U.S. patent application number 14/806015 was filed with the patent office on 2016-01-28 for template for bacterial cellulose implant processed within bioreactor.
The applicant listed for this patent is Sofradim Production. Invention is credited to Yves Bayon, Philippe Gravagna, Sebastien Ladet, Olivier Lefranc.
Application Number | 20160022867 14/806015 |
Document ID | / |
Family ID | 42062544 |
Filed Date | 2016-01-28 |
United States Patent
Application |
20160022867 |
Kind Code |
A1 |
Bayon; Yves ; et
al. |
January 28, 2016 |
TEMPLATE FOR BACTERIAL CELLULOSE IMPLANT PROCESSED WITHIN
BIOREACTOR
Abstract
The present invention relates to an implant comprising: a sheet
of bacterial cellulose having a macro-pattern positioned on at
least a portion thereof. The invention also relates to a method for
making such an implant.
Inventors: |
Bayon; Yves; (Lyon, FR)
; Ladet; Sebastien; (Caluire & Cuire, FR) ;
Lefranc; Olivier; (Chatillon sur Chalaronne, FR) ;
Gravagna; Philippe; (Irigny, Charnoz, FR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Sofradim Production |
Trevoux |
|
FR |
|
|
Family ID: |
42062544 |
Appl. No.: |
14/806015 |
Filed: |
July 22, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13125607 |
Jul 11, 2011 |
9107978 |
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PCT/IB2009/007661 |
Nov 6, 2009 |
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14806015 |
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61112298 |
Nov 7, 2008 |
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Current U.S.
Class: |
428/156 |
Current CPC
Class: |
A61L 27/20 20130101;
Y10T 428/24479 20150115; A61L 27/50 20130101; A61F 2013/00255
20130101; A61F 13/00059 20130101; A61L 27/56 20130101; A61L 27/58
20130101; A61K 9/70 20130101; A61F 13/00012 20130101; A61F 13/00021
20130101; A61F 2013/00314 20130101; A61F 2013/00153 20130101 |
International
Class: |
A61L 27/20 20060101
A61L027/20; A61L 27/50 20060101 A61L027/50 |
Claims
1-5. (canceled)
6. An implant comprising: a sheet of bacterial cellulose having a
macro-pattern positioned on at least a portion thereof, wherein the
sheet includes pores of a size from about 0.5 to 5 mm and which do
not pass completely through the sheet.
7. The implant of claim 6, wherein the pores are from about 0.1 mm
to 3 mm in size.
8. The implant of claim 6, wherein the bacterial cellulose is
derived from Acetobacter xylinum.
9. The implant of claim 6, wherein the bacterial cellulose is
oxidized.
10. The implant of claim 9, wherein the bacterial cellulose is
oxidized with a degree of oxidation from 0.1 to 0.9.
11. The implant of claim 9, wherein the bacterial cellulose is
oxidized with a degree of oxidation from 0.2 to 0.65.
12. The implant of claim 9, wherein the bacterial cellulose is
oxidized by periodic acid or nitrogen dioxide.
13. The implant of claim 12, wherein the bacterial cellulose is
oxidized when the cellulose is at least partially purified and
depyrogenated.
14. The implant of claim 6, wherein the sheet is a generally planar
film.
15. The implant of claim 6, wherein the implant is
bioresorbable.
16. The implant of claim 6, wherein the pores comprise a shape
selected from the group consisting of circular, conical,
rectangular, square, oval, and, elliptical.
17. The implant of claim 6, wherein the pores are regularly
distributed circular openings.
18. The implant of claim 6, wherein the sheet is sterilized.
19. A bioresorbable implant comprising: a sheet of bacterial
cellulose which includes a first surface which allows tissue
integration and includes a macro-pattern positioned on at least a
portion thereof which includes pores which do not pass completely
through the sheet, and a second continuous, not indented surface
for the prevention of post-operative adhesions.
20. The bioresorbable implant of claim 19, wherein the pores are
from about 0.5 mm to 5 mm in size.
21. The bioresorbable implant of claim 19, wherein the pores are
from about 0.1 mm to 3 mm in size.
22. The bioresorbable implant of claim 19, wherein the bacterial
cellulose is derived from Acetobacter xylinum.
23. The bioresorbable implant of claim 19, wherein the bacterial
cellulose is oxidized.
24. The bioresorbable implant of claim 23, wherein the bacterial
cellulose is oxidized with a degree of oxidation from 0.1 to
0.9.
25. The bioresorbable implant of claim 23, wherein the bacterial
cellulose is oxidized by periodic acid or nitrogen dioxide.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/125,607 filed Jul. 11, 2011, now U.S. Pat.
No. 9,107,978, which is a National Stage Application of
PCT/1809/007661 filed Nov. 6, 2009, which claims benefit of U.S.
Provisional Application No. 61/112,298 filed Nov. 7, 2008, and the
disclosures of each of the above-identified applications are hereby
incorporated by reference in their entirety.
[0002] The implants described herein include a sheet of bacterial
cellulose having a macro-pattern positioned on at least one side of
the sheet.
[0003] Methods for producing such implants include culturing
bacteria capable of producing a bacterial cellulose in a bioreactor
in the presence of a template having a macro-patterned surface.
[0004] An aspect of the present invention is an implant
comprising:
[0005] a sheet of bacterial cellulose having a macro-pattern
positioned on at least a portion thereof.
[0006] The bacterial cellulose may derived from Acetobacter
xylinum. The bacterial cellulose may be oxidized.
[0007] Another aspect of the present invention is a method of
making an implant comprising:
[0008] providing a bioreactor having a macro-patterned surface;
and
[0009] culturing a bacteria on the macro-patterned surface, wherein
the bacteria is capable of producing a sheet of bacterial
cellulose.
[0010] The bacteria may be Acetobacter xylinum.
[0011] Another aspect of the present invention is a method of
treating a wound comprising contacting a wound with an implant as
described above.
[0012] FIG. 1 is a schematic perspective view of a template having
a three-dimensional macro-pattern according to an embodiment
described in the present disclosure.
[0013] FIG. 2 is schematic, cross-sectional view of a bioreactor
including a template and a porous sheet of bacterial cellulose
according to an embodiment described in the present disclosure.
[0014] FIG. 3 is a schematic perspective view of a porous sheet of
bacterial cellulose according to an embodiment described in the
present disclosure.
[0015] In the present disclosure, the term "implant" is intended to
mean a biocompatible or bioresorbable medical device, at least a
portion of which can be implanted in the human or animal body.
[0016] In the present disclosure, the term "bioresorbable" is
intended to mean the characteristic according to which an implant
and/or a material is degraded by the biological tissues and the
surrounding fluids, in vivo after a given period of time, that may
vary, for example, from one day to several months, depending on the
chemical nature of the implant and/or of the material.
[0017] In the present disclosure, the term "bioreactor" is intended
to include any device or system capable of supporting a
biologically active environment for growing or culturing materials.
In addition to containers or vessels capable of seeding or growing
bacteria, the bioreactors may also include the ability to provide
agitation, pressure changes, temperature controls, humidity
controls, media exchange, and ventilation.
[0018] In the present disclosure, the term "sheet" is intended to
include generally planar-shaped formats, such as films, foams,
pellicles, layers and combinations thereof.
[0019] In the present disclosure, the sheet of bacterial cellulose
may be produced from bacteria that synthesize cellulose. Cellulose
is synthesized by bacteria belonging to the genera Acetobacter,
Rhizobium, Agrobacterium, and Sarcina. Cellulose can be produced by
certain bacteria from glucose in the presence of oxygen, (such as,
for example, Acetobacter xylinum, referenced hereinafter as the
"bacteria"), in static conditions or in a bioreactor (see, e.g.
U.S. Pat. Nos. 4,912,049 and 5,955,326, the entire disclosures of
which are incorporated herein by this reference). Cellulose
suitable for use in the present implants can be obtained by the
fermentation of the bacteria. In embodiments, a derivative of the
cellulose is employed, such as oxidized cellulose resulting from
the oxidation of the cellulose by periodic acid or nitrogen
dioxide.
[0020] Bacterial cellulose possesses inherent characteristics which
allow effective promotion of wound healing (see, e.g. U.S. Pat. No.
7,390,492, the entire disclosures of which are incorporated herein
by this reference). In this regard, bacterial cellulose displays
properties (such as unique multi-layer three dimensional laminar
structures) that distinguish it from plant cellulose and other
natural polymeric materials. Bacterial cellulose shows excellent
wet strength, does not easily breakdown under compression and
demonstrates high moisture handling ability.
[0021] In the present disclosure, at least a portion of the sheet
of bacterial cellulose is porous and includes a macro-pattern
thereon. The porous sheet 100 is formed on or around a template 10
having a three dimensional ("3D") macro-pattern positioned within
the bioreactor 50. (See FIG. 2.) In embodiments, the template is
positioned on or near the bottom of the bioreactor. It should be
understood that instead of a separate structure positioned within
the bioreactor, the template may be formed directly into a surface
of the bioreactor, such as, for example, formed into the bottom
surface of the bioreactor. The porosity of the cellulose sheet is
created during the fermentation process when the cellulose is
synthesized by the bacteria in a bioreactor which includes culture
media. The cellulose synthesis on and around the template having
the 3D macro-pattern formed on at least a portion of the bioreactor
can lead to the sheet having a well-defined porosity. Because the
sheet is formed in the presence of the template, the macro-pattern
is imparted to the sheet during formation without the use of
additional processing.
[0022] The materials used to form the 3D macro-pattern on a
template of the bioreactor are compatible with the culture media,
the culture conditions and any other contents in the bioreactor
which allows for growth of the bacteria on the predetermined 3D
macro-pattern portion of the bioreactor. For example, the template
may be made from but not limited to poly(lactic acid), poly
(glycolic acid), poly (hydroxybutyrate), poly (phosphazine),
polyesters, polyethylene glycols, polyethylene oxides,
polyacrylamides, polyhydroxyethylmethylacrylate,
polyvinylpyrrolidone, polyvinyl alcohols, polyacrylic acid,
polyacetate, polycaprolactone, polypropylene, aliphatic polyesters,
glycerols, poly(amino acids), copoly (ether-esters), polyalkylene
oxalates, polyamides, poly (iminocarbonates), polyalkylene
oxalates, polyoxaesters, polyorthoesters, polyphosphazenes and
copolymers, block copolymers, homopolymers, blends and combinations
thereof, polychloride vinyle (PVC), polycarbonate, polysulfone,
fluorocarbones (eg. Teflon.RTM. and derivatives, Halar ECTFE
[ethylenechlorortrifluoroethylene copolymers)], Tefzel EFTE
[ethylene tetrafluorethylene], polyfluoride vinyle [PVDF],
stainless steel. The 3D macro-pattern on the template can be
designed having any form, geometry or topography which allows for
removal of the implant from the bioreactor surface following the
biosynthesis of the bacterial cellulose. The materials used to
design the 3D macro-pattern, such as peaks, tubes, rods, and
spikes, have the ability to withstand the growth of the bacterial
cellulose thereby creating a macro-pattern, while retaining a
softness and flexibility in order to allow the bacterial cellulose
to be withdrawn from the bioreactor without damaging the
macro-pattern. For example, as seen in FIG. 1, 3D macro-pattern 10
includes a series of regularly spaced rods 15.
[0023] The macro-pattern may create pores, openings or perforations
in the sheet having any geometric shape or dimension. For example,
the pores may be circular, conical, rectangular, square, oval,
elliptical, polygonal and the like. The macro-pattern on the
bacterial cellulose sheet improves the implants ability to
integrate tissue. As seen in FIG. 3, sheet 100 includes regularly
distributed circular openings 120 resulting from culturing bacteria
in the presence of the 3D macro-pattern shown in FIG. 1.
[0024] The size of the pores may be from about 0.5 mm to 5 mm, in
embodiments from about 1 mm to 3 mm.
[0025] It should be understood that the macro-pattern needs not
pass completely through the sheet (e.g., holes), but rather may be
indententions resulting from the sheet being formed around and over
at least a portion of the macro-pattern template. In such
embodiments, the sheet may have a continuous, not indentented
surface for the prevention of post-operative tissular
adhesions.
[0026] In other embodiments, it should be understood that the
macropattern may pass completely through the sheet (e.g., full
thickness holes).
[0027] The implants described herein are useful for implantation
where soft tissues are in need of repair, reinforcement,
replacement or augmentation. For instance, the implants may be
useful near the abdominal wall, vascular tissue or the pelvic
floor. The implants may be easily fixed for surgeries, by any known
techniques, among them suturing, stitching, stapling and
tacking.
[0028] In embodiments, the bacterial cellulose is harvested at the
end of the fermentation of the bacteria. The harvested cellulose is
subjected to purification and depyrogenation processes. The
bacterial cellulose may be oxidized by periodic acid or by nitrogen
dioxide before, after, or during the purification and
depyrogenation process. In embodiments, the bacterial cellulose may
be oxidized when the cellulose is at least partly purified and
depyrogenated. The final level of oxidation can be controlled in
such a way to produce a resorption time of from several days to
several months. The degree of oxidation can be from about 0.1 to
about 0.9, in embodiments from about 0.2 to about 0.65.
[0029] Other chemical modifications of the bacterial cellulose for
the generation of cellulose derivatives are also within the scope
of the present disclosure. Cellulose belong to the family of
biodegradable, renewable polymers that provides a broad range of
important functional properties, and are thus widely used in
industry today. However, some of the inherent properties of these
polysaccharides limit their utility in certain applications.
Therefore, native cellulose are commonly modified by physical,
chemical, enzymatic or genetic means in order to obtain specific
functional properties (Richardson, et al., Analytica Chimica Acta,
2003; Kennedy, et al., Cellulose and its Derivatives: Chemistry,
Biochemistry and Applications, Ellis Horwood, Chichester, 1985;
Guilbot, et al., The Polysaccharides, G. Aspinall (Ed.), Academic
Press, New York, 1985). Native cellulose has an intrinsic lack of
solubility in water and most organic solvent systems which
constitutes a major obstacle for utilizing cellulose in many
industrial applications. It may be a goal to chemically derivatize
the bacterial cellulose in such a way to obtain derivatives soluble
in organic solvents, for an easier remodeling of the bacterial
cellulose, for example.
[0030] The present implants which include a bacterial cellulose
sheet having a 3D macro-pattern may advantageously maintain one or
more of the original properties of bacterial cellulose sheets (such
as, for example, high biocompatibility, extreme hydrophilicity,
unique multi-layered three dimensional laminar structures which
provide its moisture handling properties, excellent wet strength,
high resistance to breakdown under compression, conformability,
absence of generation of harmful particles of the cellulose mesh
after rubbing against surrounding tissues or erosion at sharp edges
of tissues--e.g., sharp edges of bone and cartilage tissues) while
inducing controlled porosity directly during the biosynthesis
within the sheets for better tissue integration and cell
colonization when implanted. Bacterial cellulose sheets can have
superior mechanical properties compared to other bioresorbable
implants.
[0031] Medical implants in accordance with this disclosure may be
produced at a predetermined size or produced in large sheets which
may be cut to sizes appropriate for the envisaged application. The
medical implants may be packaged in single or dual pouches and
sterilized using conventional techniques, such as, but not limited
to, irradiation with beta (electronic irradiation) or gamma
(irradiation using radioactive cobalt) rays at about 25 KGy to
about 35 KGy, and/or sterilized by ethylene oxide.
[0032] It will be understood that various modifications may be made
to the embodiments disclosed herein. Thus, those skilled in the art
will envision other modifications within the scope and spirit of
the disclosure.
* * * * *