U.S. patent application number 14/329123 was filed with the patent office on 2015-01-22 for lubricious, biocompatible hydrophilic thermoset coating using interpenetrating hydrogel networks.
The applicant listed for this patent is Cardiac Pacemakers, Inc.. Invention is credited to Adegbola O. Adenusi, Joseph T. Delaney, JR., Jeannette C. Polkinghorne, Kasyap Seethamraju, David R. Wulfman.
Application Number | 20150025608 14/329123 |
Document ID | / |
Family ID | 52344181 |
Filed Date | 2015-01-22 |
United States Patent
Application |
20150025608 |
Kind Code |
A1 |
Delaney, JR.; Joseph T. ; et
al. |
January 22, 2015 |
LUBRICIOUS, BIOCOMPATIBLE HYDROPHILIC THERMOSET COATING USING
INTERPENETRATING HYDROGEL NETWORKS
Abstract
A medical electrical lead includes an insulative lead body
extending from a distal region to a proximal region and a conductor
disposed within the insulative lead body and extending from the
proximal region to the distal region. An electrode is disposed on
the insulative lead body and is in electrical contact with the
conductor. The medical electrical lead also includes a cross-linked
hydrophilic polymer coating disposed over at least a portion of the
electrode. The cross-linked hydrophilic polymer coating includes a
fibrous matrix comprising a plurality of discrete fibers and pores
formed between at least a portion of the fibers and a hydrophilic
polyethylene glycol-containing hydrogel network disposed within the
pores of the fibrous matrix.
Inventors: |
Delaney, JR.; Joseph T.;
(Minneapolis, MN) ; Polkinghorne; Jeannette C.;
(Spring Lake Park, MN) ; Adenusi; Adegbola O.;
(Burnsville, MN) ; Wulfman; David R.;
(Minneapolis, MN) ; Seethamraju; Kasyap; (Eden
Prairie, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Cardiac Pacemakers, Inc. |
St. Paul |
MN |
US |
|
|
Family ID: |
52344181 |
Appl. No.: |
14/329123 |
Filed: |
July 11, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61856959 |
Jul 22, 2013 |
|
|
|
Current U.S.
Class: |
607/116 ;
264/465; 264/555; 427/2.24 |
Current CPC
Class: |
A61N 1/0534 20130101;
D01D 5/0023 20130101; A61N 1/0551 20130101; A61N 1/056 20130101;
D01D 5/0007 20130101; A61N 1/05 20130101; A61N 1/0541 20130101;
A61N 1/0543 20130101; Y10T 29/49982 20150115 |
Class at
Publication: |
607/116 ;
427/2.24; 264/465; 264/555 |
International
Class: |
H01B 7/04 20060101
H01B007/04; D01D 5/00 20060101 D01D005/00; H01B 13/32 20060101
H01B013/32; A61N 1/05 20060101 A61N001/05; H01B 13/16 20060101
H01B013/16 |
Claims
1. A medical electrical lead comprising: an insulative lead body
extending from a distal region to a proximal region; a conductor
disposed within the insulative lead body and extending from the
proximal region to the distal region; an electrode disposed on the
insulative lead body and in electrical contact with the conductor;
and a cross-linked hydrophilic polymer coating disposed over at
least a portion of the electrode, the cross-linked hydrophilic
polymer coating comprising: a fibrous matrix comprising a plurality
of discrete fibers and pores formed between at least a portion of
the fibers; and a hydrophilic polyethylene glycol-containing
hydrogel network disposed within the pores of the fibrous
matrix.
2. The medical electrical lead of claim 1, wherein the fibers of
the fibrous matrix comprise a fluoropolymer.
3. The medical electrical lead of claim 2, wherein the fibers of
the fibrous matrix comprise a poly(vinylidene
fluoride-co-hexafluoropropene) (PVDF HFP) polymer.
4. The medical electrical lead of claim 1, wherein the fibers of
the fibrous matrix comprise a poly(styrene-isobutylene-styrene)
(SIBS) tri-block polymer.
5. The medical electrical lead of claim 1, wherein the fibers of
the fibrous matrix comprise one of a polyurethane, polycarbonate,
polyether, polyester and a polyisobutylene (PIB) polymer.
6. The medical electrical lead of claim 1, wherein the fibrous
matrix is a nonwoven fibrous matrix.
7. The medical electrical lead of claim 1, wherein the fibrous
matrix is an electrospun fibrous matrix.
8. The medical electrical lead of claim 1, wherein the hydrophilic
polyethylene glycol-containing hydrogel comprises a polyethylene
glycol (PEG) having a number molecular weight (M.sub.N) range of
about 400 g/mol to about 5,000 g/mol.
9. The medical electrical lead of claim 1, wherein the hydrophilic
polyethylene glycol-containing hydrogel comprises a polyethylene
glycol (PEG) having a number molecular weight (M.sub.N) range of
about 5,000 g/mol to about 30,000 g/mol.
10. The medical electrical lead of claim 1, wherein the hydrophilic
polyethylene glycol-containing hydrogel network is disposed within
at least a portion of the pores of the fibrous matrix, the pores
forming a network that extends from a first surface of the fibrous
matrix to a second surface of the fibrous matrix which is opposite
the first surface.
11. A medical electrical lead comprising: an insulative lead body
extending from a distal region to a proximal region; a conductor
disposed within the insulative lead body and extending from the
proximal region to the distal region; an electrode disposed on the
insulative lead body and in electrical contact with the conductor;
and a cross-linked hydrophilic polymer coating disposed over at
least a portion of the lead body, the cross-linked hydrophilic
polymer coating comprising: a fibrous matrix comprising a plurality
of discrete fibers and pores formed between at least a portion of
the fibers; and a hydrophilic polyethylene glycol-containing
hydrogel network disposed within the pores of the fibrous
matrix.
12. A method of forming a cross-linked hydrophilic coating on an
implantable medical electrical lead having an insulative lead body
and an electrode disposed on the insulative lead body, the method
comprising: disposing within at least a portion of pores of a
nonwoven fibrous matrix a hydrogel comprising at least one
polyethylene glycol containing polymer, such that the hydrogel
continuously extends from a first surface to an opposite second
surface of the nonwoven fibrous matrix; and curing the hydrogel to
the nonwoven fibrous matrix to form the cross-linked hydrophilic
coating.
13. The method of claim 12, wherein the hydrogel is cured using one
of a thermoinitiator and a photoinitiator curing initiator.
14. The method of claim 13, wherein the hydrogel is cured using
benzoyl peroxide.
15. The method of claim 12, further comprising forming the nonwoven
fibrous matrix by using one of an electrospinning process and a
melt blowing process.
16. The method of claim 12, further comprising plasma treating the
nonwoven fibrous matrix prior to applying the hydrogel to the
nonwoven fibrous matrix.
17. The method of claim 12, further comprising disposing the
hydrogel within at least a portion of the pores by one of dip
coating, roll coating, spray coating, drop coating, and flow
coating.
18. The method of claim 12, further comprising disposing the
cross-linked hydrophilic coating onto the electrode.
19. The method of claim 18, further comprising disposing the
cross-linked hydrophilic coating onto the electrode before the
electrode is assembled onto the implantable medical electrical
lead.
20. The method of claim 12, further disposing within at least a
portion of pores of a nonwoven fibrous matrix the hydrogel such
that the hydrogel covers at least a portion of the surfaces of
fibers of the nonwoven fibrous matrix.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional
Application 61/856,959, filed Jul. 22, 2013, which is herein
incorporated by reference in its entirety.
TECHNICAL FIELD
[0002] The present invention relates to medical devices and methods
for manufacturing medical devices. More specifically, the invention
relates to coated medical electrical leads and to methods for
coating medical electrical leads.
BACKGROUND
[0003] Cardiac pacing leads are well known and widely employed for
carrying pulse stimulation signals to the heart from a battery
operated pacemaker, or other pulse generating means, as well as for
monitoring electrical activity of the heart from a location outside
of the body. Electrical energy is applied to the heart via an
electrode to return the heart to normal rhythm. Some factors that
affect electrode performance include polarization at the
electrode/tissue interface, electrode capacitance, sensing
impedance, and voltage threshold. In all of these applications, it
is highly desirable to optimize electrical performance
characteristics at the electrode/tissue interface.
[0004] A recognized performance challenge of materials
conventionally used as electrodes includes the difficulty of
controlling tissue in-growth while optimizing the lead performance
characteristics at the electrode/tissue interface. This challenge
may result in a lead having lower than ideal electrical performance
characteristics, which may further reduce over time.
SUMMARY
[0005] Disclosed herein are various embodiments of coated medical
electrical leads and methods for coating medical electrical
leads.
[0006] In Example 1, a medical electrical lead includes an
insulative lead body extending from a distal region to a proximal
region and a conductor disposed within the insulative lead body and
extending from the proximal region to the distal region. An
electrode is disposed on the insulative lead body and in electrical
contact with the conductor. A cross-linked hydrophilic polymer
coating is disposed over at least a portion of the electrode. The
cross-linked hydrophilic polymer coating includes a fibrous matrix
comprising a plurality of discrete fibers and pores formed between
at least a portion of the fibers and a hydrophilic polyethylene
glycol-containing hydrogel network disposed within the pores of the
fibrous matrix.
[0007] In Example 2, the medical electrical lead according to
Example 1, wherein the fibers of the fibrous matrix include a
fluoropolymer.
[0008] In Example 3, the medical electrical lead according to
Example 1 or 2, wherein the fibers of the fibrous matrix include a
poly(vinylidene fluoride-co-hexafluoropropene) (PVDF HFP)
polymer.
[0009] In Example 4, the medical electrical lead according to any
of Examples 1-3, wherein the fibers of the fibrous matrix include a
poly(styrene-isobutylene-styrene) (SIBS) tri-block polymer.
[0010] In Example 5, the medical electrical lead according to any
of Examples 1-4, wherein the fibers of the fibrous matrix include a
polycarbonate, polyether, polyester or a polyisobutylene (PIB)
polymer.
[0011] In Example 6, the medical electrical lead according to any
of Examples 1-5, wherein the fibrous matrix is a nonwoven fibrous
matrix.
[0012] In Example 7, the medical electrical lead according to any
of Examples 1-6, wherein the fibrous matrix is an electrospun
fibrous matrix.
[0013] In Example 8, the medical electrical lead according to any
of Examples 1-7, wherein the hydrophilic polyethylene
glycol-containing hydrogel includes a polyethylene glycol (PEG)
having a number molecular weight (MN) range of about 400 g/mol to
about 5,000 g/mol.
[0014] In Example 9, the medical electrical lead according to any
of Examples 1-8, wherein the hydrophilic polyethylene
glycol-containing hydrogel includes a polyethylene glycol (PEG)
having a number molecular weight (MN) range of about 5,000 g/mol to
about 30,000 g/mol.
[0015] In Example 10, the medical electrical lead according to any
of Examples 1-9, wherein the hydrophilic polyethylene
glycol-containing hydrogel network is disposed within at least a
portion of the pores of the fibrous matrix. The pores form a
network that extends from a first surface of the fibrous matrix to
a second surface of the fibrous matrix which is opposite the first
surface.
[0016] In Example 11, a medical electrical lead includes an
insulative lead body extending from a distal region to a proximal
region and a conductor disposed within the insulative lead body and
extending from the proximal region to the distal region. An
electrode is disposed on the insulative lead body and in electrical
contact with the conductor. A cross-linked hydrophilic polymer
coating is disposed over at least a portion of the lead body. The
cross-linked hydrophilic polymer coating includes a fibrous matrix
comprising a plurality of discrete fibers and pores formed between
at least a portion of the fibers and a hydrophilic polyethylene
glycol-containing hydrogel network disposed within the pores of the
fibrous matrix.
[0017] In Example 12, a method of forming a cross-linked
hydrophilic coating on an implantable medical electrical lead
having an insulative lead body and an electrode disposed on the
insulative lead body. The method includes disposing within at least
a portion of pores of the a nonwoven fibrous matrix a hydrogel
comprising at least one polyethylene glycol containing polymer,
such that the hydrogel continuously extends from a first surface to
an opposite second surface of the nonwoven fibrous matrix. The
method also includes curing the hydrogel to the nonwoven fibrous
matrix to form the cross-linked hydrophilic coating.
[0018] In Example 13, the medical electrical lead according to
Example 12, wherein the hydrogel is cured using one of a
thermoinitiator and a photoinitiator curing initiator.
[0019] In Example 14, the medical electrical lead according to
Example 12 or 13, wherein the hydrogel is cured using benzoyl
peroxide.
[0020] In Example 15, the medical electrical lead according to any
of Examples 12-14, further including forming the nonwoven fibrous
matrix by using one of an electrospinning process and a melt
blowing process.
[0021] In Example 16, the medical electrical lead according to any
of Examples 12-15, further including plasma treating the nonwoven
fibrous matrix prior to applying the hydrogel to the nonwoven
fibrous matrix.
[0022] In Example 17, the medical electrical lead according to any
of Examples 12-16, further includes disposing the hydrogel within
at least a portion of the pores by one of dip coating, roll
coating, spray coating, drop coating, and flow coating.
[0023] In Example 18, the medical electrical lead according to any
of the Examples 12-17, further includes disposing the cross-linked
hydrophilic coating onto the electrode.
[0024] In Example 19, the medical electrical lead according to any
of the Examples 12-18, further includes disposing the cross-linked
hydrophilic coating onto the electrode before the electrode is
assembled onto the implantable medical electrical lead.
[0025] In Example 20, the medical electrical lead according to any
of the Examples 12-19, further includes disposing within at least a
portion of pores of a nonwoven fibrous matrix the hydrogel such
that the hydrogel covers at least a portion of the surfaces of
fibers of the nonwoven fibrous matrix.
[0026] While multiple embodiments are disclosed, still other
embodiments of the present invention will become apparent to those
skilled in the art from the following detailed description, which
shows and describes illustrative embodiments of the invention.
Accordingly, the drawings and detailed description are to be
regarded as illustrative in nature and not restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a schematic view of a medical electrical lead
according to embodiments of the present invention.
[0028] FIGS. 2A and 2B are schematic longitudinal cross-sections of
a medical electrical lead according to embodiments of the present
invention.
[0029] FIG. 3 is a schematic illustration of a cross-linked
hydrophilic polymer coating.
[0030] FIG. 4 is an image of a water droplet on the surface of an
exemplary uncoated fibrous matrix.
[0031] FIG. 5 is an image of a water droplet on the surface of an
exemplary cross-linked hydrophilic polymer coating.
[0032] FIG. 6 is a light microscope image of a polyvinylidene
fluoride (PVDF) fibrous matrix.
[0033] FIG. 7 is a confocal microscope image of a cross-linked
hydrophilic polymer coating including a polyethylene glycol (PEG)
hydrogel and a PVDF fibrous matrix.
[0034] While the invention is amenable to various modifications and
alternative forms, specific embodiments have been shown by way of
example in the drawings and are described in detail below. The
intention, however, is not to limit the invention to the particular
embodiments described. On the contrary, the invention is intended
to cover all modifications, equivalents, and alternatives falling
within the scope of the invention as defined by the appended
claims.
DETAILED DESCRIPTION
[0035] FIG. 1 is a partial cross-sectional view of a medical
electrical lead 10, according to various embodiments of the present
disclosure. According to some embodiments, the medical electrical
lead 10 can be configured for implantation within a patient's
heart. According to other embodiments, the medical electrical lead
10 is configured for implantation within a patient's neurovascular
regions. In yet another embodiment, the lead 10 can be a lead 10
for a cochlear implant. Thus, the electrical lead 10 can be used
for a wide range of medical applications that deliver an electrical
shock or pulse.
[0036] The medical electrical lead 10 includes an elongated,
insulative lead body 12 extending from a proximal end 16 to a
distal end 20. The proximal end 16 is configured to be operatively
connected to a pulse generator (not shown) via a connector 24. At
least one conductor 32 extends from the connector 24 at the
proximal end 16 of the lead 10 to one or more electrodes 28 at the
distal end 20 of the lead 10. The conductor 32 can be a coiled or
cable conductor. According to some embodiments where multiple
conductors 32 are employed, the lead 10 can include a combination
of coiled and cable conductors 32. When a coiled conductor 32 is
employed, according to some embodiments, the conductor 32 can have
either a co-radial or a co-axial configuration.
[0037] The lead body 12 is flexible, but substantially
non-compressible along its length, and has a suitable
cross-sectional shape. For example, lead body 12 may have a
generally circular cross-sectional shape. The lead body 12 may be
of a suitable size for implantation. For example, an outer diameter
of the lead body 12 may range from about 2 to about 15 French. The
lead body 12 may include a suitable bio-compatible, electrically
insulative material. For example, in some embodiments, the lead
body 12 may include silicone or polyurethane. In some embodiments,
the lead body 12 may have a substantially uniform composition along
its length. In other embodiments, the composition of the lead body
12 may vary in any direction, including along the length and/or
thickness.
[0038] The medical electrical lead 10 can be unipolar, bipolar, or
multi-polar depending upon the type of therapy to be delivered. In
some embodiments of the present disclosure employing multiple
electrodes 28 and multiple conductors 32, each conductor 32 is
adapted to be connected to an individual electrode 28 in a
one-to-one manner allowing each electrode 28 to be individually
addressable. Additionally, the lead body 12 can include one or more
lumens adapted to receive a guiding element such as a guidewire or
a stylet for delivery of the lead 10 to a target location within a
patient's heart.
[0039] The electrodes 28 can have any electrode 28 configuration as
is known in the art. According to one embodiment of the present
disclosure, at least one electrode 28 can be a ring or partial ring
electrode 28. According to another embodiment, at least one
electrode 28 is a shocking coil. According to yet another
embodiment of the present disclosure, at least one electrode 28
includes an exposed electrode 28 portion and an insulated electrode
28 portion. In some embodiments, a combination of electrode 28
configurations can be used. The electrodes 28 can be coated with or
formed from platinum, stainless steel, titanium, tantalum,
palladium, MP35N, other similar conductive material, alloys of any
of the foregoing including platinum-iridium alloys, and other
combinations of the foregoing including clad metal layers or
multiple metal materials.
[0040] According to various embodiments, the lead body 12 can
include one or more fixation members (not shown) for securing and
stabilizing the lead body 12 including the one or more electrodes
28 at a target site within a patient's body. The fixation member(s)
can be active or passive. An exemplary active fixation member
includes a screw-in fixation member. Examples of passive fixation
members can include pre-formed distal portions of the lead body 12
adapted to bear against vessel walls and/or expandable tines
provided at the distal end 20 of the lead body 12.
[0041] The lead 10 includes a cross-linked hydrophilic polymer
coating 40 that is disposed over various parts of the insulative
lead body 12. FIGS. 2A and 2B are schematic longitudinal
cross-sectional views of the lead 10 of FIG. 1, in which internal
structure has been removed for clarity, and provide illustrative
but non-limiting examples of regions of the lead 10 that may
include a cross-linked hydrophilic polymer coating 40.
[0042] FIG. 2A shows the cross-linked hydrophilic polymer coating
40 disposed over at least a portion of the insulative lead body 12.
The cross-linked hydrophilic polymer coating 40 includes a first
surface 42 and a second opposite surface 44. The illustrated
portion of the insulative lead body 12 may be adjacent an electrode
28, or it may be spaced apart from the electrode 28.
[0043] In contrast, FIG. 2B illustrates the cross-linked
hydrophilic polymer coating 40 disposed over the electrode 28.
While the cross-linked hydrophilic polymer coating 40 is
illustrated as entirely covering the electrode 28, in some
embodiments the cross-linked hydrophilic polymer coating 40 may
cover only a portion of the electrode 28. For example, the
cross-linked hydrophilic polymer coating 40 may cover a majority or
a minority portion of the electrode 28. In some embodiments, the
coating 40 may cover any portion of the electrode 28, such as at
least one of the ends or at least one of the intermediate portions
of the electrode 28.
[0044] The cross-linked hydrophilic polymer coating 40 may be of
any suitable thickness that delivers electrophysiological therapy
through the polymer coating 40. For example, the cross-linked
hydrophilic polymer coating 40 may have a thickness in the range of
about 500 nanometer (nm) to 300 microns. A suitable coating
thickness range also includes the range of about 15 microns to 250
microns, for example. In other examples, the average coating
thickness of the cross-linked hydrophilic polymer coating 40 may be
about 90 microns (or 0.0035 inches).
[0045] In some embodiments, the cross-linked hydrophilic polymer
coating 40 may be formed directly on a portion of the lead 10, such
as the lead body 12, for example, after the lead 10 is assembled.
Alternatively, the cross-linked hydrophilic polymer coating 40 may
be formed directly on a component of the lead 10, such as on the
electrode 28, for example, before the lead 10 is assembled. In some
embodiments, the cross-linked hydrophilic polymer coating 40 may be
formed separately on a substrate and then subsequently disposed
onto a portion of the lead 10, either before or after assembly of
the lead 10. For example, the cross-linked hydrophilic coating 40
may be formed on a substrate as a thin film and then subsequently
transferred from the substrate to be disposed on a portion of the
lead 10 during the lead assembly.
[0046] The cross-linked hydrophilic polymer coating 40 may provide
one or more beneficial functionalities to the lead 10. In some
embodiments, the cross-linked hydrophilic polymer coating 40 may
improve the electrical conductivity of the lead 10. In certain
embodiments, the cross-linked hydrophilic polymer coating 40 may
increase the impedance of the lead 10. In other embodiments, the
cross-linked hydrophilic polymer coating 40 may minimize cellular
in-growth and prevent tissue attachment to the lead 10. In yet
other embodiments, the cross-linked hydrophilic polymer coating 40
may provide a bio-stable surface for a least a portion of the lead
10.
[0047] FIG. 3 shows an illustrative, but non-limiting example of a
cross-linked hydrophilic polymer coating 40 including a fibrous
matrix 50 and a hydrophilic hydrogel 52. The fibrous matrix 50 is a
structure comprising a plurality of discrete fibers 56. As shown in
FIG. 3, the hydrogel 52 is a network of hydrophilic polymer chains
located between the fibers 56 of the fibrous matrix 50.
Hydrophilicity (also termed as wettability) characterizes the
ability of a surface to absorb a liquid, such as water. In
contrast, hydrophobicity characterizes an inability of a surface to
absorb a liquid, otherwise described as the ability of a surface to
repel a liquid, such as water.
[0048] The fibrous matrix 50 includes fibers 56 that overlap with
one another to create pores 54, or spaces, between a given fiber 56
and one or more neighboring fibers 56. The pores 54 may be formed
between neighboring fibers 56 in any direction, including along the
length, width and thickness of the fibrous matrix 50. The pores 54
of the fibrous matrix 50 may vary in shape and size. The pores 54
may be interconnected with other pores 54 within the matrix 50. In
some embodiments, the pores 54 create a continuous porous network
within the matrix 50. In some embodiments, the pores 54 create a
continuous porous network from the first surface 42 of the fibrous
matrix 50 to the second opposite surface 44 of the fibrous matrix
50 (see FIGS. 2A and 2B). In certain embodiments, the plurality of
pores 54 created by the fibers 56 may extend through the matrix 50
in all three spatial directions (i.e., in the x, y, z
directions).
[0049] In some embodiments, as shown in FIG. 3, the fibrous matrix
50 may be a nonwoven matrix. For example, the fibrous matrix 50 may
comprise a plurality of randomly aligned fibers 56 in certain
embodiments. As further described herein, a randomly aligned
fibrous matrix 50 may be formed by various methods that include,
for example, blow melting and electrospinning. In other
embodiments, the fibrous matrix 50 may be a woven matrix in which
the fibers 56 are oriented in a repeating pattern or
configuration.
[0050] The fibers 56 of the fibrous matrix 50 may have diameters in
the range of about 100 nanometer (nm) to 10,000 nm, for example.
The fiber diameter size may be about 100 nm to 3,000 nm, for
example. Suitable fiber diameter sizes also include about 40 nm to
2,000 nm, about 100 nm to 1,500 nm or about 100 nm to 1,000 nm, for
example. In still further examples, the fiber diameter may be 100
nm to 800 nm, or 100 nm to 400 nm. In other examples, the average
fiber diameter may be 400 nm to 10 microns or 800 nm to 10
microns.
[0051] As mentioned previously herein, the fibers 56 within the
fibrous matrix 50 can create pores 54 of varying sizes within the
matrix 50. Fiber configuration and diameter may affect average pore
size and range of the pore size of the pores 54 within the matrix
50. For example, a nonwoven fibrous matrix 50 having fibers 56 with
a diameter ranging between 0.2-1.0 microns may produce a matrix 50
having a pore size range between 1 nm and 0.5 microns.
[0052] Suitable materials for the fibers 56 of the fibrous matrix
50 include both conductive and non-conductive polymer materials. In
some embodiments, the fibers 56 of the fibrous matrix 50 are formed
from a fluoropolymer material. Suitable fluoropolymer materials for
the fibers 56 may include polyvinylidene fluoride (PVDF) and
poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP). Other
examples of suitable polymer materials for the fibers 56 include,
and are not limited to, polyurethane, polycarbonate, polyether,
polyester, polyisobutylene (PIB) polyurethane, polyamide, nylon 6,
nylon 12, and polyetherimide. In some embodiments, the fibers 56 of
the fibrous matrix 50 are formed from a
poly(styrene-isobutylene-styrene) (SIBS) tri-block polymer.
[0053] The hydrogel 52 is located in between the fibers 56, i.e.
within the pores 54, of the fibrous matrix 50. In some embodiments,
the hydrogel 52 is disposed within the pores 54 of the fibrous
matrix 50 such that at least a portion of the surfaces of
individual fibers 56 within the matrix 50 are covered by the
hydrogel 52. In certain embodiments, the hydrogel 52 may be
disposed within the pores 54 to cover a substantial portion or a
majority portion of the fibers 56 within the matrix 50. In other
embodiments, the hydrogel 52 may be disposed within the pores 54 to
cover only a minority portion of the fibers 56 within the matrix
50. In some embodiments, the hydrogel 52 may be disposed within at
least a portion of the pores 54 of the matrix 50.
[0054] In some embodiments, when the hydrogel 52 is disposed within
the pores 54, the hydrogel 52 may either completely fill or
partially fill the pores 54 of the fibrous matrix 50. For example,
the hydrogel 52 may fill at least one-third of the total volume of
the pores 54 within the fibrous matrix 50. In another example, the
hydrogel 52 may fill at least three-fourths of the total volume of
the pores 54 within the fibrous matrix 50. In some embodiments, the
hydrophilic hydrogel 52 may interpenetrate the pores 54 of the
fibrous matrix 50 and create an interconnected hydrogel network
throughout the interior of the fibrous matrix 50. In some
embodiments, the hydrogel network may extend from a first surface
42 of the cross-linked hydrophilic polymer coating 40 to a second
and opposite surface 44 of the polymer coating 40 by
interpenetrating, filling, or being disposed within the pores of
the matrix 50. The hydrogel 52 serves to increase the
hydrophilicity of the fibrous matrix 50, which in turn, may provide
the lead 10 with increased sensing and pacing properties.
[0055] Suitable materials for the hydrogel 52 include materials
that increase the hydrophilicity of the cross-linked hydrophilic
polymer coating 40 as compared to the fibrous matrix 50. In some
embodiments, the hydrogel 52 may comprise one or more thermoset
polymers. In other embodiments, the hydrogel 52 may comprise one or
more thermoplastic polymers. In yet other embodiments, the hydrogel
may comprise a combination of thermoplastic and thermoset polymers.
In some embodiments, the hydrogel 52 comprises a polyethylene
glycol (PEG) or a PEG derivative, for example, chitosan-PEG,
thiol-PEG, maleimide-PEG, amino-PEG, azide-PEG, and carboxyl-PEG.
Examples of other hydrophilic materials include, but are not
limited to, poly [N-(2-hydroxypropyl)methacrylamide] (PHPMA),
poly(vinyl pyrrolidone), polyethylene/oligoethylene, polyHEMA,
polytetraglyme, hyalorunic acid, chitosan, and any derivatives
thereof.
[0056] The average number molecular weight of the hydrogel polymer
constituent may affect the physical integrity of the cross-linked
hydrophilic polymer coating 40. For example, a hydrogel 52
comprising a low number molecular weight PEG may yield a more
ductile polymer coating 40 than one that uses a hydrogel 52
comprising a high number molecular weight PEG. In some embodiments,
a hydrogel 52 comprises a polymer having a low number molecular
weight. For example, a low number molecular weight (M.sub.N) PEG
may have a number molecular weight range from about 400 g/mol to
5,000 g/mol. In other embodiments, a hydrogel 52 comprises a
polymer having a high number molecular weight. For example, a high
number molecular weight PEG may have a number molecular weight
range from about 5,000 g/mol to 30,000 g/mol. In some examples, a
suitable number molecular weight for PEG may range from about 550
g/mol to 1000 g/mol.
[0057] In some embodiments, the hydrogel 52 may be produced by
cross-linking a hydrogel solution that also includes a curing
initiator. Cross-linking may be achieved using a wide variety of
free radical initiators, such as a thermal initiator or a
photoinitiator. A thermal initiator is a chemical compound that
decomposes and produces free radicals when subjected to heat. A
photointiator is a chemical compound that produces free radicals
when exposed to UV light. The curing initiator may be added to the
hydrogel solution prior to the hydrogel 52 being applied to the
fibrous matrix 50.
[0058] In some embodiments, peroxide may be used as the free
radical initiator. Peroxide free radical initiators are thermal
initiators that may be prepared from alcohols, ketones, and acids.
Such peroxides may also be further stabilized or derivativized
through the formation of ethers, acetals, and esters. Examples of
commonly commercially available peroxides include, but are not
limited to, benzoyl peroxide, 2-butanone peroxide,
t-butylperacetate, t-butylperoxide,
2,5-di(t-butylperoxy)-2,5-dimethyl-3-hexyne, dicumyl peroxide,
2,4-pentanedione peroxide, 1,1-bis(tert-butyl peroxy)cyclohexane,
lauroyl peroxide, t-butylperoxy 2-ethylhexyl carbonate.
[0059] In other embodiments, an azo initiator may be used as the
free radical initiator to cross-link hydrophilic hydrogels 52. Azo
initiators are thermal initiators derived from diasene and have the
functional group R--N+N--R', where R and R' are either an aryl or
alkyl group. Examples of azo free radical initiators include, but
are not limited to, 2,2'-azo-bisisobutyronitrile (AIBN),
1,1'-azobis(cyclohaxanecarbonitrile), and 4,4-azobis(4-cyanovaleric
acid).
[0060] In some embodiments, a photoinitiator may be used as the
free radical initiator. Examples of free radical photoinitiators
include, but are not limited to,
4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone (such as
Irgacure.RTM. 2959, available from BASF), benzil, benzoin,
benzophenone, 2,2-dimethoxy-2-phenylacetophenone,
acetophenone-based derivatives, and benzyl-based derivatives.
[0061] The hydrophilicity characteristics of the hydrogel 52, the
fibrous matrix 50, and/or the cross-linked hydrophilic polymer
coating 40 may be determined using a wettability test, for example,
the AATCC Test Method 39-1977 promulgated by the American
Association of Textile Chemists and Colorists for the evaluation of
wettability of fabric. Hydrophilicity characteristics may also be
assessed using, for example, the ASTM Test Method D5725-99
promulgated by the American Society for Testing and Materials,
which assesses the surface wettability and absorbency of sheeted
materials using an automated contact angle tester. Typically, the
wettability test records the average time of a liquid droplet to
visibly wet, or to be absorbed by, a tested material.
[0062] The hydrophilicity (or wettability) characteristics of a
material may also be determined using a contact angle test. Contact
angle test measurements assess the wettability characteristics of a
material by observing the spreading of a given liquid over a given
surface. For example, a bead of liquid will form absent complete
wetting. In the contact angle test, a liquid droplet is placed on a
solid surface and is surrounded by a gas. The contact angle
(.theta..sub.c) is the angle formed by the liquid droplet at the
three phase boundary, or a liquid, gas, and solid intersection
point. A liquid droplet on a hydrophobic surface will exhibit a
high contact angle (see FIG. 4) while a liquid droplet on a
hydrophilic surface will exhibit a smaller contact angle (see FIG.
5), or no contact angle if the droplet has been completely absorbed
into the solid surface. Generally, the contact angle for a
hydrophobic surface is less than 90 degrees while the contact angle
for a hydrophilic surface is greater than 90 degrees.
[0063] Hydrogels 52 may be applied to the fibrous matrix 50 to
create a cross-linked hydrophilic polymer coating 40 that is more
hydrophilic than the fibrous matrix 50. The hydrophilicity of a
material composed of a fibrous matrix 50 may therefore be enhanced
by disposing the hydrogel 52 within the pores 54 of the fibrous
matrix 50. In some embodiments, the hydrogel 52 is disposed within
the pores 54 of a fibrous matrix 50 having fibers 56 that exhibit a
lower hydrophilicity than the hydrogel 52. For example, a PEG
hydrogel 52 may be disposed within the pores 54 of a SIBS fibrous
matrix 50 to produce a polymer coating 40 that is more hydrophilic
than the matrix 50 because the PEG hydrogel 52 is a more
hydrophilic material than the SIBS material. In other embodiments,
the hydrogel 52 is disposed within the pores 54 of a fibrous matrix
50 having fibers 56 that exhibit hydrophobicity.
I. Method of Creating a Cross-Linked Hydrophilic Coating
[0064] The cross-linked hydrophilic polymer coating 40 may be
constructed using various methods and processes. Non-limiting
examples of various methods and processes are provided
hereinafter.
[0065] The fibrous matrix 50 may be constructed using various
processes, for example, electrospinning and/or melt blowing. The
processes discussed herein or other similar processes may be used
to construct a fibrous matrix 50. In certain embodiments, the fiber
matrix 50 may be formed partially or completely with fibers 56
using modified electrospinning and melt-blowing techniques. Methods
for forming the fibrous matrix 50 are generally described in U.S.
application Ser. No. 13/571,553, filed Aug. 10, 2012, entitled
METHOD FOR COATING DEVICES USING ELECTROSPINNING AND MELT BLOWING,
which is incorporated herein by reference in its entirety.
[0066] In melt-blowing, an apparatus is configured to accommodate a
polymer melt. The polymer melt passes through an orifice and is
carried through the orifice via streams of hot air that pass
through the apparatus. As the polymer melt exits the orifice, it is
met with streams of heated air that helps elongate the polymer
melt. As a result, the polymer melt forms fibers 56 that impinge
onto a collector. An element to be coated, such as a substrate, may
simply be placed on or in front of the collector.
[0067] In electrospinning, an electric field may be used to draw a
polymer solution or melt from a capillary source. In some
embodiments, the capillary source may be a syringe. The polymer
solution or melt is drawn to a grounded collector. A high voltage
power supply may be used to power the process. The element to be
coated, such as a substrate, may be placed on the collector to be
coated. Upon drying, the electrospun material may form a thin
polymeric web. In some embodiments, the fiber sizes may be
controlled by adjusting the relative concentration of polymer in
the polymer solution or melt.
[0068] The fibrous matrix 50 may undergo surface processing prior
to a hydrogel coating application. In some embodiments, the surface
processing may change the surface characteristic of the fibrous
matrix 50 to facilitate the hydrogel coating application process.
In certain embodiments, surface processing may clean the surface,
activate the surface, neutralize surface static, and/or realign
fiber orientation in the fibrous matrix 50. One example of surface
processing includes, but is not limited to, plasma treating.
[0069] Plasma treating is a surface modification process that uses
ionized gas molecules to alter the surface characteristics of a
polymer. Plasma treatment may remove volatile organic compounds
from a polymeric material. Also, plasma treatment may be used to
activate the surface of a polymeric material that does not
typically bond easily, or exhibits hydrophobic characteristics. In
some embodiments, plasma treating may be used to temporary activate
the surface of the fibrous matrix 50 before the hydrogel 52 is
applied.
[0070] The hydrogel 52 may be incorporated into the fibrous matrix
50 by producing a hydrogel solution and applying the hydrogel
solution onto the matrix 50. For example, PEG may be dissolved in
isopropyl alcohol (IPA) to produce a 1.5 wt % to 5 wt % solution.
In some embodiments, a centrifugal force mixer, or other similar
equipment, may be used to mix the solution.
[0071] The hydrogel solution may also include a curing initiator.
The curing initiator is a free radical initiator that may be
activated later in the process to cross-link the hydrophilic
hydrogel 52. The curing initiator may be activated after the
hydrogel 52 has been disposed within the pores 54 of the fibrous
matrix 50. Once activated, the curing initiator cross-links
individual hydrophilic hydrogel chains together.
[0072] The hydrogel solution may be applied to the fibrous matrix
50 using various application methods. Examples of possible
application methods include, but are not limited to, dip coating,
roll coating, spray coating, flow coating, electrostatic spraying,
plasma spraying, spin coating, curtain coating and silkscreen
coating.
[0073] The hydrogel 52 may be subjected to a curing process to
crosslink individual hydrogel polymer chains together. The curing
process may depend on the curing initiator. In some embodiments,
the hydrogel curing process may be initiated by heat or UV light.
In other embodiments, vacuum pressure may be used to initiate the
free radical initiator and/or to optimize the hydrogel
cross-linking process. In some embodiments, the coated fibrous
matrix 50 may be placed into an oven to initiate or accelerate the
curing of the hydrogel 52. In other embodiments, the hydrogel
curing process may be initiated by UV light. Additionally or
alternatively, the individual hydrogel polymer chains may crosslink
together when the hydrogel contacts an activated surface of the
fibrous matrix 50. For example, the surface of the fibrous matrix
50 may be activated by a plasma treatment as described herein, and
the hydrogel polymer chains may crosslink together when they
contact the activated surface.
[0074] As described previously herein, the cross-linked hydrophilic
polymer coating 40 may be formed directly on the assembled lead 10
or a component of the lead 10. Alternatively, the polymer coating
40 may be initially formed on a substrate and subsequently
transferred onto the lead 10 or a component of the lead 10.
[0075] Although the description herein discusses the cross-linked
hydrophilic polymer coating 40 on a lead 10, the cross-linked
hydrophilic polymer coating 40 may be applied to any medical
electrical device such as, but not limited to, implantable
electrical stimulation systems and cardiac systems. Examples of
implantable electrical stimulation systems include neurostimulation
systems, such as spinal cord stimulation (SCS) systems, deep brain
stimulation (DBS) systems, peripheral nerve stimulation (PNS)
systems, gastric nerve stimulation systems, cochlear implant
systems, and retinal implant systems, among others. Examples of
cardiac systems include implantable cardiac rhythm management (CRM)
systems, implantable cardioverter-defibrillators (ICD's), and
cardiac resynchronization and defibrillation (CRDT) devices, among
others.
[0076] Cross-linked hydrophilic polymer coatings 40 can provide
several benefits for medical electric leads 10 and electrodes 28.
Cross-linked hydrophilic polymer coatings 40 may be able to improve
the wettability of membranes and nanofibrous materials used in
medical lead bodies 12 and electrodes 28. As a result, the
electrical performance of the electrodes 28 and lead bodies 12 may
be significantly improved. Other benefits of the polymer coating 40
may also include providing a biostable surface and preventing cell
adhesion to the electrical leads 10 and electrodes 28. In some
cases, the cross-linked hydrophilic polymer coating 40 can be a
cost-efficient alternative to other alternative hydrophilic
structures. Because of the ability of the cross-linked hydrophilic
polymer coating 40 to conform to any geometry, the polymer coating
40 may be easily applied to custom electrode geometries. In
contrast, alternative hydrophilic structures may be limited to
extrusion and molding processes, which cannot accommodate irregular
electrode geometries.
[0077] Specific examples of a fibrous matrix 50 and a cross-linked
hydrophilic polymer coating 40 are provided herein. FIG. 6 provides
an image of a fibrous matrix 50 formed by poly(vinylidene
fluoride-co-hexafluoropropene) (PVDF-HFP) fibers 56. FIG. 7 shows
an image of a cross-linked hydrophilic polymer coating 40 formed by
a polyethylene glycol (PEG) hydrogel 52 and a poly(vinylidene
fluoride-co-hexafluoropropene) (PVDF-HFP) fibrous matrix 50. As
shown by FIG. 7, the hydrogel 52 is disposed in the spaces, i.e.
pores 54, between the fibers 56 and over the surface of the fibers
56 of the fibrous matrix 50.
EXAMPLE 1
[0078] The present invention is more particularly described in the
following example, which is intended as illustration only, since
numerous modifications and variations within the scope of the
present invention will be apparent to those skilled in the art.
Moisture Absorption Comparison Study
Control Samples
[0079] Control samples were SIBS matrixes that were constructed
using an electrospinning process. Control samples did not contain a
hydrogel.
Test Samples
[0080] Test samples were cross-linked hydrophilic polymer coating
specimens that included a SIBS matrix and a PEG 770 hydrogel. The
SIBS matrixes were constructed using an electrospinning
process.
[0081] The following process steps were used for constructing the
cross-linked hydrophilic polymer coating on the test samples.
[0082] One gram of polyethylene glycol (PEG) 770 was added to a
mixing container, and mixed with 20 mL of isopropyl alcohol (IPA)
to obtain a 5% solution of PEG 770 in IPA. The solution of PEG 770
in IPA was thoroughly mixed using a centrifugal force mixer until
the PEG 770 had completely dissolved in solution. At least 9 mg of
dibenzoyl peroxide was added to the PEG solution and mixed until
the dibenzoyl peroxide was completely dissolved in the
solution.
[0083] The SIBS fibrous matrix was placed in a plasma treatment
oven. An argon plasma treatment was applied to clean the surface of
the SIBS matrix, followed by an oxygen plasma treatment.
[0084] Once the oxygen treatment was completed, the PEG
770/dibenzoyl peroxide mixture was applied to the SIBS matrix 50 by
dropping a series of droplets of the hydrogel mixture onto one or
more surfaces of the matrix 50.
[0085] After application of the mixture, the coated test samples
were placed in a vacuum oven at room temperature and vacuum oven
was set to approximately -22 inHg.
[0086] Once the target pressure was reached, the oven temperature
was increased to 60 degrees Celsius. Samples were subjected to
these oven conditions for one hour.
Moisture Absorption Test Method
[0087] Test and control samples were each labeled accordingly and
placed on one end of a 1.83 mm (or 0.072 inch) diameter rod.
[0088] Once each sample was properly placed on a rod, the samples
were transferred onto a small faceplate (i.e. polyether ether
ketone (PEEK) faceplate).
[0089] Prior to testing, samples were subjected to a drying process
in a vacuum oven for two hours. The vacuum oven was set to a
pressure of -22 inHg and a temperature of 40 degrees Celsius during
this drying process.
[0090] Once the drying process was completed, the samples were
taken out of the vacuum oven and removed from the faceplate. A
water droplet was placed on surface of each sample and after three
minutes, each sample was observed for water droplet absorption. If
the droplet was not visible on the surface of the sample after
three minutes, the sample was recorded to have absorbed the water
droplet.
Results
TABLE-US-00001 [0091] TABLE 1 Moisture absorption data Number of
Absorbed Total Number of Droplet Observations Observations Test
Samples 8 10 Control Samples 2 10
[0092] The number of observations of an absorbed droplet in the
test group and the control group are shown in Table 1. Observations
were made three minutes after the each droplet has been placed on
the surface of each sample.
[0093] Table 1 shows that the test group had 8 out of 10
observations of an absorbed water droplet. The control group had 2
out of 10 observations of an absorbed water droplet. The results
show that a cross-linked hydrophilic polymer coating (i.e. a SIBS
fibrous matrix containing a PEG 770 hydrogel) exhibits higher
hydrophilicity than a SIBS fibrous matrix containing no
hydrogel.
* * * * *