U.S. patent application number 13/406424 was filed with the patent office on 2012-08-30 for materials for soft and hard tissue repair.
This patent application is currently assigned to OBI BIOLOGICS, INC.. Invention is credited to Barry K. Bartee, Richard A. Rosen.
Application Number | 20120221118 13/406424 |
Document ID | / |
Family ID | 46719533 |
Filed Date | 2012-08-30 |
United States Patent
Application |
20120221118 |
Kind Code |
A1 |
Bartee; Barry K. ; et
al. |
August 30, 2012 |
MATERIALS FOR SOFT AND HARD TISSUE REPAIR
Abstract
Biomaterials and methods and uses for repair or augmentation of
tissues are provided. In particular, the invention provides a
multi-layered, naturally occurring multi-axial oriented biomaterial
comprising predominately type I collagen fibers. The invention
further provides methods and uses for repair or augmentation of
tissues using biomaterials of the invention.
Inventors: |
Bartee; Barry K.; (Lubbock,
TX) ; Rosen; Richard A.; (Lubbock, TX) |
Assignee: |
OBI BIOLOGICS, INC.
Lubbock
TX
|
Family ID: |
46719533 |
Appl. No.: |
13/406424 |
Filed: |
February 27, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61446956 |
Feb 25, 2011 |
|
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61515803 |
Aug 5, 2011 |
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Current U.S.
Class: |
623/23.72 |
Current CPC
Class: |
A61F 2/0063 20130101;
A61L 2430/02 20130101; A61L 27/50 20130101; A61L 2300/608 20130101;
A61L 27/34 20130101; A61L 31/14 20130101; A61L 27/38 20130101; A61L
2430/34 20130101; A61L 31/044 20130101; A61L 31/16 20130101; A61L
2300/414 20130101; A61L 27/24 20130101; A61L 31/005 20130101; A61L
27/54 20130101 |
Class at
Publication: |
623/23.72 |
International
Class: |
A61F 2/02 20060101
A61F002/02 |
Claims
1. A multi-layered, naturally occurring multi-axial oriented
biomaterial comprising predominately type I collagen fibers,
wherein the biomaterial is suitable for tissue repair or
augmentation.
2. The biomaterial of claim 1, wherein the biomaterial is derived
from a mammalian source.
3. The biomaterial of claim 1, wherein the biomaterial is derived
from a non-human source.
4. The biomaterial of claim 2 or 3, wherein the mammalian or
non-human source comprises a porcine, a bovine, an ovine, an equine
or a hircine.
5. The biomaterial of any of claims 1 to 3, wherein the biomaterial
comprises multiple layers of tendinous, aponeurotic fibrous
collagen, optionally wherein the type I collagen fibers are
multi-axial oriented.
6. The biomaterial of any of claims 1 to 3, wherein the biomaterial
is derived from a dense fibrous, aponeurotic layer of a mammalian
or non-human body or tissue source.
7. The biomaterial of claim 6, wherein the mammalian or non-human
body or tissue source mimics a connective tissue or abdominal wall
of a mammal, human or non-human body.
8. The biomaterial of claim 6, wherein the mammalian tissue source
mimics the naturally oriented fibers of the anterior abdominal wall
of a mammal, human or non-human body.
9. The biomaterial of any of claims 1 to 3, wherein the biomaterial
comprises a multi-density construct derived from one or more of
dermis, rectus sheath fascia, shoulder, hind and/or forequarter
tissues.
10. The biomaterial of any of claims 1 to 3, wherein the
biomaterial has been processed, modified or treated to reduce the
amount of cells, fat, protein, nucleic acid, non-collagenous and/or
antigenic components in the mammalian or non-human source from
which the biomaterial was derived.
11. The biomaterial of any of claims 1 to 3, wherein the
biomaterial is substantially free of cells, nucelic acids,
non-collagenous proteins, and/or antigenic components in the
mammalian or non-human source from which the biomaterial was
derived.
12. The biomaterial of any of claims 1 to 3, wherein the
biomaterial has been cleaned, decellularized, or de-fatted, or
processed to remove non-collagenous proteins, cells, nucelic acids
or antigenic components present in the mammalian or non-human
source from which the biomaterial was derived.
13. The biomaterial of any of claims 1 to 3, wherein the
biomaterial has been purified or lyophilized.
14. The biomaterial of any of claims 1 to 3, wherein the
biomaterial is suitable for soft or hard tissue repair.
15. The biomaterial of claim 1, wherein the biomaterial is
perforated for improved tissue grafting or integration.
16. The biomaterial of claim 1, wherein the biomaterial is
cross-linked or not cross-linked.
17. The biomaterial of claim 1, wherein the biomaterial is
cross-linked by chemical modification.
18. The biomaterial of claim 16 or 17, wherein the cross-linked
biomaterial has increased resistance to tearing, degradation, creep
and attenuation under functional loading.
19. The biomaterial of any of claims 1 to 3, wherein the
biomaterial comprises at least 2, 3, 4 or more layers.
20. The biomaterial of claim 1, wherein the biomaterial comprises a
soft or hard tissue repair, reinforcing or augmenting graft or
implant.
21. The biomaterial of any of claims 1 to 3, wherein the
biomaterial comprises or is formed into a multi-component, or
coated, fused or layered construct, with one or more second
materials.
22. The biomaterial of claim 21, wherein the second material
comprises a synthetic or biologic hard, semi-soft or soft, flexible
or rigid, mesh, implant, graft, or prosthesis.
23. The biomaterial of claim 22, wherein the mesh comprises an
absorbable polymer mesh.
24. The biomaterial of claim 21, wherein the second material
comprises a polymer material or an absorbable layer designed to
limit, prevent, reduce or retard adhesion formation.
25. The biomaterial of claim 21, wherein the polymer material
comprises a polyglycolide, polydioxanone, polypropylene (PP),
polyester, polytetrafluoroethylene (PTFE), expanded
polytetrafluoroethylene (ePTFE), and/or polyetheylene-terephthalat
(PET).
26. The biomaterial of claim 21, wherein the second material
comprises a material that provides the biomaterial with increased
or additional strength.
27. The biomaterial of claim 21, wherein the second material
improves or increases integration, grafting, durability or
stability of the biomaterial when integrated into or combined with
tissue of a mammalian, human or non-human recipient.
28. The biomaterial of claim 21, wherein the second material
comprises mammalian cells that are autologous or are a xenograft
with respect to the source of the biomaterial, or are autologous or
are a xenograft with respect to the recipient of the
biomaterial.
29. The biomaterial of claim 28, wherein the cells comprises dermis
cells, or stem cells, fibroblasts, myoblasts, myocytes, edothelial
cells, immune cells (macrophages, monocytes), osteoblasts, or
chondroblasts.
30. The biomaterial of claim 21, wherein the second material
comprises a scaffold or lattice.
31. The biomaterial of claim 21, wherein the second material
comprises an autologous or recombinant growth factor, chemokine or
cytokine.
32. The biomaterial of claim 21, wherein the second material
comprises a bone morphogenic protein (BMP).
33. The biomaterial of claim 21, wherein the second material
comprises platelet derived growth factor (PDGF), epidermal growth
factor (EGF), insulin like growth factor (IGF)-1, fibroblast growth
factor (FGF), transforming grow factor (TGF)-beta, bone morphogenic
protein (BMP)-2, BMP-3, BMP-4, or BMP-7.
34. The biomaterial of claim 1, wherein the biomaterial is
multilaminar.
35. The biomaterial of claim 1, wherein the biomaterial is
multidirectional with regard to fiber orientation of the
collagen.
36. The biomaterial in claim 1, wherein the biomaterial has a
plurality of pores, wherein the pores aid in tissue grafting or
integration or reducing or decreasing adhesion formation.
37. The biomaterial of claim 1, wherein the biomaterial has a
thickness of between 0.2 mm and approximately 5.0 mm.
38. The biomaterial of claim 1, wherein the biomaterial has a
suture retention strength from between 4-150 Newtons (N).
39. The biomaterial of claim 1, wherein the biomaterial has a
suture retention strength of at least 20 N.
40. The biomaterial of claim 1, wherein the biomaterial has a tear
resistance of between 5 to 100N.
41. The biomaterial of claim 1, wherein the biomaterial has a
uniaxial or a multiaxial tensile strength of at least 20 N.
42. The biomaterial of claim 1, wherein the biomaterial has ball
burst tensile strength of 25 to 1200 N/cm.
43. The biomaterial of claim 1, wherein the biomaterial has ball
burst tensile strength of greater than 50 N/cm.
44. The biomaterial of claim 1, wherein the biomaterial ball burst
strain (at a stress of 16N/cm) is in the range of 5% to 35%.
45. The biomaterial of claim 1, wherein the biomaterial has a first
rough side and an opposing second dense side.
46. The biomaterial of claim 1, wherein the first rough side
provides for cell ingrowth in a recipient.
47. The biomaterial of claim 1, wherein the second dense side
provides for reduced cell ingrowth or adhesion to viscera or bowel
of a recipient.
48. The biomaterial of claim 1, wherein the tissue comprises
connective tissue.
49. The biomaterial of claim 1, wherein the biomaterial may be cut,
configured, formed or shaped without substantial loss of collagen
fiber integrity, substantial disruption of collagen fiber
orientation or substantial loss of strength.
50. The biomaterial of claim 1, wherein the biomaterial comprises a
quilted, stitched, sutured, or attached multi-layer construct, a
predominantly flat, oval, circular, or rectangular, folded or
rolled sheet.
51. The biomaterial of claim 50, wherein the multi-layer construct
is formed by welding, joining or gluing with an adhesive.
52. The biomaterial of claim 1, wherein the biomaterial comprises a
plurality of biomaterial elements stitched, sutured, joined or
quilted together to increase size or thickness.
53. The biomaterial of claim 1, wherein the biomaterial is cut,
configured, formed or shaped for deployment as a hernia repair
implant, for repair of a body cavity defect, or to strengthen,
augment or reinforce weakened, attenuated tissues, or tissues
damaged as a result of disease, trauma or surgery.
54. A method for repair or augmentation of a tissue of a recipient
mammalian subject in need of repair or augmentation, comprising
attaching, joining or affixing thereto the biomaterial of any of
claims 1 to 53 to the tissue of the recipient mammlian subject in
need of repair or augmentation.
55. A method for closure or repair of a wound or cavity in a tissue
of a recipient mammlian subject, comprising: a) providing a
biomaterial of any of claims 1 to 53; b) contacting the wound with
the biomaterial, or positioning, shaping or contouring the
biomaterial over the cavity, or introducing the biomaterial into
the cavity; c) joining, attaching or affixing the biomaterial to
the wound or cavity to secure said biomaterial; and d) closing said
cavity or repairing said wound in the tissue.
56. A method of repairing a defect or augmenting a tissue of a
recipient mammlian subject in need thereof, comprising: (a)
positioning, shaping or contouring the biomaterial of any of claims
1 to 53 to cover a defect or augment the tissue in need thereof;
and (b) securing the biomaterial in place.
57. A method for tissue repair or augmentation comprising
delivering to tissue of a recipient mammlian subject a biomaterial
of any of claims 1 to 53, wherein the biomaterial serves to repair
or augment the tissue.
58. The method of any of claims 54 to 57, wherein the tissue
repaired or augmented comprises a soft or hard tissue.
59. The method of any of claims 54 to 57, wherein the tissue
repaired or augmented comprises muscle or abdominal wall.
60. The method of any of claims 54 to 57, wherein the recipient
mammlian subject has an abdominal wall defect, trauma, damage, or
weakness, a hernia, a fistula, or torn or damaged dura.
61. The method of claim 60, wherein the hernia comprises a ventral
incisional hernia; a umbilical, inguinal, femoral, spigelian,
parastomal or hiatal hernia; a diaphragmatic hernia; or a lumbar
triangle hernia.
62. The method of any of claims 54 to 57, wherein the recipient
mammlian subject is in need of pelvic floor reconstruction; in need
of repair, reinforcement or augmentation of esophageal perforations
or defects; in need of a protective barrier between vascular
anastamosis and bowel; in need of a protective barrier between
viscera following repair; in need of correction or surgery for
rectal prolapse; in need of maxillofacial, periodontal or dental
surgery: as a soft tissue augmentation material or in the repair of
hard and/or soft tissue defects; in need of skeletal defect repair;
in need of orthopedic surgery; in need of urologic surgery; in need
of gynecologic surgery; in need of plastic surgery; or in need of
neurosurgery.
63. The method of any of claims 54 to 57, wherein the recipient
mammlian subject is in need of a protective barrier between
proximal aortic anastamosis and bowel, as encountered following
aortic reconstruction utilizing prosthetic vascular grafts; in need
of a protective barrier between viscera following repair of
rectovaginal fistula, rectovesicle fistula; in need of skeletal
defect repair in the craniomaxillofacial or axial skeleton; in need
of orthopedic surgery for joint repair or replacement or in soft
tissue repair or augmentation of joints or to reinforce, augment,
replace weakened, injured, attenuated or diseased ligamentous or
joint structures; in need of urologic surgery for stress urinary
incontinence or organ prolapse; in need of gynecologic surgery to
correct or reinforce for pelvic floor weakness, as in rectocele,
cystocele, vaginal prolapse; in need of plastic surgery to support
or reinforce, inhibit or limit migration of implanted prosthesis,
reinforce or augment defects or areas of weakness created by
mobilization of soft tissues used in various reconstructive
procedures, or to create, alter or manipulate body contours; or in
need of neurosurgery for dural replacement and/or patche of a dural
defect.
64. The method of any of claims 54 to 57, wherein the biomaterial
is a xenograft with respect to the recipient mammalian subject.
65. The method of any of claims 54 to 57, wherein the biomaterial
further comprises cells or proteins that are autologous with
respect to the recipient mammalian subject.
66. A method for manufacture of a biomaterial suitable for tissue
repair or augmentation comprising: (a) obtaining a multi-layered,
naturally occurring multi-axial oriented biomaterial comprising
predominately type I collagen fibers; and (b) processing, modifying
or treating the biomaterial to be suitable as a xenograft in human
and non-human mammal tissue repair or augmentation.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority Application
Ser. No. 61/446,956, filed on Feb. 25, 2011, and Application Ser.
No. 61/515,803, filed on Aug. 5, 2011, both of which applications
are expressly incorporated herein by reference in their
entirety.
FIELD
[0002] The invention relates to biomaterials and methods and uses
for tissue repair or augmentation.
INTRODUCTION
[0003] Collagen rich, naturally derived tissue has been used to
repair hernias and large abdominal wall defects for many years. The
use of autologous human fascia lata to repair hernia defects was
reported by Kirschner in 1913. Fascia lata, a dense layer of
collagen rich connective tissue, was taken from a donor site on the
lateral (outside) aspect of the thigh along with the accompanying
blood vessels, and transplanted to the defect. This type
transplant, with the patient being both the donor and recipient, is
known as an autologous transplant. If there are no blood vessels
brought with the tissue and where circulation is re-established by
connection of the blood vessels, it is known as a "free graft" or
transplant. If the blood vessels are brought along, and
reconnected, it is known as a "vascularized graft" or transplant. A
major disadvantage to this type of procedure however, in addition
to the large surgical procedure required to harvest the tissue, is
the risk donor site morbidity such as lateral knee instability.
Indeed, studies indicate that this procedure has a high post
operative complication rate in the range of 10% to 40%. Recurrent
hernia occurred in 10 to 25% of patients followed for up to 29
months using this procedure. One possible reason for the failure in
this technique is that autologous tissues, especially if not
vascularized, can be readily resorbed. The inherent limitations of
autologus tissues for soft tissue repair led to the development and
widespread use of synthetic prosthetic mesh materials for hernia
and abdominal wall defect repair.
[0004] There may as many as 5 million laparotomies performed yearly
in the United States, and approximately 20% result in incisional
hernias. Approximately a quarter of a million ventral incisional
hernias are repaired annually. These figures do not take into
account other hernias such as femoral, inguinal umbilical,
parastomal, hiatal, diaphragmatic and Spigelian. Prosthetic mesh
repair, instead of suture alone, reduces recurrence risk by
approximately 50%.
[0005] Synthetic hernia repair meshes for many years have
represented the Gold Standard for surgical repair. The so-called
"heavyweight" synthetic meshes represent the first generation of
products. These products are not without their problems, which
include infection, scar formation and pain, adhesion formation with
viscera leading to bowel obstruction and fistula. These problems
have lead to the development of a variety of synthetic and biologic
materials for repair of soft tissue defects, weaknesses, hernias or
inadequacies. Currently, several synthetic meshes including
polypropylene (prolene), polyester and polytetrafluoroethylene
(PTFE) are used. Some of these polymers have recently been
manufactured in combination with a variety of partially absorbable
coatings, designed to limit adhesion formation and the attendant
complications. In addition, it has become evident that strength
alone is not the most important feature in a hernia mesh, but
rather the flexibility and compliance with the body wall are
important as well. In an attempt to alleviate some of the problems
associated with the "heavyweight" synthetics, so-called
"lightweight" synthetic meshes have been introduced. These
typically have reduced tensile strength compared to heavyweight
mesh, but have increased flexibility and greater compliance, with
the biomechanical characteristics closer to the abdominal wall.
[0006] The drawbacks associated with the synthetic meshes (both
heavyweight and lightweight) have lead to the development of
"biologic" meshes. These products are derived from tissues such as
acellular human dermal matrix, acellular animal (porcine or bovine)
dermal matrix, as well as from porcine small bowel submucosa. A
major advantage of the biologic meshes compared to the synthetics
is a reduction in the risk of post-operative infection, reduced
bowel adhesions and/or fistula formation. However, once in
widespread use, the biologics have been shown to have their own
drawbacks: namely laxity and recurrence of hernia over time. Over
the past few years, the problems with these materials have become
apparent and re-operation for secondary repair has been required in
some cases. To address these issues, it would be advantageous to
have a biologic hernia repair material with the advantages and
properties of the current biologic meshes, namely a reduction in
infection risk and reduction of adhesion risk, while simultaneously
possessing the biomechanical advantages and properties of the
current synthetic meshes.
[0007] An adjunctive technique to repair hernias large abdominal
wall defects include the use of component separation (CST). In CST,
the muscle and fascia layers of the patient's abdominal wall are
separated by dissection and in some cases transection of the muscle
and fascial layers, and the muscle layers and/or fascial layers are
advanced toward the midline to close large abdominal wall defects.
While CST may be used alone to achieve closure, it also may be used
in conjunction with synthetic or natural prosthetic patch materials
to not only increase the ability to close large defects, but also
to reduce tension on the closure, leading to decreased risk for
recurrence.
SUMMARY
[0008] The invention provides a multi-layered, naturally occurring
multi-axial oriented biomaterial comprising predominately type I
collagen fibers, wherein the biomaterial is suitable for tissue
repair or augmentation. The invention further provides methods and
uses for repair or augmentation of a tissue of a recipient
mammalian subject (mammalian or non-mammalian) in need of repair or
augmentation utilizing the biomaterial of the invention. The
invention yet further provides methods and uses for manufacture of
a biomaterial suitable for tissue repair or augmentation.
DESCRIPTION OF THE DRAWINGS
[0009] FIGS. 1(a) and (b) illustrate the muscle and fascial layers
of the human abdominal wall: (a) illustrates the abdominal wall
above the arcuate line, where the vertically oriented rectus
abdominus is covered anteriorly and posteriorly by fascia
consisting of a combination of all three distinct muscle layers
namely the external oblique, the internal oblique, and the
transversus abdominis; and (b) illustrates the abdominal wall below
the arcuate line, where the rectus abdominus muscle is covered
anteriorly only by fascia, thereby making a very dense, strong
connective tissue layer with fibers oriented in multiple
directions.
[0010] FIG. 2 shows the rectus fascia fiber orientation of a human
abdominal wall.
[0011] FIGS. 3(a) to (f) are SEM photographs of decellularized and
lyophilized biomaterial obtained as described herein showing (a)
porcine rectus sheath fascia surface, (b) porcine rectus sheath
fascia cross-sectional view, (c) bovine shoulder fascia collagen
surface view, (d) porcine dermis surface, (e) bovine shoulder
fascia layers (100.times. magnification), (f) bovine shoulder
fascia layers (250.times. magnification), and (g) bovine shoulder
fascia collagen with H&E stained sections (40.times. and
100.times. magnifactions).
[0012] FIG. 4 shows a saggital section of a pre-laparascopic hernia
repair view of an abdominal wall with bowel incarcerated in hernia
defect according to embodiments of the invention.
[0013] FIG. 5 shows a saggital section of a post-laparascopic
hernia repair view of a small intestine withdrawn from the
abdominal wall defect with subsequent coverage of the defect
utilizing the invention.
[0014] FIG. 6 shows a post-laparascopic hernia repair view
illustrating the biomaterial has been surgically secured to the
abdominal wall and covering the hernia defect according to the
invention.
[0015] FIG. 7 shows thickness measurements of an exemplary bovine
fascia biomaterial according to the invention by a laser
micrometry.
[0016] FIG. 8 shows suture retention strength measurements of an
exemplary bovine fascia biomaterial according to the invention.
[0017] FIG. 9 shows tear resistance measurements of an exemplary
bovine fascia biomaterial according to the invention.
[0018] FIGS. 10(a) and 10(b) show ball burst testing results of an
exemplary bovine fascia biomaterial according to the invention.
[0019] FIG. 11(a) shows an image of a pre-repair of a hernia defect
according to the invention. FIG. 11(b) shows an image of a
post-repair of a hernia defect according to the invention.
DETAILED DESCRIPTION
[0020] The invention provides biomaterials, and methods and uses of
biomaterials for tissue repair or augmentation. Invention
biomaterials are suitable for repair or augmentation of soft or
hard tissues, such as abdominal wall, muscle, orthopedic
applications, etc. The biomaterial is a naturally occurring,
multi-layered and multi-axial oriented containing predominately
collagen, e.g., type I collagen. The term "collagen" as used herein
refers to all forms of collagen, including those which have been
processed or otherwise modified. Optionally, the type I collagen
fibers may be multi-axial oriented. In certain embodiments, the
biomaterial is multi-laminar. In certain embodiments, the
biomaterial is multi-directional with regard to fiber orientation
of the collagen fibers. For example, the fibers have a
multi-directional (axial) orientation, and all fibers are not all
parallel to each other. The multi-directional (axial) fiber
orientation provides additional strength to the biomaterial. In
various embodiments, the interdigitation of the collagen fibers are
arranged at angles, such as between 1 and 359 degrees relative to
another fibers, for example, between 45 and 90 degrees relative to
one another.
[0021] In various embodiments, the biomaterial is derived from a
mammalian source or a non-human source, such as a porcine, a
bovine, an ovine, an equine, a hircine, or any suitable mammal
source. In certain embodiments, the biomaterial includes a
multi-density construct derived from one or more of dermis, rectus
sheath fascia (e.g., rectus abdominis fascia), shoulder, hind
and/or forequarter tissues. In certain embodiments, the biomaterial
is derived from dense fibrous, aponeurotic layers of a mammalian
body or non-human body or tissue source, for example, an oriented
fibrous structure of fascia (i.e., porcine rectus sheath, bovine
forequarter fascia), or fascia lata. In certain embodiments, the
biomaterial includes connective tissue, which comprises a collagen
scaffold, optionally free of muscle cells.
[0022] The biomaterial is intended to mimic one or more of
physiomechanical, biomechanical, and/or anatomical properties of a
natural tissue. The mammalian or non-human body or tissue source
may mimic the architecture and physicomechanical characteristics of
the tissue being repaired, for example, the abdominal wall of a
mammal, human or non-human body. In certain embodiments, the
mammalian or non-human body or tissue source may mimic a connective
tissue, or naturally oriented fibers of the abdominal wall (e.g.,
anterior abdominal wall) of a mammal, human or non-human body. In
certain embodiments, the biomaterial is constructed of multiple
layers of tendinous, aponeurotic fibrous collagen from diverse
mammalian tissue sources forming diverse tissue construct mimicking
the naturally oriented fibers of the anterior abdominal wall. As
such, the biomaterial may exhibit various properties of an
abdominal wall. The biomaterial may mimic the composition and
structure of an abdominal wall. The biomaterial may conform to the
abdominal wall anatomy.
Anatomy of the Abdominal Wall
[0023] The intact rectus sheath consists of multiple layers of
strong, dense, fibrous fascial layers of primarily type I collagen
which eventually encircle the central muscular pillar of the
abdomen, the rectus abdominis muscle. Moreover, these
musculofascial layers of the anterior abdominal wall are oriented
in three separate and distinct directions with respect to the
midline of the abdomen, an arrangement designed to withstand
loading from multiple directions.
[0024] The external oblique muscle is the outermost muscular layer.
It originates from the lower aspect of the ribs and courses
inferio-medially where it forms a fibrous aponeurosis and attaches
at the linea alba. Both of the external oblique aponeurotic laminae
course anterior to the rectus abdominis muscle above and below the
arcuate line. These aponeurotic fibers of the external oblique are
oriented at 45 degrees with respect to the vertical midline.
[0025] The internal oblique musculofascial layer originates from
the anterior iliac crest, the inguinal ligament and the posterior
aponeurosis of the transversus abdominis muscle. The
musculotendinous fibers of the internal oblique run
superio-medially at a 90 degree angle to the external oblique
layer, inserting on the cartilages of the lower ribs. At the
lateral border of the rectus abdominis muscle and above the arcuate
line, the aponeurosis of the internal oblique splits into two
laminae, one course anterior to the rectus abdominis, the other
laminae posterior, encircling the rectus abdominis muscle,
contributing to both the anterior and posterior rectus sheaths
(FIG. 1a). Below the arcuate line, the internal oblique aponeurosis
does not split, and both laminae course anteriorly along with both
laminae of the transversus abdominis forming the anterior rectus
sheath (FIG. 1b). The inferior aponeurotic fibers then pass beneath
the spermatic cord, pass through the inguinal canal and descend
posterior to the superficial ring to attach to the pubic crest. The
most inferior fibers of the aponeurosis fuse with the aponeurosis
of the transversus abdominis to form the conjoint tendon, which
courses inferiorly to insert on the pubic crest.
[0026] The innermost layer, the transverse abdominis layer, runs
horizontally at a 90 degree angle with respect to the midline,
intersecting the external and internal oblique layers at a 45
degree angle. This muscle originates at the iliac crest and
inguinal ligament inferiorly, the inner surface of the lower costal
cartilages superiorly and has a fibrous origin from the transverse
processes of the lumbar vertebra bilaterally. These fibers all run
medially to insert at the lateral border of the rectus muscle.
Above the arcuate line, the insertion forms an aponeurosis,
contributing to the posterior rectus sheath.
[0027] The rectus muscles are vertically oriented, paired muscles
forming the principle vertical muscle column of the anterior
abdominal wall. Inferiorly, the rectus muscle originates from the
pubic symphysis and pubic crest. It inserts superiorly on the
xiphoid process and the costal cartilages of the lower ribs. The
lateral border of each rectus and its sheath merge with the
aponeurosis of the external oblique muscle laterally to form the
linea semilunaris, a dense collection of tendinous fibers running
vertically at the lateral border of the rectus sheath. Toward the
midline, the aponeurotic layers coalesce forming another dense
vertical teninous band of collagen, the linea alba,
[0028] Due to the unique and optimal orientation of the collagen
fibers within these fascial layers and in conjunction with the
associated paired muscles, the intact abdominal wall provides core
strength protection to vital organs, as well as stabilizes and
facilitates movement and posture of the trunk.
[0029] In the invention, suitable fascia may be harvested either
above or below the arcuate line of an abdominal wall of a mammalian
or non-human source.
[0030] The rectus fascia fiber orientation of a human abdominal
wall is shown in FIG. 2. The three layers, namely internal oblique
aponeurosis, external oblique aponeurosis and transversus abdominus
aponeurosis, are enlarged on the right hand side of the figure
showing that the fiber structures are oriented at right angles to
one another. When a hernia occurs, a defect occurs in one or more
of these layers. To repair a hernia defect, a material must be
strong enough to withstand intraabdominal pressure and the forces
applied to the abdominal wall tissue during everyday activity.
[0031] The invention employs a fascia, either from the abdominal
wall of a mammalian or non-human source such as a pig, or a cow
(e.g. the shoulder region of a cow), or a horse. The rectus fascia
fiber orientation of the abdominal wall of a mammlian or non-human
is similar in architecture as that of the human. These fascial
tissues are decellularized and optionally freeze-dried prior to
implantation to reduce antigenicity, serving as a biological
implant with fiber architecture and orientation similar to the
tissue that is being repaired.
[0032] Certain embodiments of the invention provide a biomaterial
derived from a mammalian or a non-human fascia. Fascia is composed
of strong, thick collagen fibers aligned along lines of stress
similar to the human abdominal wall. Unlike dermis, it composes of
smaller, randomly oriented collagen fibers. For comparison and
illustration purposes, Scanning Electron Microscopy (SEM) was
conducted on scaffolds of porcine fascia, bovine fascia and porcine
dermis, and the SEM images are shown in FIGS. 3(a)-(f).
[0033] FIG. 3(a) shows a decellularized and lyophilized porcine
rectus sheath fascia surface (70.times. magnification). The
apparent porosity (open structure) is suitable for cell and tissue
ingrowth. FIG. 3(b) shows a decellularized porcine rectus sheath
fascia in cross section (70.times. magnification). The laminar and
fibrous structures are shown. There are three distinct layers where
each layer appears to have a separate orientation, which is
consistent with the anatomical organization of rectus sheath
fascia. FIG. 3(c) shows a decellularized and lyophilized bovine
shoulder fascia collagen surface (50.times. magnification). The
fibrous structure with multi-axial fiber orientation is shown. The
apparent porosity is suitable for cell and tissue ingrowth. FIG.
3(d) shows a decellularized and lyophilized porcine dermis surface
(60.times. magnification) for comparison. The lack of porosity
reduces the opportunity for cell and tissue ingrowth. FIG. 3(e)
shows a decellularized and lyophilized bovine shoulder fascia
(100.times. magnification) in cross section. The fascial layers and
multi-axial fiber orientation is shown. FIG. 3(f) shows a
decellularized and lyophilized bovine shoulder fascia (250.times.
magnification). The discrete layers of collagen with multi-axial
fiber orientation is shown. FIG. 3(g) shows a decellularized and
lyophilized bovine shoulder collagen surface (light microscope
40.times. and 100.times. magnifications). Hyalinized bands of loose
connective tissue are shown. No cell nuclei are identified by light
microscopy within H & E stained sections.
[0034] In certain embodiments, the biomaterial may have a plurality
of pores, or open spaces between fibers. Typically, the pores or
open spaces may have a variety of sizes ranging from 20 to 300
microns, or from 50 to 200 microns. Certain regions of the
biomaterial may have larger pores, ranging in sizes from 100 to 300
microns that may appear as "open spaces between fibers." The pores
or open spaces may aid in tissue integration thus decreasing
adhesion formation, especially adhesion formation to viscera. The
pores or open spaces may afford tissue ingrowth.
[0035] In certain embodiments, the biomaterial may be cross-linked
or not cross-linked. The biomaterial may be cross-linked by
chemical modification to make it more resistant to tearing,
degradation, creep and attenuation under functional loading. In
certain embodiments, the biomaterial is perforated or formed into a
mesh for improved tissue grafting or integration.
[0036] In certain embodiments, the biomaterial has been processed,
modified or treated to remove cells, fat, protein (e.g.,
non-collagenous protein), nucleic acid, non-collagenous and/or
antigenic components present in the mammalian or non-human source
from which the biomaterial was derived. In certain embodiments, the
biomaterial has been cleaned, decellularized, de-fatted, purified
and/or lyophylized.
[0037] While not intending to be bound by theory, it appears that
layering the biomaterial provides the biomaterial with increased or
additional strength. In certain embodiments, the biomaterial may
include at least 2, 3, 4, or more layers. In certain embodiments,
the biomaterial includes a plurality of biomaterial elements
stitched, sutured, joined or quilted together to increase size or
thickness. Such biomaterials with increased size or thickness may
provide stronger augmentation materials or in larger sizes to fit a
variety of clinical conditions.
[0038] In certain embodiments, the biomaterial may be combined
with, treated with or formed into a multi-component, or coated,
fused or layered construct, with one or more second materials. The
second material may include a material that provides the
biomaterial with increased or additional strength. The second
material may be autologous (i.e., harvested from the recipients'
own body) or may be xenograft to the recipient (i.e., harvested
from a donor, e.g., of the same or different species).
[0039] The second material may comprise a synthetic or biologic
hard, semi-soft or soft, flexible or rigid, mesh, implant, graft,
or prosthesis. The second material may limit, prevent, and retard
adhesion formation, especially adhesion formation to viscera. The
second material may include an absorbable polymer mesh. The second
material may include a polymer material or an absorbable layer.
Exemplary polymer material that can be used in accordance with the
invention includes but not limited to polyglycolide, polydioxanone,
polypropylene (PP), polyester, polytetrafluoroethylene (PTFE),
expanded polytetrafluoroethylene (ePTFE),
polyetheylene-terephthalat (PET), and mixtures thereof. Various
types of absorbable polymer mesh are commercially available
including Vicryl.RTM. mesh (polylgalactin 910) or Monocryl.RTM.
(polyglecaprone 25).
[0040] The second material may include tissues of a mammalian,
human or non-human recipient. The second material may improve or
increase integration, grafting, durability or stability of the
biomaterial when integrated into or combined with tissue of a
mammalian, human or non-human recipient. The second material may
include mammalian cells that are autologous or are a xenograft with
respect to the source of the biomaterial, or are autologous or are
a xenograft with respect to the recipient of the biomaterial. The
mammalian cells includes dermis cells, or stem cells, fibroblasts,
myoblasts, myocytes, endothelial cells, immune cells (macrophages,
monocytes), osteoblasts, or chondroblasts. In certain embodiments,
the biomaterial is a xenograft with respect to a potential
recipient of the material. For example, a human recipient may
receive a non-human biomaterial, for example, from a donor such as
a pig (porcine), cow (bovine), sheep (ovine), horse (equine), and
goat (hircine).
[0041] Second materials also include factors (proteins, hormones,
etc.) that promote blood vessel growth, tissue integration of the
biomaterials. The second material may include an autologous or
recombinant growth factor, chemokine or cytokine, such as platelet
derived growth factor (PDGF), epidermal growth factor (EGF),
insulin like growth factor (IGF)-1, fibroblast growth factor (FGF),
transforming grow factor (TGF), such as TGF-beta. The second
material may include a bone morphogenic protein (BMP), such as
BMP-2, BMP-3, BMP-4, or BMP-7. In certain embodiments, the
biomaterial is treated with autologous or recombinant growth
factors such as PDGF, EGF, IGF-1, FGF, TGF-beta, BMP-2, BMP-3,
BMP-4, BMP-7 or a combination thereof.
[0042] In certain embodiments, second materials include mitogenic
agents such as autologous platelet rich plasma or allogenic
platelet concentrate to enhance cell attachment, migration and
wound healing. Accordingly, a biomaterial may be combined with any
other second material to provide distinct, additional, or
synergistic characteristics, structures or functions.
[0043] In certain embodiments, a biomaterial has a first rough side
and an opposing second dense side. The first rough side may provide
for cell ingrowth in a recipient. Generally, the second dense side
is a more fibrous layer. The second dense side may provide for
reduced cell ingrowth or adhesion to viscera or bowel of a
recipient. The second dense side may include one, two, or more
layers of the same or different materials. For example, the second
dense side may include two or more dense layers for more demanding
applications such as large hernias or abdominal wall
reconstructions. The second dense side may include two or more of
the less dense layers for example as a matrix for stem cell
application in soft tissue repair. Thus, the biomaterial may have a
dual or multi-density construct. In one embodiment, the biomaterial
includes bovine, porcine or equine fascia with a more dense layer
such as a dermis, for example, bovine, porcine or equine
dermis.
[0044] Various techniques can be used to form the multi-layer
construct of the biomaterial including but not limited to welding,
joining, and gluing with an adhesive. Specifically, the layers may
be joined by laser welding, continuous suturing or stitching,
intermittent stitching, or gluing together with cross-linked and
not cross-linked collagen based glue or other biocompatible
adhesives. In certain embodiments, the biomaterial has a quilted,
stitched, sutured, or attached multi-layer construct, a
predominantly flat, folded or rolled sheet. In certain specific
embodiments, the biomaterial is expanded by quilting, stitching,
suturing or attaching together two or more biomaterial elements. In
specific embodiments, two or more flat sheets may be sewn together
with reinforcing rolled borders. The rolled borders serve to
provide a "memory" function so that the biomaterial may be rolled
into a cylinder (e.g., scroll), delivered via trocar and then
spontaneously unrolled itself back into a flat sheet. The rolled
borders may be obtained from the linea alba, or constructed from
other tendinous of an animal such as the Achilles tendon, or rectus
sheath fascia. In certain embodiments, the biomaterial can be cut
or trimmed into a variety of sizes and shapes such as oval,
circular, rectangular or square. The biomaterial can be cut without
loss of fiber integrity or disruption of fiber orientation.
[0045] Certain embodiments of the invention provide a biomaterial
that exhibit physical, structural, physical-chemical,
bio-mechanical, properties suitable for use in accordance with the
invention. Such physical, structural, physical-chemical,
bio-mechanical, properties can be combined.
[0046] For thickness, the biomaterial may have a thickness between
0.2 mm and 5 mm, between 0.4 mm and 2.5 mm, or between 0.8 mm and
2.5 mm. In an exemplary embodiment, mean thickness was about 2.7,
with a range of 2.1 to 3.4 mm. Commercially available hernia repair
material ranges from 1.2 to 2.8 mm, such that the foregoing
biomaterial is suitable for hernia repair and similar
applications.
[0047] For suture retention strength, the biomaterial may exhibit
suture retention strength of greater than 20 Newtons (N), greater
than 50 N, between 4 and 150 N, between 20 and 150 N, or between 20
and 80 N. In an exemplary embodiment, mean suture retention
strength was 49 with a range of 30 to 66. Commercially available
hernia repair material ranges from 29-127N, such that the foregoing
biomaterial is suitable for hernia repair and similar
applications.
[0048] For tear resistance, the biomaterial may exhibit tear
resistance of at least 5 N, between 5 and 100 N, between 10 and 90
N, or between 10 and 50 N. In an exemplary embodiment, mean tear
resistance was 26N with a range of 17 to 38 N. Commercially
available hernia repair material ranges from 17-85 N such that the
foregoing biomaterial is suitable for hernia repair and similar
applications.
[0049] For tensile strength (i.e., uniaxial or multiaxial tensile
strength), the biomaterial may exhibit tensile strength of at least
20 N, or between 50 and 500 N. Alternatively or in addition, a
biomaterial may have between 2 mega pascals (MPa) and 30 MPa of
tensile strength.
[0050] For ball burst tensile strength, the biomaterial may exhibit
a ball burst tensile strength of at least 50 N/cm, between 50 and
1200 N/cm, or between 60 and 1100 N/cm. In an exemplary embodiment,
mean ball burst tensile strength was 188 N/cm with a range of
100-286 N/cm. Commercially available hernia repair available
material ranges from 271 to 1028 N/cm such that the foregoing
biomaterial is suitable for hernia repair and similar
applications.
[0051] For ball burst maximum load, the biomaterial may exhibit
ball burst maximum load of 700 N, with a range of 400 to 1200
N.
[0052] For ball burst strain (a measurement of the percentage of
stretch at a stress of 16N/cm), the biomaterial may exhibit ball
burst strain (stretch) of at least 10%, at least 20%, between 5%
and 35%, between 10% and 30%, or between 10% and 20%. In an
exemplary embodiment, mean ball burst strain (at a stress of
16N/cm) was 15% with a range of 9 to 25%. Commercially available
hernia repair ball burst strain ranges from 10 to 26% such that the
foregoing biomaterial is suitable for hernia repair and similar
applications.
[0053] Typically, the biomaterial exhibits comparable or better
ball burst tensile strength, for exampe, in terms of Maximun Load,
and/or Tensile Strength at Burst and Strain than other collagen
products (see, e.g., Deeken et al., "Differentiation of biologic
scaffold materials through physicomechanical, thermal, and
enzymatic degradation techniques;" Annals of Surgery,
e-publication. Feb. 4, 2012).
[0054] In certain embodiments, a method for manufacture of hernia
implant comprises forming at least two independent structures, one
biologic and one synthetic and joining structures to form a
composite flexible structure.
[0055] The biomaterial include materials that are stable under
conditions used for sterilization, for example, with gamma or
electron beam radiation, and additionally are stable on storage and
in the course of delivery. The biomaterial is usually packaged in a
sterile double package prior to delivery to sterilization.
[0056] In accordance with the invention, methods and uses of repair
or augmentation of a tissue, such as a soft or a hard tissue, are
provided. In certain embodiments, the tissue includes congenitally
attenuated, damaged or injured tissue as a result of deformity,
disease or trauma. In certain embodiments, the repaired or
augmented tissue is abdomen, abdominal wall or muscle.
[0057] In one embodiment, a method and use for repair or
augmentation of a tissue of a recipient mammalian subject in need
of repair or augmentation, includes attaching, joining or affixing
thereto a biomaterial described herein to the tissue of the
recipient mammlian subject in need of repair or augmentation.
[0058] In certain embodiments, a biomaterial for a recipient can be
a xenograft or allograft biomaterial. As used herein, the term
"xenograft," refers to tissue transferred from one subject of one
species to a recipient of another species. As used herein, the term
" allograft," refers to tissue transferred from one subject of one
species to a recipient of the same species ("allogeneic"). With
respect to soft tissue for xenografts, porcine, bovine, ovine,
equine or hircine can be harvested to form xenografts or allografts
according to procedures known to those of ordinary skill in the
art.
[0059] In one embodiment, a method and use for closure or repair of
a wound or cavity in a tissue of a recipient mammlian subject,
includes a) providing a biomaterial described herein; b) contacting
the wound with the biomaterial, or positioning, shaping or
contouring the biomaterial over the cavity, or introducing the
biomaterial into the cavity; c) joining, attaching or affixing the
biomaterial to the wound or cavity to secure said biomaterial; and
d) closing said cavity or repairing said wound in the tissue.
[0060] In one embodiment, a method and use of repairing a defect or
augmenting a tissue of a recipient mammlian subject in need
thereof, includes a) positioning, shaping or contouring the
biomaterial described herein to cover a defect or augment the
tissue in need thereof; and b) securing the biomaterial in
place.
[0061] In one embodiment, a method and use for tissue repair or
augmentation includes delivering to tissue of a recipient mammlian
subject a biomaterial described herein, wherein the biomaterial
serves to repair or augment the tissue. In a further embodiment,
the biomaterial is delivered through small entrances such as
laparoscopic ports, or large incisions to tissue of a recipient
mammlian subject. In a specific embodiment, the biomaterial is
delivered to tissue of a recipient mammlian subject according to a
laparoscopic surgical procedure.
[0062] A saggital view of incarcerated small intestine being
trapped within an abdominal wall defect (hernia defect) is
illustrated in FIG. 4. The incarcerated small intestine is
withdrawn from the hernia defect according to a laparoscopic
surgical procedure. A diagramatic representation of a sagittal view
of a small intestine withdrawn from the abdominal wall defect with
subsequent coverage of the defect utilizing the methods and uses of
the invention is illustrated in FIG. 5. A diagramatic
representation of a post-laparascopic hernia repair view
illustrating the biomaterial has been surgically secured to the
abdominal wall and covering the hernia defect is illustrated in
FIG. 6. The figure also shows the location of the laparascopic
ports.
[0063] Recipient mammalian subjects may be any mammalian species,
such as but not limited to human, dog, cat, horse, pig, and sheep.
The recipient mammlian subject may have an abdominal wall defect,
trauma, damage, or weakness, a hernia, a fistula, or torn or
damaged dura, or an orthopedic defect trauma, damage, or weakness
(e.g., damaged or injured ligament or tendon). In one embodiment,
the recipient mammlian subject is suffering from a hernia, such as
a ventral incisional hernia; a umbilical, inguinal, femoral,
spigelian, parastomal or hiatal hernia; a diaphragmatic hernia; and
a lumbar triangle hernia.
[0064] In certain embodiments, the recipient mammlian subject is in
need of pelvic floor reconstruction; in need of repair,
reinforcement or augmentation of esophageal perforations or
defects; in need of a protective barrier between vascular
anastamosis and bowel; in need of a protective barrier between
viscera following repair; in need of correction or surgery for
rectal prolapse; in need of maxillofacial, periodontal or dental
surgery: as a soft tissue augmentation material or in the repair of
hard and/or soft tissue defects; in need of skeletal defect repair;
in need of orthopedic surgery; in need of urologic surgery; in need
of gynecologic surgery; in need of plastic surgery; or in need of
neurosurgery.
[0065] In certain embodiments, the recipient mammlian subject is in
need of a protective barrier between vascular anastamosis (i.e.,
proximal aortic anastamosis) and bowel (i.e., duodenum) as
encountered following aortic reconstruction utilizing prosthetic
vascular grafts; in need of a protective barrier between viscera
following repair of rectovaginal fistula, rectovesicle fistula; in
need of skeletal defect repair in the craniomaxillofacial or axial
skeleton; in need of orthopedic surgery for joint repair or
replacement or in soft tissue repair or augmentation of joints or
to reinforce, augment, replace weakened, injured, attenuated or
diseased ligamentous, tendinous or joint structures; in need of
urologic surgery for stress urinary incontinence or organ prolapse
(e.g., rectal prolapse); in need of gynecologic surgery to correct
or reinforce for pelvic floor weakness, as in rectocele, cystocele,
vaginal prolapse; in need of plastic surgery to support or
reinforce, inhibit or limit migration of implanted prosthesis,
reinforce or augment defects or areas of weakness created by
mobilization of soft tissues used in various reconstructive
procedures, or to create, alter or manipulate body contours; or in
need of neurosurgery for dural replacement and/or patch of a dural
defect.
[0066] Methods and uses of the invention can be practiced with
respect to all variations of biomaterials set forth herein. For
example, in some embodiments, the biomaterial is a xenograft with
respect to the recipient mammalian subject. In other embodiments,
the biomaterial is an allograft with respect to the recipient
mammalian subject. For example, the biomaterial is a decellularized
and/or lyophyized xenograft or allograft with respect to the
recipient mammalian subject. In certain embodiment, the biomaterial
may further include cells or proteins that are allogeneic or
autologous with respect to the recipient mammalian subject.
[0067] Certain embodiments of the invention provides methods for
manufacturing biomaterials suitable for tissue repair or
augmentation includes (a) obtaining a multi-layered, naturally
occurring multi-axial oriented biomaterial comprising predominately
type I collagen fibers; and (b) processing, modifying or treating
the biomaterial to be suitable as a xenograft in human and
non-human mammal tissue repair or augmentation.
[0068] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
methods and materials similar or equivalent to those described
herein can be used in the practice or testing of the invention,
suitable methods and materials are described herein.
[0069] All applications, publications, patents and other references
cited herein are incorporated by reference in their entirety. In
case of conflict, the specification, including definitions, will
control.
[0070] As used herein, the singular forms "a", "and," and "the"
include plural referents unless the context clearly indicates
otherwise.
[0071] As used herein, numerical values are often presented in a
range format throughout this document. The use of a range format is
merely for convenience and brevity and should not be construed as
an inflexible limitation on the scope of the invention.
Accordingly, the use of a range expressly includes all possible
subranges, all individual numerical values within that range, and
all numerical values or numerical ranges including integers within
such ranges and fractions of the values or the integers within
ranges unless the context clearly indicates otherwise. This
construction applies regardless of the breadth of the range and in
all contexts throughout this document. Thus, for example, reference
to a range of 10-30% includes 10-13%, 11-14%, 12-15%, 13-16%,
10-20%, 11-25%, 15-25%, 20-25%, 25-30%, and so forth. Reference to
a range of 10-30% also includes 11%, 12%, 13%, 14%, 15%, 16%, 17%,
etc., as well as 11.1%, 11.2%, 11.3%, 11.4%, 11.5%, etc., 12.1%,
12.2%, 12.3%, 12.4%, 12.5%, etc., and so forth.
[0072] In addition, reference to a range, for example, of 4-150 N
(e.g., suture retention strength) includes 4, 5, 6, 7, 8, 9, 10, .
. . 146, 147, 148, 149, and 150 as well as 4.1, 4.2, 4.3, 4.4, 4.5,
etc., 5.1, 5.2, 5.3, 5.4, 5.5, etc., 149.1, 149.2, 149.3, 149.4,
149.5, and any numerical range within such a ranges, such as 4-10,
4-50, 10-30, 10-60, 10-140, 80-130, 80-140, 80-150, etc. In a
further example, reference to a range of 4-150 N, includes without
limitation 10-20, 20-30, 30-40, 40-50, 50-60, 60-75, 75-100 N, and
any numerical value or range within or encompassing such
values.
[0073] As also used herein a series of ranges are disclosed
throughout this document. The use of a series of ranges includes
combinations of the upper and lower ranges to provide another
range. This construction applies regardless of the breadth of the
range and in all contexts throughout this document. Thus, for
example, reference to a series of ranges such as between 5% and
35%, between 10% and 30%, and between 10% and 20%, includes ranges
such as 5-30%, 5-35%, 5-20%, 10-35%, 5-10%, and so forth.
[0074] The invention is generally disclosed herein using
affirmative language to describe the numerous embodiments. The
invention also specifically includes embodiments in which
particular subject matter is excluded, in full or in part, such as
substances or materials, method steps and conditions, protocols,
procedures, assays or analysis. Thus, even though the invention is
generally not expressed herein in terms of what the invention does
not include, aspects that are not expressly included in the
invention are nevertheless disclosed herein.
[0075] A number of embodiments of the invention have been
described. Nevertheless, it will be understood that various
modifications may be made without departing from the spirit and
scope of the invention. Accordingly, the following examples are
intended to illustrate but not limit the scope of invention
described in the claims.
EXAMPLES
Example 1
[0076] This example describes a biomaterial suitable for tissue
repair or augmentation.
[0077] A section of porcine abdominal wall was harvested from a
market-size pig in a USDA inspected facility. The animal was
certified for human consumption and further inspected and certified
as such by a veterinarian. The entire abdominal wall was harvested
by means of a wide, full-thickness circular incision from the
costal margins superiorly to the pelvic region inferiorly,
harvesting as much tissue as possible and extending posteriorly to
the spine. No midline incision was made to preserve the integrity
of the rectus sheath. The tissue was transported to an appropriate
facility where it was washed thoroughly using room temperature
water. The skin and superficial fat was removed by mechanical means
using sharp and blunt dissection, and the tissue was washed again
with running deionized water. The tissue was disinfected in 0.5%
sodium hypochlorite solution, and it was frozen for shipping and
storage. Alternatively, to avoid the freezing step, the tissue may
be placed into a solution containing a protease inhibitor and an
antibiotic. Examples of appropriate protease inhibitors includes
ethylenediaminetetracetic acid (EDTA) in concentrations of 1-15 mM
or 0.2 mM phenymethylsulfonyl flouride (PMSF). Examples of
appropriate antibiotics includes solutions such as Penicillin,
Gentamycin or Vancomycin.
[0078] To harvest the fascial layers, the tissue was first allowed
to slowly thaw at 20 to 25.degree. C., and additional cleaning and
dissection was carried out until the fascial layer overlying the
external oblique was visualized. Using blunt and sharp dissection,
the fascial layer (multi-laminar and multi-directional) was
isolated and cleaned, and as much superficial fat was removed as
possible. Dissection was carried out laterally to the medial
borders of the oblique muscles and superiorly and inferiorly to the
borders of the tissue. Once the rectus abdominis muscles were
identified, a small incision was made bilaterally on the lateral
border of the muscle, and the muscle was separated from the fascial
layers anteriorly and posteriorly using a combination of blunt and
sharp dissection such that the muscle was removed in its entirely
from the fascial layers. The fascial tissue was then further
treated to remove fat, non-collagenous proteins, blood vessels and
cells, leaving behind a clean, predominately type I collagen
multilayered membrane.
[0079] To begin the decellularization process, the tissue was
rinsed under running water, and then immersed in a dilute solution
of sodium hypochlorite for 15 minutes. Chemical de-fatting was
carried out by dehydrating the tissue in 100% ethanol for 10
minutes, followed by rotary agitation in a mixture of hexane (70%)
and acteone (30%) for 24 hours. The tissue was rinsed with 100%
ethanol for 10 minutes, and then with 70% ethanol for 10 minutes.
The rinsed tissue was placed in deinonized water for 1 hour. The
water was changed and the tissue was rinsed for an additional two
1-hour cycles using rotary agitation at 200 RPM. Decellularization
was accomplished by placing the tissue in a solution of 1% Triton
X-100 in phosphate buffer with 1% EDTA for 24 hours using rotary
agitation at 200 RPM. After the first 2 hours, the solution was
exchanged for fresh solution, soaked for 4 hours and exchanged
again after 12 hours. The tissue was then washed again in DI water
for three 1-hour cycles. The tissue was then placed in 1% sodium
dodecyl sulphate (SDS) in phosphate buffer for 24 hours using
rotary agitation at 200 RPM. It was then rinsed in DI water, using
three 1-hour cycles and then placed into phosphate buffer for 1
hour. Lyophylization was carried out by placing the wet tissue onto
stainless steel trays and placing into a lab scale freeze dryer.
Lyophylization was initiated by freezing with a shelf temperature
set to -40.degree. C. and the product was held for 120 minutes at a
pressure 300 millitorr (mtorr). The temperature was ramped to
-20.degree. C. and the pressure was decreased to 50 mtorr over 180
minutes. Next, over the next 400 minutes the temperature was ramped
to 15.degree. C. at 50 mtorr and then to 20.degree. C. and 50 mtorr
over the next 1200 minutes. Next, the temperature was increased to
30.degree. C. and held for 30 minutes at which time the cycle was
terminated. The freeze dryer was then vented with room air and the
product was promptly removed from the lyophylizer and sealed in
polyethelyene bags for storage.
Example 2
[0080] This example describes an exemplary biomaterial from bovine
shoulder fascia.
[0081] A section of bovine shoulder fascia was harvested from a
market-size calf in a USDA inspected facility. The animal was
certified for human consumption and further inspected and certified
as such by a veterinarian. The shoulder fascia was harvested by
careful dissection of the thick layer of fascia overlying the
deltoid, trapezius and omo-brachialis region after the skin and
superficial fat are removed. The tissue was disinfected in mild
sodium hypochlorite solution and frozen for shipping and
storage.
[0082] To begin processing, the tissue was slowly thawed and
additional cleaning and dissection of fat and loose connective
tissue was carried out until the distinct fascial layers were
visualized. Using blunt and sharp dissection, this complex
multi-laminar, multi-directional layer was isolated and cleaned,
removing as much superficial fat as possible.
[0083] Next, the tissue was rinsed under running, pyrogen-free
water, then immersed in a dilute solution of 0.5% sodium
hypochlorite. The tissue was then placed into a 1 L jar containing
950 ml of 1% Triton X-100. The jar was placed on a rotary shaker
for 24 hours. The tissue was rinsed DI water using rotary shaking
three times for 30 minutes. The rinsed tissue was placed into a
phosphate buffer solution for 30 minutes, then placed into a
solution of 2% lipase for 8 hours at pH 8.5. The tissue was then
rinsed in deionized water for two 1-hour cycles using rotary
agitation, then placed again into the phosphate buffer for 30
minutes. Additional de-fatting was carried out by placing the
tissue in a 1 L jar of 70% ethanol with rotary agitation at 200 RPM
for 24 hours followed by a 1 hour rinse with deionized water. A
second detergent step was then done using 0.5% SDS in phosphate
buffer at pH 7.5 for 24 hours at 200 RPM. The tissue was again
rinsed in DI water using two 1 hour cycles and then immersed in
phosphate buffer for 30 minutes.
[0084] Lyophylization was carried out in a laboratory scale
freeze-dryer. The product was placed wet on a stainless steel tray
and frozen using an initial shelf temperature was -40.degree. C.
and held at atmospheric pressure for 120 minutes. The temperature
was slowly ramped to 5.degree. C. at a pressure of 100 mtorr over a
period of 400 minutes, then increased to 15.degree. C. and over a
period of 400 minutes at 100 mtorr, then increased to 20.degree. C.
over a period of 400 minutes at 100 mtorr, then increased to
25.degree. C. over 120 minutes at 100 mtorr, then increased to
30.degree. C. over a period of 40 minutes at 100 mtorr. The
lyophylizer was then vented to room air and the cycle was
terminated. The product was promptly removed from the chamber in
sealed in Tyvek bags for storage.
Example 3
[0085] This example describes mechanical testing of an exemplary
Bovine Fascia Biomaterial.
[0086] The physicomechanical properties of a collagen-based
exemplary biomaterial for hernia repair was evaluated using various
means of mechanical testings described below to determine the
suitability for hernia repair application. These tests were
performed as described (Deeken et al., "Differentiation of biologic
scaffold materials through physicomechanical, thermal, and
enzymatic degradation techniques;" Annals of Surgery,
e-publication. Feb. 4, 2012).
[0087] Exemplary scaffolds (biomaterials) were prepared according
to the process described in Example 2 herein. Thickness of the
biomaterial is indicated in FIG. 7.
A. Laser Micrometry
[0088] The thickness of six scaffolds (biomaterials) was measured
using an LK-081 digital laser micrometer and LK-2101 controller
(Keyence, Woodcliff Lake, N.J.). The thickness of each scaffold was
measured nine times (n=9) and was reported as mean.+-.standard
error of the mean (SEM). The results of the laser micrometry test
are shown in FIG. 7.
[0089] Substantial variability was observed both between different
scaffolds of one embodiment of the biomaterial, i.e., acellular
bovine shoulder (ABS), and between different regions within the
same embodiment of the ABS biomaterial.
B. Biomaterial Suture Retention Strength
[0090] Six scaffolds (n=6) measuring 2.5.times.5.1 cm (1.times.2
inches) were prepared. A custom test fixture was utilized in which
the scaffold was loaded with a gauge length of 2.5 cm (1 inch) and
clamped along the upper edge using pneumatic grips set to 60 psi. A
stainless steel wire with a diameter of 0.36 mm was passed through
the scaffold 1.0 cm from the bottom edge. Polypropylene suture
(e.g. size "0" suture) has a diameter of 0.35 mm. Thus, the
diameter of the wire was chosen to replicate this type of suture as
closely as possible. Each scaffold was tested in tension at a rate
of 300 mm/min (12 in/min) until the suture tore out of the
scaffold. The suture retention strength was recorded as the maximum
load sustained by the scaffold in units of Newtons (N) and is
reported as mean.+-.SEM. The results of the suture retention
strength test are shown in FIG. 8.
[0091] All of the scaffolds (biomaterials) individually
demonstrated suture retention strengths exhibit greater than 20N as
suggested for hernia repair applications (de Vries Reilingh et al,
"Autologous tissue repair of large abdominal wall defects," Br J
Surg. 2007 July; 94(7):791-803, and Deeken et al, (2010)
"Physicomechanical evaluation of absorbable and nonabsorbable
barrier composite meshes for laparoscopic ventral hernia repair,"
Surg Endosc 2010; 25:1451-1552). The overall average of all six ABS
scaffolds also demonstrated suture retention strength greater than
the 20N value suggested for hernia repair applications.
C. Biomaterial Tear Resistance
[0092] Tear resistance testing (based on the ASTM specification
#D2261-07a) was performed. Six scaffolds (n=6) were prepared
measuring 2.5.times.7.6 cm (1.times.3 inches). A 2.5 cm (1 inch)
slit was cut from the midline of the 2.5 cm edge of the scaffold
toward the center of the scaffold to form two tabs or "pant legs".
The left tab was clamped in the upper grip using a pneumatic grip
set to 60 psi, and the right tab was clamped in an identical
fashion in the lower grip. Such arrangement yielded a 2.5 cm gauge
length (1 inch). The test was conducted in tension at a rate of 300
mm/min (12 in/min) until the scaffold tore in half. The "tear
strength" was recorded as the maximum load sustained by the
scaffold in units of Newtons (N) and is reported as mean.+-.SEM.
The results of the tear resistance test are shown in FIG. 9.
[0093] All of the exemplary scaffolds (except ABS-1) individually
demonstrated tear resistance strengths greater than the 20N value
suggested for hernia repair applications. The overall average of
five ABS scaffolds (ABS-2 excluded from the analysis) also
demonstrated tear resistance strength greater than the 20N value
suggested for hernia repair applications.
D. Ball Burst
[0094] Six scaffolds (n=6) measuring 7.5.times.7.5 cm (3.times.3
inches) were prepared for burst testing. A custom test fixture was
fabricated based on ASTM specification #D3787-07. Two circular
grooved stainless steel plates were utilized to clamp the scaffold
(biomaterial) to prevent slipping during the test. A 2.5 cm
diameter (1 inch) stainless steel ball was applied in compression
at a rate of 300 mm/min (12 in/min) until it burst through the
scaffold. The ultimate tensile stress and the strain at a stress of
16N/cm (i.e., the extent of stretch) were recorded in units of N/cm
and percent respectively and are reported as mean.+-.SEM. The
results of the ball burst test are shown in FIGS. 10(a) and
(b).
[0095] All of the scaffolds individually demonstrated ball burst
tensile strengths greater than the 50N/cm value suggested for
hernia repair applications. The overall average of five ABS
scaffolds (ABS-3 excluded from the analysis) also demonstrated ball
burst tensile strength greater than the 50N/cm value suggested for
hernia repair applications.
[0096] All of the scaffolds (except ABS-6) individually
demonstrated ball burst strain values in the suggested range of
10-30% for hernia repair applications. The overall average of five
ABS scaffolds (ABS-3 excluded from the analysis) also demonstrated
ball burst strain value in the suggested range of 10-30% for hernia
repair applications.
Example 4
[0097] This example describes exemplary non-limiting applications
of biomaterials of the invention.
[0098] After induction of general anesthesia to a patient, the
abdomen is prepped and draped in sterile fashion. Those of skill in
the art may carry out the procedure either laparoscopically or
through an open approach. A variety of techniques and modifications
of either approach are also intended.
Laparoscopic Approach
[0099] The peritoneal cavity is insufflated with CO.sub.2 and the
appropriate trocars/ports are inserted laterally to gain entrance
into the peritoneal cavity. The anterior abdominal wall is
examined. Any adherent bowel or omentum is dissected free utilizing
sharp dissection or the Harmonic Scalpel, allowing adequate
visualization of the hernia defects. FIG. 11(a) shows an image of a
pre-repair of hernia defect. The appropriate size and shape
biologic mesh is rolled up and introduced into the peritoneal
cavity through one of the trocars/ports. Subsequently, the mesh is
unrolled and appropriately oriented, which is placed against the
anterior abdominal wall in such a fashion that the hernia defect(s)
is/are covered and overlapped by about 3-5 cm. The mesh is secured
to the abdominal with transfascial sutures at "12, 3, 6 and 9
o'clock" positions, or by means of a Gra-nee Needle. The mesh is
then further secured, between the sutures, at approximately 1 cm
intervals, using an endotacking device. FIG. 11(b) shows an image
of a post-repair of hernia defect. The CO.sub.2 is evacuated, the
trocars/ports are removed, trocar/port sites are sutured, and
anesthesia is terminated.
Open Approach
[0100] An incision is made over the hernia defect and carried down
until the abdominal wall fascia is encountered. The hernia sac is
carefully opened, and any incarcerated contents reduced. Adhesions
involving the abdominal wall are divided circumferentially. The
appropriate size and shape mesh is then circumferentially secured
to the peritoneum and posterior aspect (posterior fascia) of the
anterior abdominal wall with a running suture, approximately 3 cm
from the edge of the defect.
* * * * *