U.S. patent application number 16/146566 was filed with the patent office on 2019-04-04 for method for producing nanosurfaces with nano, micron, and/or submicron structures on a polymer.
This patent application is currently assigned to NANOVIS, INC.. The applicant listed for this patent is NANOVIS, INC.. Invention is credited to Ganesan BALASUNDARAM, Matthew HEDRICK, Chang YAO.
Application Number | 20190099519 16/146566 |
Document ID | / |
Family ID | 45372086 |
Filed Date | 2019-04-04 |
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United States Patent
Application |
20190099519 |
Kind Code |
A1 |
HEDRICK; Matthew ; et
al. |
April 4, 2019 |
METHOD FOR PRODUCING NANOSURFACES WITH NANO, MICRON, AND/OR
SUBMICRON STRUCTURES ON A POLYMER
Abstract
The present invention relates to a modified polymeric material.
The modified polymeric material includes a polymer having a
modified surface, where the modified surface includes nano, micron,
and/or submicron scale features. The present invention also relates
to an implant comprising the modified polymeric material. The
present invention further relates to processes for making the
modified polymeric material and the implant.
Inventors: |
HEDRICK; Matthew; (Carmel,
IN) ; BALASUNDARAM; Ganesan; (Minneapolis, MN)
; YAO; Chang; (West Lafayette, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NANOVIS, INC. |
Columbia City |
IN |
US |
|
|
Assignee: |
NANOVIS, INC.
West Lafayette
IN
|
Family ID: |
45372086 |
Appl. No.: |
16/146566 |
Filed: |
September 28, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15066747 |
Mar 10, 2016 |
10117966 |
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16146566 |
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13704735 |
Jul 25, 2013 |
9393092 |
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PCT/US2011/041490 |
Jun 22, 2011 |
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15066747 |
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61358851 |
Jun 25, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 31/048 20130101;
A61L 31/06 20130101; A61L 31/14 20130101; B29C 59/022 20130101;
B29K 2071/00 20130101; A61L 2400/18 20130101; Y10T 428/2978
20150115; C08L 71/00 20130101; A61B 17/0401 20130101; A61L 17/14
20130101; A61L 17/04 20130101; A61L 31/06 20130101; C08L 23/10
20130101; Y10T 428/24355 20150115; A61F 2/0063 20130101; C08F
110/06 20130101; A61L 27/50 20130101; B29L 2031/7532 20130101; A61L
27/10 20130101; A61L 27/18 20130101; A61B 17/06166 20130101; A61L
31/048 20130101; A61C 8/00 20130101; A61L 27/18 20130101; C08G
65/4012 20130101; C08G 65/46 20130101; Y10T 428/2982 20150115; C08L
23/10 20130101; C08L 71/00 20130101; C08L 23/10 20130101; C08L
71/00 20130101; C08G 2650/40 20130101; C08G 63/88 20130101; B29C
41/24 20130101; A61L 17/04 20130101; A61L 2400/12 20130101 |
International
Class: |
A61L 27/18 20060101
A61L027/18; A61L 31/06 20060101 A61L031/06; C08L 71/00 20060101
C08L071/00; C08L 23/10 20060101 C08L023/10; A61L 17/04 20060101
A61L017/04; A61L 17/14 20060101 A61L017/14; A61L 27/50 20060101
A61L027/50; A61L 31/04 20060101 A61L031/04; C08F 110/06 20060101
C08F110/06; C08G 65/40 20060101 C08G065/40; A61L 31/14 20060101
A61L031/14; C08G 63/88 20060101 C08G063/88; A61B 17/04 20060101
A61B017/04; A61B 17/06 20060101 A61B017/06; A61C 8/00 20060101
A61C008/00; A61F 2/00 20060101 A61F002/00; B29C 59/02 20060101
B29C059/02; C08G 65/46 20060101 C08G065/46; A61L 27/10 20060101
A61L027/10 |
Claims
1. A modified polymeric material comprising a polymer having a
modified surface, wherein said modified surface comprises nano,
micron, and/or submicron scale features.
2. The modified polymeric material according to claim 1, wherein
the polymer is a thermoplastic polymer.
3. The modified polymeric material according to claim 2, wherein
the thermoplastic polymer is selected from the group consisting of
polypropylene, polyetheretherketone (PEEK), poly lactic glycolic
acid, poly lactic lactic acid, poly lactic acid, polyurethane, and
the like.
4. The modified polymeric material according to claim 1, wherein
the polymer is in the form of a polymeric film, fiber, sphere,
ovoid, rod, filament, monofilament, or scaffold, plug, or
matrix.
5. The modified polymeric material according to claim 1, wherein
said modified polymeric material is effective to modify biological
response (e.g., increased or decreased tissue or bacteria
attachment), fixation (e.g., improve mechanical interface with
bone), or therapeutic attachment/delivery compared to a
corresponding non-modified polymeric material.
6. The modified polymeric material according to claim 5, wherein
the biological response is selected from the group consisting of
protein or antibody adsorption, cell attachment, cell function, and
tissue growth.
7. The modified polymeric material according to claim 5, wherein
the therapeutic is selected from the group consisting of a peptide,
protein, growth factor, antibody, drug, metal, antimicrobial metal,
biologic tissue, biologic agent, chemical agent, stem cell,
modified cell, and the like.
8. The modified polymeric material according to claim 1 further
comprising: a functional attachment effective to increase
biological response or therapeutic attachment/delivery; and/or a
ceramic, metal, or another polymer integrated into the modified
polymeric material or coated onto the surface of the modified
polymeric material.
9. The modified polymeric material according to claim 8, wherein
the functional attachment is selected from the group consisting of
a peptide, protein, growth factor, antibody, drug, metal,
antimicrobial metal, biologic tissue, biologic agent, chemical
agent, stem cell, modified cell, and the like.
10. An implant comprising: a modified polymeric material according
to claim 1.
11. The implant according to claim 10, wherein the polymer is
polypropylene and the implant is a hernia mesh or polymer
suture.
12. The implant according to claim 10, wherein the polymer is PEEK
and the implant is a spine cage, vertebral body replacement, suture
anchor, dental implant, maxillofacial implant, or the like.
13. A process for preparing a modified polymeric material, said
process comprising: providing a polymer; and subjecting the polymer
to a high vacuum treatment regimen under conditions effective to
modify the surface of the polymer by introducing nano, micron,
and/or submicron scale features to the surface of the polymer.
14. The process according to claim 13, wherein the high vacuum
treatment regimen comprises: heating the polymer at a high
temperature; and/or incubating the heat-treated polymer in a vacuum
chamber under high vacuum conditions effective to modify the
surface of the polymer, wherein said heating can be at a heat range
specific to the polymer and relative to the polymer's melting and
crystallization temperature.
15. The process according to claim 14, wherein said heating is
carried out at a temperature of between about 300.degree. C. and
about 400.degree. C.
16. The process according to claim 14, wherein said heating is
carried out at a temperature of about 350.degree. C. for between
about 1 and about 90 minutes.
17. The process according to claim 13, wherein said incubating is
carried out for at least 5 hours.
18. The process according to claim 13, wherein the high vacuum
treatment regimen comprises: subjecting the polymer to heating and
simultaneous high vacuum conditions effective to modify the surface
of the polymer.
19. The process according to claim 18, wherein said subjecting
comprises: (a) loading the polymer at a temperature of about
150.degree. C.; (b) applying high vacuum conditions of about 10
mTorr; (c) increasing the temperature to about 350.degree. C. over
the course of about 1 hour; (d) maintaining the polymer at about
350.degree. C. at 10 mTorr for about 1 hour; (e) decreasing the
temperature to about 150.degree. C. over the course of about 1
hour; and (f) extracting the polymer at about 150.degree. C.
20. The process according to claim 19 further comprising: storing
the extracted polymer under high vacuum conditions for about 8
hours.
21. A process for preparing a modified polymeric material, said
process comprising: providing a polymer; and incubating the polymer
in mild heat in a vacuum chamber under high vacuum conditions
effective to modify the surface of the polymer by introducing nano,
micron, and/or submicron scale features to the surface of the
polymer.
22. The process according to claim 21, wherein said mild heat
comprises a temperature of not more than 70.degree. C.
23. The process according to claim 21, wherein said incubating is
carried out for between about 18 and 30 hours.
24. A process for preparing a modified polymeric material, said
process comprising: providing a polymer; and incubating the polymer
in methylene chloride in a vacuum chamber under high vacuum
conditions effective to modify the surface of the polymer by
introducing micron and/or submicron scale features to the surface
of the polymer.
25. The process according to claim 24, wherein said incubating is
carried out for between about 18 and 30 hours.
26. The process according to claim 13 further comprising: applying
an acid etching procedure either before or after the polymer is
modified; and/or integrating/coating the modified polymeric
material with hydroxyapatite, titanium, calcium phosphate, and/or
the like to yield a two layer or integration of the modified
polymeric material and the hydroxyapatite, titanium, calcium
phosphate, and the like.
27. The process according to claim 13, wherein the polymer is a
thermoplastic polymer.
28. The process according to claim 27, wherein the thermoplastic
polymer is selected from the group consisting of polypropylene,
polyetheretherketone (PEEK), poly lactic glycolic acid, poly lactic
lactic acid, poly lactic acid, polyurethane, and the like.
29. The process according to claim 13, wherein the polymer is in
the form of a polymeric film, fiber, sphere, ovoid, rod, filament,
monofilament, or scaffold, plug, or matrix.
30. The process according to claim 13, wherein said modified
polymeric material is effective to modify biological response
(e.g., increased or decreased tissue or bacteria attachment),
fixation (e.g., improve mechanical interface with bone), or
therapeutic attachment/delivery compared to a corresponding
non-modified polymeric material.
31. The process according to claim 30, wherein the biological
response is selected from the group consisting of protein or
antibody adsorption, cell attachment, cell function, and tissue
growth.
32. The process according to claim 30, wherein the therapeutic is
selected from the group consisting of a peptide, protein, growth
factor, antibody, drug, metal, antimicrobial metal, biologic
tissue, biologic agent, chemical agent, stem cell, modified cell,
and the like.
33. The process according to claim 13 further comprising: a
functional attachment effective to increase biological response or
therapeutic attachment/delivery; and/or a ceramic, metal, or
another polymer integrated into the modified polymeric material or
coated onto the surface of the modified polymeric material.
34. The process according to claim 33, wherein the functional
attachment is selected from the group consisting of a peptide,
protein, growth factor, antibody, drug, metal, antimicrobial metal,
biologic tissue, biologic agent, chemical agent, stem cell,
modified cell, and the like.
35. A modified polymeric material produced by the process according
to claim 13.
36. A modified polymeric material according to claim 35, wherein
said modified polymeric material can be used as, used with, or
combined with biomaterials (e.g., scaffolds, bone void fillers,
fusion materials autograft, Demineralized bone graft, allograft,
xenograft, and the like), components, local and systemic drug
delivery materials/polymers, and various other items suitable for
being used or combined with the modified polymeric material.
37. A modified polymeric material according to claim 35, wherein
said modified polymeric material further includes two
layer/integration aspects (e.g., integrating/coating with
hydroxyapatite, titanium, calcium phosphate).
38. An implant comprising a modified polymeric material produced
according to the process of claim 13.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application of U.S.
application Ser. No. 15/066,747, filed with the U.S. Patent and
Trademark Office of Mar. 10, 2016, which is a continuation
application of U.S. application Ser. No. 13/704,735, filed with the
U.S. Patent and Trademark Office on Jul. 25, 2013, which is a
national stage filing under section 371 of International
Application No. PCT/US2011/041490, filed on Jun. 22, 2011, and
published in English on Dec. 29, 2011 as WO 2011/163393, which
claims the benefit of U.S. Provisional Patent Application Ser. No.
61/358,851, filed Jun. 25, 2010. The entire disclosures of each of
the prior applications are hereby incorporated by reference
herein.
FIELD OF THE INVENTION
[0002] The present invention relates to a modified polymeric
material. The present invention also relates to an implant
comprising the modified polymeric material. The present invention
further relates to processes for making and using the modified
polymeric material and the implant.
BACKGROUND OF THE INVENTION
[0003] There is an interest in the potential use of synthetic
polymers and the effect they may have on the design and function of
hard and soft tissue repair. To that end, various
nanotechnology-based approaches have been taken.
[0004] However, current methods for creating a surface roughness
(e.g., at the submicron and micron level) are deficient in terms of
scaling, cost, complexity, reagent acquisition, disposal, and
accessibility, biocompatibility, and mechanical properties of the
substrate.
[0005] Other deficiencies in the art of producing synthetic
polymers having rough surfaces at the nano, submicron, and micron
level include, for example, the following: (i) current methods to
create nanosurface roughness on polymers are difficult in
maintaining consistency across the material type; (ii) current
methods to create nanosurface roughness on polymers use chemicals
that are potentially toxic if such chemicals are not completely
removed; (iii) current methods to create nanosurface roughness on
polymers use coating methods that can result in delamination of the
polymer or added material and wear debris formation; (iv) current
methods to create nanosurface roughness on polymers are difficult
to apply in three dimensions/outside of direct line of site; and
(v) current methods have difficulty creating both porous voids and
aspirities.
[0006] The present invention is directed to overcoming these and
other deficiencies in the art.
SUMMARY OF THE INVENTION
[0007] In one aspect, the present invention relates to a modified
polymeric material, as described herein. In one embodiment, the
modified polymeric material of the present invention includes a
polymer having a modified surface, where the modified surface
includes nano, micron, and/or submicron scale features, including,
but not limited to, pores, peaks, valleys, and ridges.
[0008] In another aspect, the present invention relates to an
implant that includes a modified polymeric material, as described
herein.
[0009] In a further aspect, the present invention relates to a
process for preparing a modified polymeric material, as described
herein.
[0010] In one embodiment, the process involves providing a polymer,
and subjecting the polymer to a high vacuum treatment regimen under
conditions effective to modify the surface of the polymer by
introducing nano, micron, and/or submicron scale features to the
surface of the polymer. The high vacuum treatment regimen can
include heating the polymer at a high temperature, and then
incubating the heat-treated polymer in a vacuum chamber under high
vacuum conditions effective to modify the surface of the
polymer.
[0011] In another embodiment, the process involves providing a
polymer, and incubating the polymer in mild heat in a vacuum
chamber under high vacuum conditions effective to modify the
surface of the polymer by introducing nano, micron, and/or
submicron scale features to the surface of the polymer.
[0012] In yet another embodiment, the process involves providing a
polymer, treating the polymer with a chemical, enzyme, or other
agent to soften the surface, and then subjecting the polymer to
vacuum conditions effective to modify the surface of the polymer by
introducing nano, micron, and/or submicron scale features to the
surface of the polymer.
[0013] In yet another embodiment, the process involves providing a
polymer, and incubating the polymer in methylene chloride, or other
chemical, pharmaceutical, biologic agent, antibiotics,
antimicrobial or bacterial static metals or other agents, growth
factors, peptides, antibodies, viruses, RNAi, ceramic including but
not limited to hydroxyapatite and calcium phosphate in all size
ranges, metal including but not limited to titanium, Ti6Al4V, or
another polymer in a vacuum chamber under high vacuum conditions
effective to modify the surface of the polymer by introducing nano,
micron, and/or submicron scale features to the surface of the
polymer and coat or integrate the chemical, pharmaceutical,
antibiotic, antimicrobial or bacterio-static metal or other agent,
biologic agent, growth factors, peptides, antibodies, virus, RNAi,
ceramic, metal or another polymer to the polymer.
[0014] Alternatively, the polymer could have the above agents in
the polymer prior to the process.
[0015] In another aspect, the present invention relates to a
modified polymeric material produced according to the processes
described herein, as well as to implants containing the modified
polymeric material.
[0016] The present invention provides a robust method for producing
nanosurfaces and nanosurfaces with nano, submicron, and micron
scale features on polymers, including nanosurfaced
polyetheretherketone (PEEK) spine cages and nanosurfaced
polypropylene hernia meshes, polymer sutures and various polymers,
including those used for implants, biomaterials, or drug delivery
materials in any type of human or animal tissue.
[0017] The modified polymeric material of the present invention can
be used for both hard and soft tissue repair. In one aspect, the
invention is effective in developing nano-PEEK spine cages to treat
spine repair and other applications that use PEEK polymer.
Additionally, the invention provides nanosurfaced polypropylene
hernia meshes. The invention further provides an inexpensive and
consistent process that creates a nanosurface on polymers with a 2
or 3 dimensional geometry. The process of the present invention is
useful in that it is easily scalable, does not use chemicals, and
preserves the biocompatibility and mechanical properties of the
substrate material. Furthermore the nanosurface of the modified
polymeric material of the present invention can be useful in
improving or modifying biological responses, including protein or
antibody adsorption, cell attachment, cell function, and subsequent
tissue growth. The surface of the modified polymeric material of
the present invention can also improve therapeutic attachment and
delivery of various attachments, including, for example, peptides,
proteins, antibodies, drugs, metals, antimicrobial metals, biologic
tissues or agents, stem cells, modified cells, and the like.
[0018] The present invention also provides PEEK and polypropylene
surfaces that mimic natural tissues, and that may be more bioactive
and, thus, provide improved hard and soft tissue integration
markers compared to conventional PEEK and polypropylene surfaces.
As mentioned, the present invention provides a nano to nano and
micron rough surface.
[0019] With regard to biomedical uses, currently existing
conventional PEEK materials to treat spine repair possess smooth
material surface features. The same trend applies to polypropylene
based materials that are widely used in hernia repair applications.
Therefore, nano rough surface modification of such polymeric
materials, as provided by the present invention, is a new paradigm
for quick repair and surrounding tissue integration.
[0020] The present invention provides, in one aspect, a process for
preparing a modified polymeric material using simultaneous heat and
vacuum treatment on PEEK polymeric material (without chemical
process) to create nano rough surface without compromising the
mechanical, physical and chemical property of the polymer.
[0021] For polypropylene hernia meshes, the present invention
provides, in one aspect, a method that uses a high vacuum source in
the presence of pre-set mild heat or highly volatile methylene
chloride treatment. The methylene chloride has a very low boiling
point (less than 40.degree. C.; close to body temperature heat) and
can be removed spontaneously during the high vacuum treatment.
[0022] The present invention also relates to incorporating the
process for preparing a modified polymeric material into the PEEK
manufacturing process. This modified process can be useful for
creating a surface or pores in polymers (such as when the polymer
is molded/extruded for the first time).
[0023] The present invention also relates to using the process for
preparing a modified polymeric material to surfaces that are
already modified or will be modified thereafter. For example, the
present invention contemplates using the modified process of the
present invention to the top of a previously modified surface, and
also contemplates using another method (e.g., acid etching) to
further modify the modified surface after the process for preparing
the modified polymeric material to the surface is completed.
[0024] These and other objects, features, and advantages of this
invention will become apparent from the following detailed
description of the various aspects of the invention taken in
conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] For the purpose of illustrating aspects of the present
invention, there are depicted in the drawings certain embodiments
of the invention. However, the invention is not limited to the
precise arrangements and instrumentalities of the embodiments
depicted in the drawings. Further, as provided, like reference
numerals contained in the drawings are meant to identify similar or
identical elements.
[0026] FIG. 1 is a schematic of one embodiment of the process of
the present invention for preparing a modified polymeric material.
In this embodiment, the process produces a nano PEEK modified
polymeric material.
[0027] FIG. 2 are SEM images of the surface of PEEK (plain) and of
the surface of modified nano PEEK after treatment using one
embodiment of the process of the present invention.
[0028] FIG. 3 are high magnification SEM images of the surface of
PEEK (plain) and of the surface of a modified nano PEEK of the
present invention.
[0029] FIG. 4 is an EDS spectra of nano and conventional PEEK.
[0030] FIG. 5 is a bar graph showing heat-plus-vacuum treated PEEK
calcium deposition data with osteoblast cells.
[0031] FIG. 6 are schematics of one embodiment of the process of
preparing a surface modified nanopolypropylene of the present
invention.
[0032] FIGS. 7A-7C are SEM images of a polypropylene mesh (plain)
(FIG. 7A) and of polyproplyene meshes of the present invention
having various nano features. FIG. 7B shows an SEM image of the
surface a nanopolypropylene mesh produced using methylene chloride
treatment with high vacuum. FIGS. 7C shows an SEM image of the
surface a nanopolypropylene mesh produced using pre-set heat with
high vacuum.
[0033] FIG. 8 is a bar graph showing calcium deposition data with
osteoblast cells for PEEK (untreated), nanoPEEK 1 (H.sub.2SO.sub.4
treated), and nanoPEEK 2 (heated at 350.degree. C. for 1 hour
followed by vacuum) after 1 week, 2 weeks, and 3 weeks.
[0034] FIGS. 9A-9B are SEM images of the surface of modified nano
PEEK materials produced according to one embodiment of the process
of preparing a modified polymeric material of the present
invention.
[0035] FIGS. 10A-10B are SEM images of the surface of modified nano
PEEK materials produced according to one embodiment of the process
of preparing a modified polymeric material of the present
invention.
[0036] FIGS. 11A-11B are SEM images of the surface of modified nano
PEEK materials produced according to one embodiment of the process
of preparing a modified polymeric material of the present
invention.
[0037] FIG. 12 is an SEM image of the surface of a modified nano
PEEK material produced according to one embodiment of the process
of preparing a modified polymeric material of the present
invention.
[0038] FIGS. 13A-13B are SEM images of the surface of non-modified
PEEK materials.
[0039] FIG. 14 is an SEM image of the surface of a non-modified
PEEK material.
[0040] FIGS. 15A-15B are SEM images of the surface of a modified
PEEK material produced using an embodiment of the process of the
present invention involving heating at 275.degree. C. using a
ramping protocol. Arrows indicate the resemblance of the features
(patterns) that were observed with 350.degree. C. condition.
DETAILED DESCRIPTION OF THE INVENTION
[0041] The present invention relates to a modified polymeric
material, as described herein. In one embodiment, the modified
polymeric material of the present invention includes a polymer
having a modified surface, where the modified surface includes
nano, micron, and/or submicron scale features. In one embodiment,
the nano, micron, and/or submicron scale features can include,
without limitation, surface features such as pores, peaks, valleys,
and ridges.
[0042] A suitable polymer can include, without limitation, a
thermoplastic polymer. Examples of such thermoplastic polymers
include polypropylene, polyetheretherketone (PEEK), poly lactic
glycolic acid, poly lactic lactic acid, poly lactic acid,
polyurethane, and the like. In one embodiment, the polymer is in
the form of a polymeric film. In other embodiments, the polymer is
in the form of a fiber, sphere, ovoid, rod, filament, monofilament,
scaffold, plug, matrix, or the like.
[0043] The modified polymeric material of the present invention can
be effective to modify biological response (e.g., increased or
decreased tissue or bacteria attachment), fixation (e.g., improve
mechanical interface with bone), or therapeutic attachment/delivery
compared to a corresponding non-modified polymeric material.
[0044] The modified polymeric material of the present invention can
be effective to increase biological response or therapeutic
attachment/delivery compared to a corresponding non-modified
polymeric material. Examples of biological responses contemplated
by the present invention include, without limitation, protein or
antibody adsorption, cell attachment, cell function, tissue growth,
and the like. Examples of therapeutics contemplated by the present
invention include, without limitation, peptides, proteins, growth
factors, antibodies, drugs, metals, antimicrobial metals, biologic
tissues, biologic agents, stem cells, modified cells, and the like,
including various others materials such as, but not limited to,
various ceramics (e.g., HA, CP, etc.) and metals (e.g., Ti,
etc.).
[0045] The present invention further includes treating the modified
polymeric material with a plasma treatment in an atmosphere
including, but not limited to, an oxygen atmosphere, plasma
etching, oxygenation, or plasma spraying with a ceramic, adding
allograft, Demineralized bone matrix, or xenograft.
[0046] Therefore, in one embodiment, the modified polymeric
material of the present invention can further include a functional
attachment effective to increase biological response or therapeutic
attachment/delivery. The functional attachment can include, without
limitation, a peptide, protein, growth factor, antibody, drug,
metal, antimicrobial metal, biologic tissue, biologic agent,
chemical agent, stem cell, modified cell, and the like.
[0047] In a further embodiment, the modified polymeric material of
the present invention can further include: (i) a functional
attachment effective to increase biological response or therapeutic
attachment/delivery; and/or (ii) a ceramic, metal, or another
polymer integrated into the modified polymeric material or coated
onto the surface of the modified polymeric material.
[0048] The present invention also relates to an implant that
includes a modified polymeric material, as described herein. In one
embodiment, the thermoplastic polymer is polypropylene and the
implant is a hernia mesh or polymer suture. In another embodiment,
the thermoplastic polymer is PEEK and the implant is a spine cage,
vertebral body replacement, suture anchor, dental implant, or
maxillofacial implant, and the like.
[0049] The present invention further relates to a process for
preparing a modified polymeric material, as described herein.
[0050] In one embodiment, the process involves: (i) providing a
polymer; and (ii) subjecting the polymer to a high vacuum treatment
regimen under conditions effective to modify the surface of the
polymer by introducing nano, micron, and/or submicron scale
features to the surface of the polymer. In a particular embodiment
of this process, the high vacuum treatment regimen can include: (i)
heating the polymer at a high temperature; and (ii) incubating the
heat-treated polymer in a vacuum chamber under high vacuum
conditions effective to modify the surface of the polymer. The
polymer used in this embodiment of the process of the present
invention can include, without limitation, PEEK.
[0051] The heating can be at a heat range specific to the polymer
and relative to the polymer's melting and crystallization
temperature. The incubating can be carried out for at least 5
hours.
[0052] In illustrative examples, the heating can be carried out at
a temperature of greater than 400.degree. C., between about
275.degree. C. and about 400.degree. C., between about 300.degree.
C. and about 400.degree. C., between about 325.degree. C. and about
400.degree. C., between about 350.degree. C. and about 400.degree.
C., or between about 375.degree. C. and about 400.degree. C. In a
particular embodiment, the heating can be carried out at a
temperature of about 350.degree. C. for between about 1 and about
90 minutes. The material can be heated and vacuum treated
simultaneously. The heating and simultaneous high vacuum conditions
are such as to be effective to modify the surface of the polymer in
accordance with the present invention. The temperature and vaccum
pressure can be modified to create different surface features to
achieve the desired biological response or other response or
benefit.
[0053] In a variation of this embodiment, the high vacuum treatment
regimen can include loading polymer samples at 150.degree. C. and
subjecting the polymer to pump-down procedures to 10 mTorr
(pump/purge sequences). Thereafter, the polymer is subjected to a
ramp-up period during which the temperature is increased from about
150.degree. C. to about 350.degree. C. over the course of
approximately 1 hour. The polymer is left at steady state for about
1 hour (at 10 mTorr at 350.degree. C.). The polymer is then
subjected to a ramp-down period during which the temperature is
decreased to about 150.degree. C. over the course of 1 hour. The
sample is then extracted at 150.degree. C. and transferred to a
vacuum desiccator and stored under high vacuum for approximately 8
hours.
[0054] In another embodiment, the process involves heating at
275.degree. C. using a ramping protocol, same as for 350.degree. C.
Other conditions of the process can be the same, but the maximum
temperature can be held at 275.degree. C. for 1 hour. Surface
features of a modified polymeric material produced using such
process are shown in FIGS. 15A-15B. For example, as shown in FIGS.
15A-15B, the SEM results provided a new type of surface feature in
this condition. In particular, the topography is rougher but with
less porous structure compared to 350.degree. C. treatment
condition. Again the topographical features were homogenous
throughout the surface like the 350.degree. C. treatment.
[0055] In one aspect, the process of the present invention is
effective to produce a modified polymeric material that includes a
polymer having a modified surface, where the modified surface
includes micron and/or submicron scale features. In one embodiment,
the polymer is a thermoplastic polymer, where the thermoplastic
polymer includes, but is not limited to, polypropylene and
polyetheretherketone (PEEK). In a particular embodiment, the
polymer is in the form of a polymeric film. In another embodiment,
the modified polymeric material is effective to increase biological
response or therapeutic attachment/delivery compared to a
corresponding non-modified polymeric material. The biological
response can include, without limitation, protein or antibody
adsorption, cell attachment, cell function, and tissue growth. The
therapeutic can be, without limitation, a peptide, protein, growth
factor, antibody, drug, metal, antimicrobial metal, biologic
tissue, biologic agent, chemical agent, stem cell, modified cell,
and the like. Further, the modified polymeric material can further
include a functional attachment effective to increase biological
response or therapeutic attachment/delivery. Suitable functional
attachments can include, without limitation, a peptide, protein,
growth factor, antibody, drug, metal, antimicrobial metal, biologic
tissue, biologic agent, chemical agent, stem cell, modified cell,
and the like.
[0056] In one embodiment, the process of preparing a modified
polymeric material can further include: (i) applying an acid
etching procedure either before or after the polymer is modified;
and/or (ii) integrating/coating the modified polymeric material
with hydroxyapatite, titanium, calcium phosphate, and/or the like
to yield a two layer or integration of the modified polymeric
material and the hydroxyapatite, titanium, calcium phosphate, and
the like.
[0057] In another embodiment, the process involves: (i) providing a
polymer; and (ii) incubating the polymer in mild heat in a vacuum
chamber under high vacuum conditions effective to modify the
surface of the polymer by introducing micron and/or submicron scale
features to the surface of the polymer. The polymer used in this
embodiment of the process of the present invention can include,
without limitation, polypropylene. The mild heat can be, without
limitation, a temperature of not more than about 70.degree. C. The
incubating can be carried out for between about 18 and 30
hours.
[0058] In yet another embodiment, the process involves: (i)
providing a polymer; and (ii) incubating the polymer in methylene
chloride in a vacuum chamber under high vacuum conditions effective
to modify the surface of the polymer by introducing micron and/or
submicron scale features to the surface of the polymer. The polymer
used in this embodiment of the process of the present invention can
include, without limitation, polypropylene. The incubating can be
carried out for between about 18 and 30 hours.
[0059] In another aspect, the present invention relates to a
modified polymeric material produced according to the processes
described herein, as well as to implants containing the modified
polymeric material. In view of the present disclosure, one of
ordinary skill in the art would readily be able to prepare and use
implants that contain or include the modified polymeric material of
the present invention.
[0060] In another aspect, the present invention relates to using
the modified polymeric material of the present invention as or
combined with various biomaterials (e.g., scaffolds, bone void
fillers, fusion materials autograft, Demineralized bone graft,
allograft, xenograft, and the like), components, local and systemic
drug delivery materials/polymers, and various other items suitable
for being used or combined with the modified polymeric
material.
[0061] In another aspect, the present invention provides a modified
polymeric material that further includes two layer/integration
aspects (e.g., integrating/coating with hydroxyapatite, titanium,
calcium phosphate).
[0062] One advantage of the present invention is the
straight-forward creation of novel nanosurfaced polymers for spinal
repair, spinal fusion, dental implants, biomaterials, suture
anchors, and where other alternatives are not possible, including
in porous structures that are hard to reach with fluids or line of
site methods. The method of the present invention involves no
chemical treatment or cumbersome coating technologies traditionally
used in polymer surface modifications that attempt to create a nano
rough surface. The procedure of the present invention is easy and
cost effective, efficient for mass production; in particular there
will be no chemical residues and reduced particle debris. Further,
no major bulk mechanical property will be changed since the
processing temperature involves is low compared to the melting
temperature of the polymer.
[0063] As noted herein, the present invention precludes the usage
of chemical treatment, which is a concern that needs to be
addressed in the context of cytotoxicity. Also, conventionally used
coating technologies (to create nano, micron, or submicron
roughness) possibly produce delamination or wear debris, which
results in the potential for cytotoxicity. The present invention
also provides a method to create a custom nanosurface to drive
desired protein/antibody adsorption and cell responses. For
example, this could be done by changing the process parameters to
make a different nano and micron surfaces.
[0064] Provided below are further descriptions of certain aspects
and embodiments of the present invention, some descriptions of
which reiterate or further explain various aspects and embodiments
contained elsewhere herein.
[0065] In one embodiment, the process of the present invention
involves providing a polymer, and subjecting the polymer to a high
vacuum treatment regimen under conditions effective to modify the
surface of the polymer by introducing nano, micron, and/or
submicron scale features to the surface of the polymer. The high
vacuum treatment regimen can include heating the polymer at a high
temperature, and then incubating the heat-treated polymer in a
vacuum chamber under high vacuum conditions effective to modify the
surface of the polymer.
[0066] In another embodiment, the process involves providing a
polymer, and incubating the polymer in mild heat in a vacuum
chamber under high vacuum conditions effective to modify the
surface of the polymer by introducing nano, micron, and/or
submicron scale features to the surface of the polymer.
[0067] In yet another embodiment, the process involves providing a
polymer, treating the polymer with a chemical, enzyme, or other
agent to soften the surface, and then subjecting the polymer to
vacuum conditions effective to modify the surface of the polymer by
introducing nano, micron, and/or submicron scale features to the
surface of the polymer.
[0068] In yet another embodiment, the process involves providing a
polymer, and incubating the polymer in methylene chloride, or other
chemical, pharmaceutical, biologic agent, antibiotics,
antimicrobial or bacterial static metals or other agents, growth
factors, peptides, antibodies, viruses, RNAi, ceramic including but
not limited to hydroxyapatite and calcium phosphate in all size
ranges, metal including but not limited to titanium, Ti6Al4V, or
another polymer in a vacuum chamber under high vacuum conditions
effective to modify the surface of the polymer by introducing nano,
micron, and/or submicron scale features to the surface of the
polymer and coat or integrate the chemical, pharmaceutical,
antibiotic, antimicrobial or bacterio-static metal or other agent,
biologic agent, growth factors, peptides, antibodies, virus, RNAi,
ceramic, metal or another polymer to the polymer.
[0069] Alternatively, the polymer could have the above agents in
the polymer prior to the process.
[0070] In another aspect, the present invention relates to a
modified polymeric material produced according to the processes
described herein, as well as to implants containing the modified
polymeric material.
[0071] The present invention provides a robust method for producing
nanosurfaces and nanosurfaces with nano, submicron, and micron
scale features on polymers, including nanosurfaced
polyetheretherketone (PEEK) spine cages and nanosurfaced
polypropylene hernia meshes, polymer sutures and various polymers,
including those used for implants, biomaterials, or drug delivery
materials in any type of human or animal tissue.
[0072] The modified polymeric material of the present invention can
be used for both hard and soft tissue repair. In one aspect, the
invention is effective in developing nano-PEEK spine cages to treat
spine repair and other applications that use PEEK polymer.
Additionally, the invention provides nanosurfaced polypropylene
hernia meshes. The invention further provides an inexpensive and
consistent process that creates a nanosurface on polymers with a 2
or 3 dimensional geometry. The process of the present invention is
useful in that it is easily scalable, does not use chemicals, and
preserves the biocompatibility and mechanical properties of the
substrate material. Furthermore the nanosurface of the modified
polymeric material of the present invention can be useful in
improving or modifying biological responses, including protein or
antibody adsorption, cell attachment, cell function, and subsequent
tissue growth. The surface of the modified polymeric material of
the present invention can also improve therapeutic attachment and
delivery of various attachments, including, for example, peptides,
proteins, antibodies, drugs, metals, antimicrobial metals, biologic
tissues or agents, stem cells, modified cells, and the like.
[0073] The present invention also provides PEEK and polypropylene
surfaces that mimic natural tissues, and that may be more bioactive
and, thus, provide improved hard and soft tissue integration
markers compared to conventional PEEK and polypropylene surfaces.
As mentioned, the present invention provides a nano to nano and
micron rough surface.
[0074] With regard to biomedical uses, currently existing
conventional PEEK materials to treat spine repair possess smooth
material surface features. The same trend applies to polypropylene
based materials that are widely used in hernia repair applications.
Therefore, nano rough surface modification of such polymeric
materials, as provided by the present invention, is a new paradigm
for quick repair and surrounding tissue integration.
[0075] The present invention provides, in one aspect, a process for
preparing a modified polymeric material using simultaneous heat and
vacuum treatment on PEEK polymeric material (without chemical
process) to create nano rough surface without compromising the
mechanical, physical and chemical property of the polymer.
[0076] For polypropylene hernia meshes, the present invention
provides, in one aspect, a method that uses a high vacuum source in
the presence of pre-set mild heat or highly volatile methylene
chloride treatment. The methylene chloride has a very low boiling
point (less than 40.degree. C.; close to body temperature heat) and
can be removed spontaneously during the high vacuum treatment.
[0077] The present invention also relates to incorporating the
process for preparing a modified polymeric material into the PEEK
manufacturing process. This modified process can be useful for
creating a surface or pores in polymers (such as when the polymer
is molded/extruded for the first time).
[0078] The present invention also relates to using the process for
preparing a modified polymeric material to surfaces that are
already modified or will be modified thereafter. For example, the
present invention contemplates using the modified process of the
present invention to the top of a previously modified surface, and
also contemplates using another method (e.g., acid etching) to
further modify the modified surface after the process for preparing
the modified polymeric material to the surface is completed.
EXAMPLES
[0079] The following examples are intended to illustrate particular
embodiments of the present invention, but are by no means intended
to limit the scope of the present invention.
Example 1
Nano PEEK Spine Cages
[0080] As provided by the present invention, research and testing
has produced a nano surfaced PEEK without any chemical treatment,
but using high vacuum (in the range of 10.sup.-2 Torr to 10.sup.-6
Torr) and a temperature of 350.degree. C. at 15 min, 30 min, 60
min. The surface is novel and the processing method is novel.
[0081] FIG. 1 is a schematic of one embodiment of the nano PEEK
preparation method of the present invention. For example, PEEK
coupons were kept in the pre-heated (at 350.degree. C.) heating
oven for 15, 30, 60 min, respectively. Ceramic plates were used to
keep the coupons. After the above prescribed times, the samples
were immediately transferred to a vacuum chamber and high vacuum
was applied for 8 hours. Vacuum was released slowly and the PEEK
samples were characterized further. SEM analysis (see FIGS. 2-3)
and contact angle analysis experiments were performed and confirmed
the nano features on the modified surfaces and changed contact
angle values. Initial in vitro osteoblast cell data provided
information that increased cell function on samples treated at 60
min compared to other timing points and plain PEEK samples. EDS
spectra data was plain and nano PEEK samples (see FIG. 4). EDS data
revealed that PEEK surface before and after treatment showed the
same spectrum, indicating that there is no change in chemistry by
the nano treatment process.
[0082] Calcium deposition studies with osteoblast cell showed that
treated PEEK displayed significantly higher calcium after 1 w, 2 w,
and 3 w, although percentage of increase decreased with time (see
FIG. 5).
Example 2
Nano Polypropylene Hernia Mesh
[0083] As provided by the present invention, research and testing
has produced two different novel nano surfaced polypropylene based
hernia mesh scaffolds without any harsh chemicals (acids and
bases). For example, one approach used mild, easily removable
methylene chloride in combination with high vacuum (in the range of
10.sup.-2 Torr to 10.sup.-6 Torr). Additionally, a second nanorough
surface was produced on the polymer scaffolds at the same high
vacuum condition using a temperature of 60.degree. C. without any
chemical treatment. Both surfaces are novel and the processing
methods are novel.
[0084] The surface of the polymer scaffold is processed at high
vacuum (typically around at 10.sup.-6 Torr) with pre-set mild heat
(at 60.degree. C.) or with methylene chloride treatment without
heat treatment for 24 hours (see FIG. 6). For the treated samples,
polymer scaffolds were gradually brought down to atmospheric
pressure and temperature.
[0085] To look for the surface difference between the samples due
to the process illustrated in the depiction, Scanning Electron
Microscope (SEM) images were obtained using FEI NOVA nanoSEM FESEM
(FEI, Hillsboro, Oreg.) using low/high vacuum using through the
lens (TLD) secondary electron detector using low to high
magnification (10-200 k). Polymer scaffolds were mounted on copper
tape using silver paste for additional conductivity. They were
coated with Pt for 60 sec prior to imaging.
[0086] Accumulated charge from the electron beam was a problem but
was reduced due to the better conductivity provided by embedding
the mesh in silver paste.
[0087] Fine nano surface features were evident under above SEM
condition for treated samples compared plain samples (see FIG. 7).
The difference in the nanorough pattern reflects the two different
processes used with same polymer scaffold.
[0088] Therefore, the present invention is effective to produce at
least two different nanoroughness patterns on the same polymer
using a high vacuum process with pre-set mild heat treatment and
with methylyne chloride treatment.
Example 3
Calcium Deposition Results Using Osteoblast Cells
[0089] Calcium deposition studies with osteoblast cells were
conducted for various embodiments of the process of preparing
modified polymeric materials having micron and submicron surface
roughness. In particular, calcium deposition studies were conducted
using PEEK nanosurfaced using (i) a sulfuric acid etching technique
(PEEK 1) and (ii) a heat plus high vacuum technique (PEEK 2), as
described herein.
[0090] FIG. 8 illustrates the calcium deposition/osteoblast cell
results PEEK (untreated), nanoPEEK 1 (H.sub.2SO.sub.4 treated),
nanoPEEK 2 (heated at 350.degree. C. for 1 hour, followed by
vacuum), and glass after 1 w, 2 w, and 3 w.
[0091] Increased osteoblast adhesion correlates to enhanced
cell-to-cell contact which can promote osteoblast differentiation
to calcium depositing cells. Compared to untreated PEEK, this study
provided evidence of enhanced Ca deposition on both treated PEEK
after 3 weeks. While Ca deposition by both treated PEEK was not
different from glass surface, it was significantly greater compared
to plain PEEK surface. There are many possible reasons why Ca
deposition may be enhanced on these nano PEEK materials,
particularly with the invented nano-featured surfaces.
Specifically, compared to plain PEEK materials, nano PEEK materials
have greater surface areas and consequently higher numbers of atoms
at their surfaces.
Example 4
Nanosurfacing of Polymers Using Heat with Simultaneous Vacuum
[0092] As discussed elsewhere herein, in one aspect, the present
invention relates to a process for preparing a modified polymeric
material. Research was conducted on a particular embodiment of this
process (described below), where the process generally involved
subjecting polymers (targeted for nanosurfacing) to heat with
simultaneous vacuum.
[0093] In this example, the high vacuum treatment regimen included
loading polymer samples (i.e., PEEK) at 150.degree. C. and
subjecting the polymer to pump-down procedures to 10 mTorr
(pump/purge sequences). Thereafter, the polymer was subjected to a
ramp-up period during which the temperature was increased from
about 150.degree. C. to about 350.degree. C. over the course of
approximately 1 hour. The polymer was left at steady state for
about 1 hour (at 10 mTorr at 350.degree. C.). The polymer was then
subjected to a ramp-down period during which the temperature was
decreased to about 150.degree. C. over the course of 1 hour. The
sample was then extracted at 150.degree. C. and transferred to a
vacuum desiccator and stored under high vacuum for approximately 8
hours.
[0094] Results of the polymer nanosurfaces produced by this process
are shown in the SEM images of FIGS. 9-12 and 15, as compared to
"plain" polymer surfaces as shown in the SEM images of FIGS.
13-14.
[0095] Although preferred embodiments have been depicted and
described in detail herein, it will be apparent to those skilled in
the relevant art that various modifications, additions,
substitutions, and the like can be made without departing from the
spirit of the invention and these are therefore considered to be
within the scope of the invention as defined in the claims which
follow.
* * * * *