Invention is credited to Hamid Saadatmanesh, Mehrnoosh Zarkoob.
Application Number | 20220265428 17/630077 |
Document ID | / |
Family ID | 1000006364149 |
Filed Date | 2022-08-25 |
United States Patent
Application |
20220265428 |
Kind Code |
A1 |
Saadatmanesh; Hamid ; et
al. |
August 25, 2022 |
COMPOSITIONS AND METHODS FOR TREATING BONE FRACTURES
Abstract
Provided herein are compositions and methods for treating bone
fractures. In particular, provided herein are systems comprising
carbon fiber sleeves and biocompatible polymers and the use of such
systems in treating or preventing bone fractures.
Inventors: |
Saadatmanesh; Hamid;
(Tucson, AZ) ; Zarkoob; Mehrnoosh; (Tucson,
AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SAADATMANESH; Hamid
ZARKOOB; Mehrnoosh
ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF
ARIZONA |
Tucson
Tucson
Tucson |
AZ
AZ
AZ |
US
US
US |
|
|
Family ID: |
1000006364149 |
Appl. No.: |
17/630077 |
Filed: |
July 24, 2020 |
PCT Filed: |
July 24, 2020 |
PCT NO: |
PCT/US2020/043373 |
371 Date: |
January 25, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62878484 |
Jul 25, 2019 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2310/00161
20130101; A61F 2/2846 20130101; A61L 27/54 20130101; A61F 2002/2839
20130101; A61L 2300/404 20130101; A61L 27/08 20130101; A61L 27/56
20130101 |
International
Class: |
A61F 2/28 20060101
A61F002/28; A61L 27/08 20060101 A61L027/08; A61L 27/56 20060101
A61L027/56; A61L 27/54 20060101 A61L027/54 |
Claims
1.-52. (canceled)
53. A method of treating, stabilizing, or preventing a bone
fracture or strengthening a bone, comprising: a. making at least
one hole through said bone; and b. inserting a fiber tube in said
first hole; and c. filling said fiber tube with a biocompatible
polymer.
54. The method of claim 53, wherein said at least one hole
comprises first and second holes, and wherein a first of said holes
is placed on the proximal side of said bone fracture and a second
of said holes is on the distal side of said bone fracture, and
wherein said fiber tube is placed between said first and second
holes.
55. The method of claim 53, wherein said fiber tube is a carbon
fiber tube, an ultrathin layer of carbon fabric, or a double
layered bag comprising outer porous carbon fiber layer and inner
non-porous carbon fiber layer.
56. The method of claim 53, wherein said fiber tube comprises one
or more surface modifications selected from the group consisting of
electrochemical, chemical, thermal, discharge plasma, and radiation
treatment.
57. The method of claim 56, wherein said surface modifications
comprise antimicrobial agents selected from the group consisting of
cationic groups such as quaternary ammonium compounds, metal-based
antimicrobials such as silver or bismuth, polymer-based
antimicrobials such as polyhexamethylene biguanide, and oxidizing
agents such as hydrogen peroxide.
58. The method of claim 53, wherein said carbon fiber tube is
pre-impregnated with a resin system at a temperature below the
physiological temperature and resin system polymerizes at
physiological temperature after insertion of said carbon fiber tube
in said bone.
59. The method of claim 53, wherein said biocompatible polymer is
selected from the group consisting of calcium phosphate,
poly(lactic-co-glycolic) acid, polyanhydrides, polyvinylchloride
(PVC), polyethylene (PE), polypropylene (PP), polymethylmetacrylate
(PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE),
polyurethane (PU), polyamide (nylon), polyethylenterephthalate
(PET), polyethersulfone (PES), polycarbonates (PC), polyetherimide
(PEI), Polycaprolactone (PCL), and mineralized bone particles
(MBP).
60. The method of claim 53, wherein said biocompatible polymer
comprises a depolymerization agent selected from the group
consisting of gold nanoparticles, photolabile crosslinkers,
degradable crosslinkers such as 1,4-diacetylbenzene
1,4-bis(O-methacryloyl)dioxime and 1,3,5-triacetylbenzene
1,3,5-tris(O-methacryloyl)trioxime.
61. The method of claim 53, wherein said biocompatible polymer is
pre-compressed before filling, is an expansive polymer, and
comprises a carbon fiber reinforcing component.
62. The method of claim 53, wherein said inserting said fiber tube
comprises the steps of creating holes that are drilled or using
laparoscopy, inserting said carbon fiber tube in said first of said
holes and drawing said carbon fiber tube via a lead wire that exits
said second of said holes.
63. The method of claim 53, wherein said fiber tube or said
biocompatible polymer further comprises one or more active agents
selected from the group consisting of a drug, antimicrobial agent,
antibiotic, bone healing promoting agent, chemotherapeutic agent,
or bone precursor such as osteoblast or osteoclast.
64. A method of treating, stabilizing, or preventing a bone
fracture or strengthening a bone, comprising: a. making at least
one hole through said bone; and b. inserting a fiber tube in said
first hole; and c. filling said fiber tube with a biocompatible
polymer wherein said fiber tube is either permanent or said fiber
tube is removal.
65. The method of claim 64, wherein said fiber is removed by
exposing said gold nanoparticles to radiofrequency or said
photolabile crosslinkers to UV light.
66. The method of claim 64, wherein at least one physical property
of said biocompatible polymer is altered by an external stimulus
that is either electrical or thermal energy.
67. The method of claim 64, wherein said fiber tube is configured
to resist compressive, torsional, and shear forces when placed in a
bone, conforms to the shape of a bone cavity in said bone, or is
configured to retain tube shape after placement in said bone.
68. The method of claim 64, wherein said fracture is selected from
the group consisting of stable fractures, open, compound fractures,
transverse fractures, oblique fractures, and comminuted
fractures.
69. The method of claim 64, wherein said fracture is in a bone
selected from the group consisting of the clavicle, sternum,
phalanges, metacarpals, radius, ulna, hip, femur, tibia, and
fibula.
70. The method of claim 64, wherein said treating, stabilizing, or
preventing a bone fracture or strengthening a bone is for human or
non-human animal that has a bone injury, has increased risk of a
bone fracture, has overuse condition, has cancer or
osteoporosis.
71. A kit or system, comprising: a. a fiber tube; and b. a
biocompatible polymer; and c. one or more of a guide wire; an
implant retrieval system; and a fiber reinforcing component.
72. The kit or system of claim 71 for use in treating, stabilizing,
or preventing a bone fracture or strengthening a bone.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and the benefit of U.S.
Provisional Application No. 62/878,484, filed Jul. 25, 2019, which
is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] Provided herein are compositions and methods for treating
and stabilizing bone fractures. In particular, provided herein are
systems comprising fiber sleeves and biocompatible polymers and the
use of such systems in treating bone fractures.
BACKGROUND OF THE INVENTION
[0003] A bone fracture is a medical condition where the continuity
of the bone is broken. A significant percentage of bone fractures
occur because of high force impact or stress. However, a fracture
may also be the result of medical conditions that weaken the bones,
for example osteoporosis, some cancers, or osteogenesis
imperfecta.
[0004] Bone healing is a process which in most cases occurs
naturally. Fracture treatment is usually aimed at making sure there
is the best possible function of the injured part after healing.
Treatment also focuses on providing the injured bone with the best
circumstances for optimum healing (e.g., immobilization with
internal or external stabilization). For the natural healing
process to begin, the ends of the broken bone need to be lined up;
this is known as reducing the fracture. Fracture reduction may be
done by manipulation, closed reduction (pulling the bone
fragments), or surgery.
[0005] As soon as the bones are aligned they must stay aligned
while they heal. This may include: plaster casts or plastic
functional braces that these hold the bone in position until it has
healed; metal plates and screws that may use minimally invasive
techniques; intra-medullary nails, which are internal metal rods or
flexible wire that are placed down the center of long bones; and
external fixators made of metal or carbon fiber that have steel
pins that go into the bone directly through the skin.
[0006] Usually, the fractured bone area is immobilized for 2-8
weeks. The duration depends on which bone is affected and whether
there are any complications, such as a blood supply problem or an
infection.
[0007] Improved methods for aligning and immobilizing and
stabilizing fractures and preventing factures in bones at risk of
fracture are needed.
SUMMARY OF THE INVENTION
[0008] Almost all major bone fractures require some form of
incision to allow bone alignment and attachment of stabilizing
rods, brackets, etc. Such incisions typically create significant
trauma and require extensive rehabilitation time.
[0009] U.S. Pat. No. 6,425,923 describes an orthopedic implant that
includes a flexible bag having at least a portion thereof which is
expandable under pressure; and a polymer within the bag. The
orthopedic implant is implanted within a bone by forming a cavity
in the bone; inserting a flexible bag into the cavity, the flexible
bag having at least a portion thereof which is expandable under
pressure; pressure filling the bag with a polymer, whereby the
expandable portion of the bag expands to substantially entirely
fill the cavity in the bone; and hardening the polymer. In
addition, U.S. Pat. App. No. 20100076503 describes a method of long
bone strengthening and a composite implant for such strengthening
(e.g., a plurality of rigid tensile rods, in matrix of cement and
surrounded by a partially porous bag). However, these, and other
existing solutions fail to meet the need for a bone repair,
strengthening system, and an infection prevention system that is
permanent (e.g., non-absorbable), while providing the option for
removal and further fail to provide a customizable solution for
each patient's need.
[0010] Provided herein is an improved method that eliminates the
need for any incision or internal containment bag and utilizes no
dissolvable or absorbable material and resists infection. The
method includes insertion of an ultra-thin, braided, woven, or
prepreg carbon fiber tube inside the bone cavity followed by the
injection of a biocompatible polymer inside the carbon fiber tube.
In this manner, a very strong dowel (e.g., ten times stronger than
steel) is created inside the bone cavity bridging the sides of the
fracture. The systems and methods described herein eliminate the
need for open cuts and result in significantly less trauma and
recovery time. In addition, the lack of metal eliminates potential
interference issues with imaging techniques such as MRI. The
systems and methods described herein provide a non-absorbable
solution for repair and strengthening of bones that can be left in
place permanently or removed if desired.
[0011] For example, in some embodiments, provided herein is a
method of treating or stabilizing (e.g., by strengthening a bone) a
bone fracture or strengthening a bone in a subject, comprising: a)
making at least one (e.g., 1, 2, 3, 4, or more) holes (e.g., on the
mm scale in diameter) through a bone, wherein optionally a first of
hole is placed on the proximal side of the bone fracture and an
optional second hole is on the distal side of the bone fracture;
and b) inserting a tube (e.g., carbon fiber tube) into a first hole
(e.g., optionally between the first and second holes); and
optionally c) filling the tube with a biocompatible polymer. In
some embodiments, the holes are drilled (e.g., using laparoscopy).
In some embodiments, the tube is a double layer carbon fiber tube.
In some embodiments, inserting the carbon fiber tube comprises the
steps of inserting the carbon fiber tube in the first hole and
drawing the carbon fiber tube via a lead wire that exits the second
hole. In some embodiments, the subject has a fracture. In some
embodiments, the subject is at increased risk of a fracture (e.g.,
due to overuse, injury, or disease (e.g., osteoporosis). In some
embodiments, the fiber tube is permanently placed in the bone. In
some embodiments, the fiber tube is removable (e.g., by activating
a depolymerization agent). In some embodiments, the fiber tube is
configured to resist compressive, torsional, and shear forces when
placed in a bone. In some embodiments, at least a portion of the
fiber tube conforms to the shape of a bone cavity in the bone or
retains a tube shape after placement in the bone.
[0012] The present disclosure is not limited to a particular
material or configuration of carbon or other fiber tube. In some
embodiments, the carbon fiber tube is ultrathin layer of carbon
fabric. In some embodiments, the carbon fiber tube is a multi
(e.g., double) layer bag comprising outer and inner carbon fiber
layers. In some embodiments, the outer carbon fiber layer is porous
and the inner carbon fiber layer is non-porous. In some
embodiments, the fiber tube comprises one or more surface
modifications (e.g., electrochemical, chemical, thermal, discharge
plasma, or radiation treatment). In some embodiments, the surface
modifications comprise or are antimicrobial agents (e.g., cationic
groups such as quaternary ammonium compounds, metal-based
antimicrobials such as silver or bismuth, polymer-based
antimicrobials such as polyhexamethylene biguanide and or oxidizing
agents such as hydrogen peroxide. In some embodiments, the carbon
fiber tube is pre-impregnated with a resin system that polymerizes
at a service temperature (e.g., a temperature lower than body
temperature). In some embodiments, the impregnated sleeve is kept
at lower than body temperature and when it is inserted in the body
it will start to polymerize at the body temperature, which is
higher than the storage temperature. In some embodiments, the resin
polymerizes after insertion of the carbon fiber sleeve in the
bone.
[0013] The present disclosure is not limited to a particular
biocompatible polymer. In some embodiments, the biocompatible
polymer is calcium phosphate, poly(lactic-co-glycolic) acid,
polyanhydrides, polyvinylchloride (PVC), polyethylene (PE),
polypropylene (PP), polymethylmetacrylate (PMMA), polystyrene (PS),
polytetrafluoroethylene (PTFE), polyurethane (PU), polyamide
(nylon), polyethylenterephthalate (PET), polyethersulfone (PES),
polycarbonates (PC), and polyetherimide (PEI), Polycaprolactone
(PCL), or mineralized bone particles (MBP). In some embodiments,
the biocompatible polymer comprises a depolymerization agent (e.g.,
gold nanoparticles or a degradable crosslinker (e.g.,
1,4-diacetylbenzene 1,4-bis(O-methacryloyl)dioxime or
1,3,5-triacetylbenzene 1,3,5-tris(O-methacryloyl)trioxime)). In
some embodiments, the polymer is pre-compressed before filling. In
some embodiments, the polymer is an expansive polymer (e.g.,
functionalized with crosslinkers for in situ polymerization). In
some embodiments, the biocompatible polymer is injected into the
fiber tube. In some embodiments, the biocompatible polymer
comprises a carbon fiber reinforcing component (e.g., including but
not limited to, carbon fiber spring or flexible internal scaffold).
In some embodiments, at least one physical property of the
biocompatible polymer is altered based on external stimulus (e.g.,
electrical or physical stimulus).
[0014] In some embodiments, the fiber tube and/or biocompatible
polymer further comprise an active agent. In some embodiments, the
active agent is an antimicrobial agent, a drug (e.g., antibiotic,
chemotherapeutic agent, or an agent that promotes bone healing
(e.g., growth factor) or bone precursor (e.g., osteoblast or
osteoclast).
[0015] Further embodiments provide a kit or system, comprising: a
fiber tube; and a biocompatible polymer and optionally an implant
retrieval system. In some embodiments, the kit or system further
comprises one of more of a guide wire and/or a carbon fiber
reinforcing component.
[0016] Additional embodiments provide a kit or system as described
herein for use in treating a bone fracture or strengthen a bone
(e.g., in a subject at risk of a fracture (e.g., a subject with
overuse, a bone injury, or disease (e.g., osteoporosis or
cancer)).
[0017] Additional embodiments provide the use of a kit or system
described herein for to treat a bone fracture or strengthen a bone
(e.g., in a subject at risk of a fracture (e.g., a subject with
overuse, a bone injury, or disease (e.g., osteoporosis or
cancer)).
[0018] The present disclosure is not limited to the treatment of a
particular type of fracture. Examples include, but are not limited
to, stable fractures, open, compound fractures, transverse
fractures, oblique fractures, and comminuted fractures of the
clavicle, sternum, phalanges, metacarpals, radius, ulna, hip,
femur, tibia, or fibula. In some embodiments, the subject has
osteoporosis.
[0019] The present disclosure is not limited to a particular
subject. In some embodiments, the subject is a human or non-human
animal (e.g., horse or companion animal).
[0020] Additional embodiments are described herein.
DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 shows a shear key that mechanically interlocks dowel
to bone.
[0022] FIG. 2 shows exemplary precompression of infill
material.
[0023] FIG. 3 shows internal carbon reinforcement in a carbon
sleeve.
[0024] FIG. 4 shows exemplary double layered carbon sleeves.
DEFINITIONS
[0025] To facilitate an understanding of the present invention, a
number of terms and phrases are defined below:
[0026] As used herein, the term "subject" refers to any animal
(e.g., a mammal), including, but not limited to, humans, non-human
primates, rodents, and the like, which is to be the recipient of a
particular treatment. Typically, the terms "subject" and "patient"
are used interchangeably herein in reference to a human or
non-subject.
[0027] As used herein, the term "non-human animals" refers to all
non-human animals including, but not limited to, vertebrates such
as rodents, non-human primates, ovines, bovines, ruminants,
lagomorphs, porcines, caprines, equines, canines, felines, ayes,
etc.
[0028] "Polymer" is any natural or synthetic molecule which can
form long molecular chains, such as polyolefin, polyamides,
polyesters, polyurethanes, polypeptides, polysaccharides, and
combinations thereof.
[0029] A "biocompatible polymer" is a polymer that does not produce
toxins or harmful products and preferably does not stimulate an
immune response in biological systems. Biocompatible polymers may
be natural or synthetic.
DETAILED DESCRIPTION OF THE INVENTION
[0030] Provided herein are improved systems and methods for bone
healing. The systems and methods described herein are minimally
invasive and provide strong, flexible supports for healing bone
breaks and support bones weakened by osteoporosis.
[0031] For example, in some embodiments, the present invention
provides a method for treating fractures and/or strengthening
bones. The basic procedure is as follows: first, at least one
(e.g., 1, 2, 3, 4, or more) small holes (e.g., mm scale each) are
drilled (e.g., laparoscopically) into and through a bone on
different sides of the fracture line (e.g., horizontally or
vertically, depending on the fracture). Next, a fiber (e.g., carbon
fiber) tube, sleeve, or bag is inserted into a hole. In some
embodiments, the fiber tube is drawn out through a lead wire or
other guide component through a second hole. In some embodiments, a
biocompatible resin is then injected into the tube, expanding it to
fully fill the bone cavity and creating an internal dowel bridging
the two sides of the fracture line, as shown in FIG. 1. the sleeve
bonds to the bone and act as a permanent solution rather than a
dissolvable and absorbable material. However, in some embodiments,
the components of the system are removable if desired.
[0032] The systems and methods described herein eliminate the need
for an open cut and result in significantly less trauma and
recovery time than existing methods, which require an open
incision. This technique is particularly effective in areas of the
body where bracing cannot be provided such as, for example,
fractures of the collar bone.
[0033] In some embodiments, after the access holes are filled, they
act as shear keys developing a mechanical interlock between the
internal hardened carbon sleeve and the bone, giving significant
structural integrity to the bone/sleeve combination, as shown in
FIG. 1.
[0034] The present disclosure is not limited to a particular type
of carbon fiber tube or carbon fiber material. Carbon fibers (CF,
graphite fiber) are fibers about 5-10 micrometres in diameter that
are composed mostly of carbon atoms. Carbon fibers have several
advantages including, but not limited to, high stiffness, high
tensile strength, low weight, high chemical resistance, high
temperature tolerance and low thermal expansion. These properties
have made carbon fiber very popular in aerospace, civil
engineering, military, and motorsports, along with other
competition sports.
[0035] To produce a carbon fiber, the carbon atoms are bonded
together in crystals that are more or less aligned parallel to the
long axis of the fiber as the crystal alignment gives the fiber
high strength-to-volume ratio (making it strong for its size).
Several thousand carbon fibers are bundled together to form a tow,
which may be used by itself or woven into a fabric.
[0036] Carbon fibers are usually combined with other materials to
form a composite. When impregnated with a resin, they form
carbon-fiber-reinforced polymer (often referred to as carbon fiber)
which has a very high strength-to-weight ratio and is extremely
rigid. Carbon fibers are also composited with other materials, such
as graphite, to form reinforced carbon-carbon composites, which
have a very high heat tolerance.
[0037] Carbon fiber is frequently supplied in the form of a
continuous tow wound onto a reel. The tow is a bundle of thousands
of continuous individual carbon filaments held together and
protected by an organic coating, or size, such as polyethylene
oxide (PEO) or polyvinyl alcohol (PVA). The tow can be conveniently
unwound from the reel for use. Each carbon filament in the tow is a
continuous cylinder with a diameter of 5-10 micrometers and is
almost exclusively carbon.
[0038] The atomic structure of carbon fiber is similar to that of
graphite, comprising sheets of carbon atoms arranged in a regular
hexagonal pattern (graphene sheets), the difference being in the
way these sheets interlock. Graphite is a crystalline material in
which the sheets are stacked parallel to one another in regular
fashion. The intermolecular forces between the sheets are
relatively weak Van der Waals forces, giving graphite its soft and
brittle characteristics. Precursors for carbon fibers are
polyacrylonitrile (PAN), rayon and pitch. Carbon fiber filament
yarns are used in several processing techniques: the direct uses
are for prepregging, filament winding, pultrusion, weaving,
braiding, etc. Carbon fiber yarn is rated by the linear density
(weight per unit length; i.e., 1 g/1000 m=1 tex) or by number of
filaments per yarn count, in thousands. For example, 200 tex for
3,000 filaments of carbon fiber is three times as strong as 1,000
carbon filament yarn but is also three times as heavy. This thread
can then be used to weave a carbon fiber filament fabric or cloth.
The appearance of this fabric generally depends on the linear
density of the yarn and the weave chosen. Some commonly used types
of weave are twill, satin and plain. Carbon filament yarns can also
be knitted or braided.
[0039] Each carbon filament is produced from a polymer such as
polyacrylonitrile (PAN), rayon, or petroleum pitch, known as a
precursor. For synthetic polymers such as PAN or rayon, the
precursor is first spun into filament yarns, using chemical and
mechanical processes to initially align the polymer molecules in a
way to enhance the final physical properties of the completed
carbon fiber. Precursor compositions and mechanical processes used
during spinning filament yarns may vary among manufacturers. After
drawing or spinning, the polymer filament yarns are then heated to
drive off non-carbon atoms (carbonization), producing the final
carbon fiber. The carbon fibers filament yarns may be further
treated to improve handling qualities, then wound on to
bobbins.
[0040] A common method of manufacture involves heating the spun PAN
filaments to approximately 300.degree. C. in air, which breaks many
of the hydrogen bonds and oxidizes the material. The oxidized PAN
is then placed into a furnace having an inert atmosphere of a gas
such as argon, and heated to approximately 2000.degree. C., which
induces graphitization of the material, changing the molecular bond
structure. When heated in the correct conditions, these chains bond
side-to-side (ladder polymers), forming narrow graphene sheets
which eventually merge to form a single, columnar filament. The
result is usually 93-95% carbon. Lower-quality fiber can be
manufactured using pitch or rayon as the precursor instead of PAN.
The carbon becomes further enhanced, as high modulus, or high
strength carbon, by heat treatment processes. Carbon heated in the
range of 1500-2000.degree. C. (carbonization) exhibits the highest
tensile strength (5,650 MPa, or 820,000 psi), while carbon fiber
heated from 2500 to 3000.degree. C. (graphitizing) exhibits a
higher modulus of elasticity (531 GPa, or 77,000,000 psi).
[0041] In some embodiments, commercially available carbon fiber
materials are use in the described compositions and methods (e.g.,
available from DowAksa, LLC (Istanbul, Turkey) and Toray (Tokyo,
Japan)). In some embodiments, carbon fibers for use herein comprise
filaments that are produced with fiber diameters of approximately 5
microns (e.g., plus or minus 5, 10, 15, or 20%). Examples include,
but are not limited to, T-700 fibers manufactured by Toray and A49
fibers manufactured by DowAksa.
[0042] In some embodiments, the fiber tube is impervious, permeable
(e.g., braided), or with controlled porosity (e.g., as shown in
FIG. 4), although the present disclosure is not limited to a
particular configuration. In some embodiments, at least a portion
of the fiber tube is configured to conform to the shape of the bone
cavity (e.g., by using a flexible material). In some embodiments,
at least a portion of the fiber tube is rigid enough to maintain a
shape (e.g., tube shape) after placement in the bone cavity. In
some embodiments, different segments of the fiber tube are
customized to have different levels of flexibility or porosity. In
this manner, the fiber tube can be customized to the shape of the
bone, the type of bone, and the type of repair or strengthening
desired.
[0043] In some embodiments, fiber angles in a braided tube are
optimized to create a compatible stiffness to that of the bone. By
designing and manipulating the angle of the fibers in the sleeve
with respect to the longitudinal axis of the bone this stiffness is
adjusted to match that of the bone. In some embodiments, this is
performed analytically and verified experimentally. In some
embodiments, the fiber tube and/or biocompatible polymer are
designed to resist compressive, torsional, and shear forces while
maintaining flexibility for healing and movement.
[0044] In addition to the excellent mechanical properties and
biocompatibility, carbon fiber has the added benefit of acting as
an antioxidant in the body. Carbon fibers have multiple advantages
in developing high-strength biomaterials with a density close to
bone for better stress transfer and electrical properties that
enhance tissue formation. Carbon-fiber-reinforced composite has
been shown to stimulate osseointegration inside the tibia bone
marrow measured as percent bone area (PBA) to a great extent when
compared to the titanium-6-4 alloy at statistically significant
levels.
[0045] In some embodiments, multiple layers (e.g., 1, 2, 3, 4, 5 or
more layers) of fiber (e.g., prepreg fiber) are implanted in the
bone cavity (e.g., to create enough strength and stiffness without
the need for the infill materials for repair and strengthening of
the bone).
[0046] In some embodiments, the carbon fiber tube is multi (e.g.,
two) layered. An Exemplary double layer tube, bag, or sleeve is
shown in FIG. 4. The right panel of FIG. 4 shows a double layered
sleeve. In some embodiments, the carbon fiber tube is a double
layer flexible bag where the outer sleeve (left panel of FIG. 4) is
in apposition with the host bone and has a porous (e.g., 10
.mu.m-200 .mu.m pores), e.g., cationic surface and the inner sleeve
(center panel of FIG. 4) is non-porous (e.g., <10 .mu.m pores)
and holds the injectable biocompatible polymer. The reduced
porosity of the inner sleeve of the carbon tube serves to contain
the polymer solution within the flexible bag and minimize any
leakage into the medullary cavity under pressure, and also to
minimize the infiltration of inflammatory cells like foreign body
giant cells, macrophages and osteoclasts that can result in
degradation of the polymeric implant.
[0047] In some embodiments, the carbon fiber tube has a diameter
between 5 mm to 45 mm.+-.1, 2, 3, 4, 5, or 10 mm. This size range
allows for insertion of the carbon fiber tube into the medullary
cavity of the bone, press-fit to the endosteal layer of the
medullary cavity of the bone, and allows the optimal amount of
polymer to be injected and to withstand the pressure and produce a
robust internal stabilization of the fracture. In some embodiments,
the size is altered to accommodate the medullary shaft of the bone,
as it varies based on the anatomic location (femur, tibia, radius,
ulna, clavicle, phalanges), age, sex, and disease conditions.
[0048] The present disclosure is exemplified with carbon fiber
tubes. However, the present disclosure is not limited to carbon
fiber tubes. Additional fibers (e.g., poly-paraphenylene
terephthalamide (Kevlar), polyethylene (Spectra), etc.) are also
suitable for use in the described compositions and methods.
[0049] In some embodiments, the systems and methods described
herein use a prepreg carbon fiber sleeve to support bone fragments.
Prepreg carbon fabric material is an ultrathin layer of carbon
fabric that is pre-impregnated with a resin system and kept at a
temperature below the service temperature. As long as this
temperature is maintained, the resin remains flexible and no curing
reaction occurs until the fabric temperature reaches a higher
temperature (e.g., service temperature). The difference between the
storage and service temperatures can be manipulated to fit a
special set of needs and parameters. For example, in some
embodiments, a prepreg sleeve is pre-impregnated and kept at
temperature of about 5 degrees Centigrade and then implanted in the
body where curing begins at body temperature. When the sleeve is
placed inside the bone cavity, it bonds to the inner surface of the
bone and bone fragments to form a solid load bearing structural
element.
[0050] In some embodiments, instead of a fiber, a filler material
comprising short chopped carbon or other fibers within the infill
matrix is used. In some embodiments, the chopped carbon fibers
comprise a "sizing" that matches the type of the infill polymer and
the carbon fiber to create a strong chemical bond between the two
materials.
[0051] In some embodiments, fiber tubes comprise sizing in order to
improve bonding with the polymer fill. Polyether and polyester
polyurethane dispersion based on aliphatic diisocyanates are often
used to formulate polyurethane carbon fiber sizing. Electroactive
Polymers (EAP) and Electrostrictive Graft Elastomers are non-liming
examples of products that are used as sizing in the compositions
and methods described herein. In some embodiments, the sizing on
the carbon fibers cross-links with the saturating resin or the
polymer infill materials to form a strong chemical bond.
[0052] In some embodiments, fiber tubes comprise surface
modification (e.g., of a layer of the carbon tube or sleeve that is
in contact with the host tissue). The surface modifications serve
to, for example, mitigate the risk of infection of the defect. In
some embodiments, this is achieved by modifying or functionalizing
the outer surface of the carbon fiber with antimicrobial coatings
or attaching antimicrobial agents to modified surfaces.
[0053] The present disclosure is not limited to particular surface
coatings or treatments. Examples include but are not limited to,
modification by electrochemical, chemical, thermal, discharge
plasma, radiation treatment. In some embodiments, modification of
the surface of the carbon fiber increases the wettability of the
fiber surface by the matrix resin and increases interaction with
the host body fluid. This increases roughness, which promotes more
surface area on the fiber, and improves interactions between matrix
resin and the host tissue. In some embodiments, surface
modification and the porosity of the carbon tube promotes
mechanical interlocking between the fiber and the host tissue and
increases the number of active sites on the fiber surface for
subsequent chemical bonding. For example, in some embodiments,
surface treatment by chemical, plasma or radiation leads to
oxidation of the surface and increases active groups (e.g.,
carboxyl, carbonyl, ester, lactone, enol and quinone), leading to
enhanced chemical bonding with the matrix resin or host tissue.
This also allows one to functionalize the carbon surface by
crosslinking/grafting/co-polymerizing antimicrobial molecules or
biomolecules for, for example, preventing infection and or improved
osseointegration.
[0054] The surface modification of the outer layer of the carbon
tube increases the active sites (e.g., functional groups) for
coating/grafting/crosslinking of antimicrobial molecules or
compounds. The use of cationic carbon fiber in bone further
prevents infection of the implant site without using antibiotics or
sensitizing the microbes to become resistant.
[0055] Surface modified carbon increases the presence of functional
groups like carboxyl (COOH), carbonyl (C.dbd.O), ester (COO),
lactone or cyclic carboxylic esters (--(C.dbd.O)--O--). In some
embodiments, these functional groups are used to crosslink
quaternary ammonium and other cationic salts via electrostatic
binding or covalent crosslinking via alkylation. In some
embodiments, agents are grafted using cationic photoinitiators and
UV photopolymerization on to the surface of the carbon fiber. The
design and development of antimicrobial carbon surface is not
limited to quaternary ammonium, as other compounds such as metal
based antimicrobials (e.g., silver, bismuth), polymer-based
antimicrobials (e.g., polyhexamethylene biguanide-PHMB) and
oxidizing agents (e.g., hydrogen peroxide) may be used. These
cationic compounds are FDA approved and are used widely in wound
dressings.
[0056] The present disclosure is not limited to particular polymer
materials for use in filling the fiber tube or sleeve. Examples of
biocompatible polymers include, but are not limited to, calcium
phosphate, poly(lactic-co-glycolic) acid, polyanhydrides,
polyvinylchloride (PVC), polyethylene (PE), polypropylene (PP),
polymethylmetacrylate (PMMA), polystyrene (PS),
polytetrafluoroethylene (PTFE), polyurethane (PU), polyamide
(nylon), polyethylenterephthalate (PET), polyethersulfone (PES),
polycarbonates (PC), polyetherimide (PEI) (See e.g., Pandey et al.,
IJPSR, 2016; Vol. 7(7):2748-2755), polycaprolactone (PCL), or
mineralized bone particles (MBP).
[0057] In some embodiments, polymerization of the biocompatible
polymer occurs in situ. For example, in some embodiments, the
delivery system comprises photocurable or photocrosslinkable
polymers that are degradable or non-degradable. The
photocrosslinking is not limited to UV and also includes visible,
near IR (NIR), IR and other ranges. Photocurable or
photocrosslinkable polymers can be synthesized or commercially
obtained. In some embodiments, multifunctional monomers bearing
cleavable linkage of the polymer are UV cured in the presence of a
photoinitator (e.g., Irgacure 2959 (274 nm), or Darcocure (295 nm).
The polymerizing unit may contain and not limited to methacrylate,
acrylate, epoxy units etc. Cleavable units include but are not
limited to, acetal, hemiacetal, ester, carboxylate, carbonate, and
thiol.
[0058] Carbon fibers are not UV transparent, which is challenging
for using UV curing resins with carbon fiber patches. To solve this
problem, cationic polymerization is useful because of continued
dark polymerization after UV absorption. Examples include but are
not limited to cationic photoinitators (e.g., aryl iodonium salts,
triphenyl sulfonium, diazonium, ferrocenium etc.). Cationic
polymerization allows for tighter control of the molecular weight
comparted to free radical polymerization and exhibits a very low
shrink rate and provide robust implant stability.
[0059] In some embodiments, polymer infill materials have high
compression, but weak tension. Typically, the tensile strength of
polymer fillers is about 10% to 20% of their compressive strength;
therefore, in some embodiments, inner reinforcement is used for the
fillers to create a balanced design. In some embodiments, in order
to improve the tensile strength of the filler, the filler is
pre-compressed before any load is applied. In this manner, the
pre-compressive stresses negate the tensile stresses resulting from
the applied loads due to shear and torsional forces, as shown in
FIG. 2. The pre-compression is achieved by applying a tension force
to the carbon fiber while the infill paste is in a liquid state and
releasing that tension force as soon as the infill polymer material
is set. The reaction from the release translates into a permanent
compression force on the paste as shown in FIG. 2.
[0060] There are three types of stresses that the bone is subjected
to after treatment: compressive stresses, tensile stresses due to
bending and tensile stresses due to torsion. In some embodiments,
the tensile stresses are compensated for either by pre-compression
or by the use of an internal scaffold of carbon fiber, as shown in
FIG. 3(b).
[0061] In some embodiments, the polymer is an expansive polymer
that expands in bone cavity, providing compressive stresses and
aiding in bonding the polymer to the bone and/or fiber sleeve.
[0062] In some embodiments, an alternative to including internal
scaffolding reinforcement in the carbon sleeve is to insert a
flexible, spring like carbon fiber spiral reinforcement as shown in
FIG. 3(a) to increase the capacity of the infill material to resist
tensile stresses developed as a result of shear and torsional
forces, as shown in the figure.
[0063] In some embodiments, implants comprise small fibers mixed
with the polymer prior to injection into the bone. Mixing small
fibers (e.g., carbon fibers, carbon nanoparticles, etc.) with the
polymer significantly enhances the tensile strength of the
compound. In some embodiments, this eliminates the need for a
carbon sleeve or membrane. In some embodiments, such implants are
combined with carbon fiber sleeves, bags, or tubes.
[0064] In some embodiments, the fiber component and/or the
biocompatible polymer comprise one or more additional components.
For example, in some embodiments, drugs (e.g., antibiotics, agents
that promote bone healing such as growth factor, or
chemotherapeutic agents) or bone precursors (e.g., osteoblasts
and/or osteoclasts) are incorporated into the carbon fiber or
biocompatible polymer.
[0065] In some embodiments, fiber components (e.g., tubes) and/or
biocompatible polymer components are designed to change properties
with electrical, chemical, temperature, or UV stimulation. For
example, in some embodiments, outside or intrinsic stimuli are used
to adjust the mechanical properties of the fiber or polymer
component and/or release a component (e.g., antibiotic) or soften
the polymer for removal.
[0066] As described herein, in some embodiments, the compositions
of the present disclosure are removable. For example, in some
embodiments, an injectable delivery system comprising biocompatible
gold nanoparticles are injected and heated using radio frequency
waves (RF) or contain degradable crosslinkers that are labile to
UV, thermal, organic solvents or enzymes that can be safely
degraded and liquified are used. The depolymerized polymerized
implant along with the carbon sleeve are then effectively removed
from the medullary shaft of the bone.
[0067] In some embodiments, gold nanoparticles for implant removal
are heated using shortwave RF fields, which is non-invasive to the
human body, has full-body penetration, and has been extensively
studied for in situ cancer ablation and drug delivery systems. In
some embodiments gold nanoparticles (GNp) have a diameter of 1
nm-100 nm and are mixed within the monomer to obtain a homogeneous
dispersion prior to polymerization. The gold nanoparticles may be
used with or without surface modification. To depolymerize the
implant, RF waves in the operating frequency (e.g., ranging between
13.56 MHz-50 GHz and an operating power of 200 W) are used. The
gold nanoparticles are nontoxic to be body and are well tolerated.
They have a low reticulo endothelial (RER) clearance rate and hence
stay within the liquified polymer system for safe removal.
[0068] In some embodiments, removal methods utilize the
incorporation of photolabile crosslinkers including but not limited
to, 1,4-diacetylbenzene 1,4-bis(O-methacryloyl)dioxime and
1,3,5-triacetylbenzene 1,3,5-tris(O-methacryloyl)trioxime) mixed
with the injectable polymer system. Such crosslinkers are UV
depolymerized within the carbon sleeve and then are removed.
[0069] In some embodiments, the fiber tubes and biocompatible
polymers are provided as a kit or system (e.g., comprising a fiber
tube material described herein and optionally a biocompatible
polymer). In some embodiments, kits and systems further comprise
one or more components useful, necessary, or sufficient to perform
the described methods (e.g., including but not limited to, guide
wires, additional reinforcing materials, removal components, and
the like).
[0070] The systems and method of the disclosure find use in the
treatment of fractures in any bones with fractures amendable to
treatment with the disclosed systems and kits. Examples include,
but are not limited to, clavicle, radius, ulna, hip, femur, tibia,
and fibula. The systems and methods described herein find use in
the treatment of a variety of types of fractures including, but not
limited to, stable fractures, open, compound fractures, transverse
fractures, oblique fractures, and comminuted fractures.
[0071] The systems and methods described herein further find use in
strengthening bones in subjects at an increased risk of fractures
(e.g., subjects with overuse, injury, cancer, osteoporosis or other
disorders). Thus, in subject embodiments, the systems and methods
are used to prevent, rather than treat, fractures. In some
embodiments, bone strengthening applications provide a permanent
fix for weak bones.
[0072] The systems and methods described herein find use in the
treatment and prevention of fractures in any number of subjects. In
some embodiments, the subject is a human. In other, embodiments,
the subject is a non-human animal. For example, in some
embodiments, the subject is an equine (e.g., racehorse) or
companion animal (e.g., dog or cat), although additional subjects
are specifically contemplated.
EXAMPLES
[0073] The following examples are included to demonstrate certain
embodiments of the invention. It should be appreciated by those of
skill in the art that the techniques disclosed in the examples
which follow represent techniques discovered by the inventors to
function well in the practice of the invention, and thus are
considered to constitute certain aspects for its practice. However,
those of skill in the art should, in light of the present
disclosure, appreciate that many changes can be made in the
specific embodiments which are disclosed and still obtain a like or
similar result without departing from the spirit and scope of the
invention.
Example 1
Fixation of a Fractured Humerus in a Human Patient
[0074] The following example describes treatment strategies for a
fractured humerus involving a treatment method of embodiments of
the present invention.
[0075] A 25 year old human male patient presents with a fractured
humerus. The bone was broken in an automobile accident. He visits a
physician and undergoes x-ray imaging. He is diagnosed with a
compound fracture of the right humerus. The physician recommends
minimally invasive fixation using an intramedullary carbon fiber
tube. The patient is sedated and treated with a bone repair system
described herein. During his follow up visit with his physician,
the patient undergoes additional x-ray imaging which shows that the
bone is healing. The patient continues to improve and regains full
use of the right arm within 3 months. No side effects are
reported.
Example 2
Reinforcement of a Hip Bone in a Patient with Osteoporosis
[0076] The following example describes treatment strategies for
strengthening of a hip bone involving reinforcement with a carbon
fiber tube of embodiments of the present invention. A 71 year old
woman is diagnosed with severe osteoporosis. A physician treats the
woman with a bone strengthening repair system described herein. The
patient continues to improve and is able to walk normally within 3
months. No side effects are reported.
Example 3
Fixation of Fractured Equine Tibia
[0077] The following example describes a treatment strategy for an
equine with a fractured tibia involving implantation of a carbon
fiber tube of embodiments of the present invention.
[0078] A 3 year old male racehorse presents with a weakness in the
left foreleg. A veterinary surgeon diagnoses the horse with a
fractured tibia. The surgeon repairs the bone with a bone repair
system described herein. The horse continues to improve and is
functioning normally at 4 months. No side effects are reported.
Example 4
Fixation of Fractured Equine Pelvis
[0079] The following example describes a treatment strategy for an
equine with a fractured pelvis involving implantation of a carbon
fiber tube of embodiments of the present invention.
[0080] A 5 year old female workhorse presents with lameness. A
veterinary surgeon diagnoses the horse with a fractured pelvis. The
surgeon treats the fracture with a bone repair system described
herein. The horse continues to improve and is functioning normally
at 6 months. No side effects are reported.
[0081] All publications and patents mentioned in the above
specification are herein incorporated by reference as if expressly
set forth herein. Various modifications and variations of the
described methods and compositions of the invention will be
apparent to those skilled in the art without departing from the
scope and spirit of the invention. Although the invention has been
described in connection with specific preferred embodiments, it
should be understood that the invention as claimed should not be
unduly limited to such specific embodiments. Indeed, various
modifications of the described modes for carrying out the invention
that are obvious to those skilled in relevant fields are intended
to be within the scope of the invention.
* * * * *