NZ730479B2 - Collagen construct and method for producing the collagen construct - Google Patents
Collagen construct and method for producing the collagen construct Download PDFInfo
- Publication number
- NZ730479B2 NZ730479B2 NZ730479A NZ73047915A NZ730479B2 NZ 730479 B2 NZ730479 B2 NZ 730479B2 NZ 730479 A NZ730479 A NZ 730479A NZ 73047915 A NZ73047915 A NZ 73047915A NZ 730479 B2 NZ730479 B2 NZ 730479B2
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- New Zealand
- Prior art keywords
- collagen
- construct
- fibres
- membrane
- strips
- Prior art date
Links
- 102000008186 Collagen Human genes 0.000 title claims abstract description 154
- 108010035532 Collagen Proteins 0.000 title claims abstract description 154
- 229920001436 collagen Polymers 0.000 title claims abstract description 154
- 229960005188 collagen Drugs 0.000 title claims abstract description 154
- 238000004519 manufacturing process Methods 0.000 title description 5
- 239000012528 membrane Substances 0.000 claims abstract description 46
- 210000001264 Anterior Cruciate Ligament Anatomy 0.000 abstract description 29
- 239000002965 rope Substances 0.000 abstract description 29
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- 241000124008 Mammalia Species 0.000 description 3
- 210000001724 Microfibrils Anatomy 0.000 description 3
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- 241000283898 Ovis Species 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0095—Packages or dispensers for prostheses or other implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/08—Muscles; Tendons; Ligaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
Abstract
There is disclosed a collagen construct comprising a plurality of elongate strips, wherein each strip contains a plurality of collagen fibres that are substantially aligned along the length of the respective strips, and the strips are braided or woven together to produce a collagen construct in the form of a rope that can be used for replacing tendons or ligaments, such as cruciate ligaments. Also disclosed is a method for making or producing the collagen construct from a collagen membrane having a plurality of collagen fibres being substantially aligned parallel to each other in a common direction. The membrane is cut along cut lines that are orientated substantially parallel to that common direction, thereby to separate elongate strips from the membrane. The strips are then braided or woven together to form the collagen construct. The application further discloses the use of said construct in repairing tendons and/or ligaments, such as tears in the anterior cruciate ligament (ACL). form of a rope that can be used for replacing tendons or ligaments, such as cruciate ligaments. Also disclosed is a method for making or producing the collagen construct from a collagen membrane having a plurality of collagen fibres being substantially aligned parallel to each other in a common direction. The membrane is cut along cut lines that are orientated substantially parallel to that common direction, thereby to separate elongate strips from the membrane. The strips are then braided or woven together to form the collagen construct. The application further discloses the use of said construct in repairing tendons and/or ligaments, such as tears in the anterior cruciate ligament (ACL).
Description
COLLAGEN CONSTRUCT AND METHOD FOR PRODUCING THE COLLAGEN
CONSTRUCT
FIELD
The present invention relates to a collagen construct and to a method for producing the
collagen construct.
More particularly, the present invention relates to a collagen construct in the form of a
string or rope for use in replacing tendons and ligaments, such as anterior cruciate
ligaments (ACL) which have ruptured.
BACKGROUND
Ligaments are specialized connective soft tissues which connect different organs or
tissues and attach bone to bone. In the latter case, ligaments provide stability to joints by
being flexible enough to allow natural movement of the bones yet also are strong and
inextensible to prevent resistance to applied forces. Tendons connect muscle to bone
and are capable of withstanding tension. In addition, tendons passively modulate forces
during locomotion, providing additional stability with no active work. Their elastic
properties allow tendons to store and recover energy at high efficiency. In tendons and
ligaments, bundles of collagen fibres are embedded in a connecting matrix made of
proteoglycans components. These bundles of collagen fibres provide the load carrying
elements. In tendons, the collagen fibres are arranged in nearly parallel formation, thus
enabling them to withstand high unidirectional loads. In ligaments, the collagen fibres are
arranged in a less parallel formation, thereby enabling them to withstand predominant
tensile stresses in one direction and smaller stresses in other directions.
Every year, hundreds of thousands of people sprain, tear, or rupture ligaments in
particular in the knee, shoulder, and ankle or suffer from injuries to tendons of the upper
and lower extremities, in particular in the shoulder, knee, foot, and ankle. One such
ligament often affected by these types of injuries is the anterior cruciate ligament (ACL) of
the knee. The ACL serves as a primary stabilizer of anterior tibial translation and as a
secondary stabilizer of valgus-varus knee angulation, and is often susceptible to rupture
or tear resulting from a flexion-rotation-valgus force associated with sports injuries and
traffic accidents. Ruptures or tears often result in: severe limitations in mobility; pain and
17450350_1 (GHMatters) P98293.NZ 03/03/2021
discomfort; and an inability to participate in sports and exercise. More than 200,000
people in the U.S. alone tear or rapture their ACL each year, leading to costs of
approximately $3 billion for ACL reconstructive surgery and extensive rehabilitation. It is
widely known that the ACL has poor healing capabilities. Total surgical replacement and
reconstruction are required when the ACL suffers a significant tear or rupture resulting in
joint instability. The most common practice is to reconstruct a torn ACL by substituting the
torn ligament with the patient's own tissue, also known as an autograft. Other options for
substitute ligaments include donor tissues from another organism, also known as
allografts, as well as synthetic grafts.
Surgeons have considered ligament constructs comprising collagen fibres, biodegradable
polymers and composites thereof. When it comes to synthetic grafts the graft material is
sometimes composed of linear arrangements of natural collagen fibres; however, this
arrangement often makes repairing ruptured or lacerated tendons difficult. Also
depending upon the nature of the repair, the tensile strength is not optimal. Accordingly,
there is a continued need for replacement material, especially for ACLs, which has both
the appropriate mechanical strength and also the appropriate physical properties to
enable surgical implantation.
It is to be understood that, if any prior art publication is referred to herein, such reference
does not constitute an admission that the publication forms a part of the common general
knowledge in the art in any country.
SUMMARY
According to a first aspect, there is provided a collagen construct comprising:
a plurality of elongate strips that have been cut from a collagen membrane
comprising numerous collagen fibres, wherein a majority of the fibres are substantially
aligned parallel to each other in a common direction, each strip having a length;
each strip comprising a plurality of collagen fibres that are substantially aligned
along the length of the respective strips;
wherein the strips are amassed together to produce the collagen construct.
At least one of the collagen fibres in each strip may extend continuously along the entire
length of its respective strip.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
At least 50%, alternatively at least 80%, of the collagen fibres in each strip may extend
continuously along the entire length of each respective strip.
In one embodiment each strip may have a thickness of 50 µm to 400 µm. In another
embodiment each strip may have a thickness of 100 µm to 200 µm.
In one embodiment each strip may have a width of 50 µm to 5 mm. In another
embodiment each strip has a width of 1 mm to 3 mm.
The plurality of the strips may be braided, plaited, woven or twisted together to form one
or more collagen ropes.
A plurality of the collagen ropes may be braided, plaited, woven or twisted together to
form one or more collagen cables.
The collagen construct may have a length of 0.5 cm to 50 cm. In one embodiment the
collagen construct may have a length of 2 cm to 20 cm.
The collagen construct may have a cross sectional area of 0.002 mm to 18mm . In one
embodiment the collagen construct may have a cross sectional area of 0.6 mm to 2 mm .
The collagen construct may be able to withstand a tensile load of 650 N without breaking
or suffering any permanent deformation or damage.
The collagen construct may comprise a tendon or ligament prosthesis. In one
embodiment the prosthesis may be an anterior cruciate ligament prosthesis.
According to a second aspect, there is provided a method for producing a collagen
construct comprising the steps of:
a) cutting a non-human mammalian collagen membrane a collagen membrane
comprising numerous collagen fibres, wherein a majority of the fibres are substantially
aligned parallel to each other in a common direction, along cut lines that are orientated
substantially parallel to the common direction, thereby to separate elongate strips from the
membrane; and
b) amassing together the elongate strips to form the collagen construct.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
The method may comprise the step of treating the membrane with acetone and
subsequently drying the membrane, thereby to fix the collagen fibres in their aligned
orientation.
The method may comprise cutting the membrane in a manner so that each strip has a
width sufficient that at least one of the collagen fibres extends continuously along the
entire length of its respective strip.
The step of amassing the strips may comprise braiding, plaiting, weaving, twisting or
winding together a plurality of the collagen strips to produce a collagen rope.
The method may comprise amassing sufficient strips so that the collagen rope has a cross
sectional area of 0.002 mm to 18mm .
The method may comprise amassing sufficient strips together to produce a collagen rope
of a sufficient size for use as an anterior cruciate ligament prosthesis.
A third aspect provides a medical kit for anterior cruciate ligament replacement,
comprising (a) a collagen construct according to the first aspect; and (b) a sterile package
enclosing the collagen construct.
Also disclosed is a collagen construct as described herein, and to a collagen construct
produced by a method as described herein, for use in replacing a tendon or ligament,
such as an anterior cruciate ligament.
Also disclosed is use of a plurality of elongate strips that have been cut from a collagen
membrane in the manufacture of a collagen construct according to the first aspect suitable
for use in a surgical method of repairing an anterior cruciate ligament tear, partial or
complete, the method comprising:
implanting the collagen construct to augment, repair or replace the anterior
cruciate ligament; and
securing the collagen construct in place.
Yet other embodiments of the present disclosure are directed to an implantable collagen
construct in the form of a rope that provides a new and alternative replacement for a
ligament or tendon, such as an anterior cruciate ligament (ACL) that has ruptured.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
In some embodiments, the implantable collagen construct is constructed out of a plurality
of collagen fibres that are braided and/or woven together so that it is able to withstand a
maximum tensile load of 650 N without breaking or suffering any permanent deformation
or damage. In one embodiment the collagen construct has a diameter of ≤ 10mm and a
cross-sectional area of about 75-80 mm .
Further features, advantages and details of the present invention will be appreciated by
those of ordinary skill in the art from a reading of the figures and the detailed description
of the embodiments that follow, such description being merely illustrative of the present
invention.
BRIEF DESCRIPTION OF THE FIGURES
The present invention will now be described, by way of example, with reference to the
accompanying schematic drawings, in which:
Figure 1 shows a collagen scaffold arranged to be cut into elongated strips;
Figure 2 shows a scanning electron microscopy (SEM) image of the collagen
scaffold of Figure 1 at x100 magnification; and
Figure 3 shows a collagen construct in the form of a collagen rope made from the
elongated strips cut from the collagen scaffold of Figure 1.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
The present invention now is described more fully hereinafter with reference to the
accompanying figures, in which embodiments of the invention are shown. This invention
may, however, be embodied in many different forms and should not be construed as
limited to the embodiments set forth herein; rather, these embodiments are provided so
that this disclosure will be thorough and complete, and will fully convey the scope of the
invention to those skilled in the art.
Like numbers refer to like elements throughout. In the figures, the thickness of certain
lines, layers, components, elements or features may be exaggerated for clarity. Broken
lines illustrate optional features or operations unless specified otherwise.
The terminology used herein is for the purpose of describing particular embodiments only
and is not intended to be limiting of the invention. As used herein, the singular forms “a”,
17450350_1 (GHMatters) P98293.NZ 03/03/2021
“an” and “the” are intended to include the plural forms as well, unless the context clearly
indicates otherwise. It will be further understood that the terms “comprises” and/or
“comprising”, when used in this specification, specify the presence of stated features,
integers, steps, operations, elements, and/or components, but do not preclude the
presence or addition of one or more other features, integers, steps, operations, elements,
components, and/or groups thereof. As used herein, the term “and/or” includes any and
all combinations of one or more of the associated listed items. As used herein, phrases
such as “between X and Y” and “between about X and Y” should be interpreted to include
X and Y. As used herein, phrases such as “between about X and Y” mean “between
about X and about Y”. As used herein, phrases such as “from about X to Y” mean “from
about X to about Y”.
Unless otherwise defined, all terms (including 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. It will be further understood that terms, such as those
defined in commonly used dictionaries, should be interpreted as having a meaning that is
consistent with their meaning in the context of the specification and relevant art and
should not be interpreted in an idealized or overly formal sense unless expressly so
defined herein. Well-known functions or constructions may not be described in detail for
brevity and/or clarity.
It will be understood that when an element is referred to as being “on”, “attached” to,
“connected” to, “coupled” with, “contacting”, etc., another element, it can be directly on,
attached to, connected to, coupled with or contacting the other element or intervening
elements may also be present. In contrast, when an element is referred to as being, for
example, “directly on”, “directly attached” to, “directly connected” to, “directly coupled” with
or “directly contacting” another element, there are no intervening elements present. It will
also be appreciated by those of skill in the art that references to a structure or feature that
is disposed “adjacent” another feature may have portions that overlap or underlie the
adjacent feature.
It will be understood that, although the terms first, second, etc. may be used herein to
describe various elements, components, regions, layers and/or sections, these elements,
components, regions, layers and/or sections should not be limited by these terms. These
terms are only used to distinguish one element, component, region, layer or section from
another region, layer or section. Thus, a first element, component, region, layer or section
17450350_1 (GHMatters) P98293.NZ 03/03/2021
discussed below could be termed a second element, component, region, layer or section
without departing from the teachings of the present invention. The sequence of
operations (or steps) is not limited to the order presented in the claims or figures unless
specifically indicated otherwise.
The terms “implant” and “prosthesis” and “construct” are used interchangeably herein to
designate an implantable collagen construct in the form of a collagen rope or string
configured to replace (at least a portion of) a natural tendon or natural ligament of a
mammalian subject (for veterinary or medical (human) applications). The ligament can be
the anterior cruciate ligament. The term “implantable” means the collagen construct can
be inserted, embedded, grafted or otherwise chronically attached or placed on or in a
patient.
The term “collagen construct” as used herein, refers to a material that comprises collagen.
The collagen construct can be in a finished or final form for use or in an unfinished or pre-
final form. The collagen construct can comprise natural collagen, natural collagenous
tissue, synthetic collagen, and/or any combination thereof. The term “synthetic collagen”
as used herein, refers to collagen material that has been formed and chemically and/or
physically altered from its naturally occurring state into an elongate fibre or bundle of
collagen fibres. In one embodiment the collagen material can be obtained from a collagen
membrane produced according to a method as described in . In other
embodiments the collagen can be non-denatured collagen, such as whole or fragmented
native collagen fibres from tendon or skin.
Exemplary collagen constructs include, but are not limited to, collagen fibres and collagen
fibre bundles that are arranged into cords, twisted cords, strips, braids, plaits, weaves,
cables, ligament or tendon prosthesis, and the like. The collagen fibres or fibre bundles
can be spun, twisted, woven, plaited or braided to define a respective spun, twisted,
woven, plaited or braided collagen construct.
Collagen fibres are composed of three polypeptide chains that intertwine to form a right-
handed triple helix. Each collagen polypeptide chain is designated as an α chain and is
rich in glycine, proline and hydroxyproline. There are a number of different α chains and
different combinations of these α chains correspond with different types of collagen. In
some embodiments, the collagen membrane of the present invention comprises type I
collagen. Type I collagen is composed of two α1 chains and one α2 chain.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
In some embodiments, the collagen fibres or bundles are provided from dense connective
tissue isolated from a source. The term “dense connective tissue” as used herein refers
to the matrix comprised primarily of type I collagen fibres or bundles found in the tendons,
ligaments and dermis of all mammals. Dense connective tissue is distinct from “loose
connective tissue”. Loose connective tissue is characterised by loosely arranged fibres
and an abundance of cells and is present, for example, beneath the epithelia that covers
body surfaces and lines internal organs.
In some embodiments, the present invention provides a collagen membrane comprising
greater than 80% type I collagen. In other embodiments, the collagen membrane
comprises at least 85% type I collagen. In still other embodiments the collagen
membrane comprises greater than 90% type I collagen.
Collagen “microfibrils,” “fibrils,” “fibres,” and “natural fibres” refer to naturally-occurring
structures found in a ligament. Microfibrils are about 3.5 to 50 nm in diameter. Fibrils are
about 50 nm to 50 µm in diameter. Natural fibres are above 50 µm in diameter. In some
embodiments, the fibres and/or collagen construct can contain cells, engineered cells,
stem cells, and the like, as well as combinations of the above.
The term “suture” refers to a flexible elongate material that is used to attach the collagen
construct to a target anatomical structure to help hold the collagen construct in location in
a body. The suture may be resorbable or non-resorbable, synthetic or natural. The
suture can be configured to hold the implant in location for at least an initial post-
implantation period of at least about 1 week, but may reside permanently in the body or,
as noted above, may be substantially resorbable over time. The suture can be a single
filament or multi-filament (braided) thread, floss, gut or wire, or combinations thereof that
can be used to hold a portion of an implant against or attached to target structures,
typically to bone and/or tissue. The suture may comprise a resorbable or non-resorbable
biocompatible material. Examples of suture materials include elastomeric materials, such
as polymers, copolymers and/or derivatives thereof, including Vicryl™, as well as other
materials including NITINOL, and combinations thereof. The suture may be used to with a
suture anchor (bone or tissue anchor).
The term “flexible” means that the so-called member can be flexed or bent.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
The terms “braided” and “woven” and derivatives thereof mean to braid and/or
(inter)weave, interlace and/or interlock in any manner, a plurality, typically three or more,
fibres or bundles of fibres together, including manually or automatically weaving, braiding,
knitting and/or knotting and combinations of these or other interlocking or interlaced
constructions.
Referring to Figure 1 there is shown a collagen scaffold 10 comprising a collagen
membrane 12. The membrane 12 is in the form of a substantially flat web or sheet from
which respective elongate strips 14 can be repeatedly cut, either until the entire
membrane 12 is cut into such strips 14 or until sufficient strips 14 are obtained. Such
cutting will normally be done using a laser cutter, but could also be done using
conventional mechanical cutters or scissors.
Although the membrane 12 is shown to be rectangular in shape when seen in plan view, it
will be appreciated that the membrane 12 can be provided in any other geometrical
shapes, for example such as circular, oval, or trapezoidal. The particular shape of the
membrane 12 may be dependent on the source from which the membrane 12 is obtained.
The term “source” as used herein refers to any collagen tissue containing dense
connective tissue in any mammal. In some embodiments, the tissue containing dense
connective tissue is a tendon. A tendon is the tissue which connects muscle to bone in a
mammal. In some embodiments, the collagen-containing tissue may be isolated from any
mammalian animal including, but not limited to a sheep, a cow, a pig or a human. In other
embodiments, the collagen-containing tissue is isolated from a human.
In the exemplary embodiment, the membrane 12 is produced according to a method as
described in .
The membrane 12 comprises a collagen containing tissue segment obtained from a
porcine inner organ lining that was treated to remove all non-collagenous tissue from the
segment. In an initial treatment all the fatty tissue was physically removed from the tissue
segment, whereafter the tissue segment was subjected to chemical treatment to denature
non-collagenous proteins. Subsequently the tissue segment was centrifuged and washed
to remove residual solutions and nucleic acids from the tissue segment. The tissue
segment was stretched on a frame to reduce its cross-sectional thickness, to yield the
membrane 12 having a desired thickness. The thickness of the membrane 12 is selected
dependent on the intended use of the collagen construct, e.g. the requisite diameter of a
17450350_1 (GHMatters) P98293.NZ 03/03/2021
collagen construct to be formed from the membrane 12, such as can be used for replacing
an anterior cruciate ligament (ACL) which has ruptured. In one embodiment the
membrane 12 has a thickness of between 50 µm to 400 µm. In another embodiment the
membrane 12 has a thickness of between 100 µm to 200 µm. In yet a further
embodiment the membrane 12 has a thickness of about 100 µm.
The membrane 12 can be treated with acetone and air-dried while still stretched on the
frame so that the collagen fibres and fibre bundles therein become fixed in their natural
alignment. However, it will be appreciated that other methods for fixing the collagen fibres
in their natural alignment are also possible, such as alkaline-acid treating the
membrane 12. Thereafter the membrane 12 can be compressed and/or rolled to create a
smooth surface on opposed faces of the membrane 12.
Figure 2 shows a scanning electron microscopy (SEM) image (X100) of the
membrane 12. It can be seen that the membrane 12 comprises numerous fibres 16, a
majority of which are substantially aligned with each other in a common direction. Many
of the fibres 16 may be substantially parallel to each other. As can be seen, the alignment
of the fibres 16 results in the membrane 12 having a clear microscopic grain, similar to
what would be found in a sheet of paper. The fibres 16 can branch into smaller fibres or
fibrils, which can recombine with each other or with other fibres 16. Thus the fibres 16
form an interlinked web in the membrane 12. A number of microfibrils and/or fibrils 20
project transversely from the fibres 16, which assist in interlinking the web of the
membrane 12.
When cutting the strips 14 from the membrane 12, the direction or orientation of a cut
line 18 along which the membrane 12 is to be cut is aligned with the microscopic grain, i.e.
aligned with the direction in which the of the fibres 16 are elongated. The cut lines 18 are
represented in Figure 2 by dashed lines. Although the cut lines 18 are shown in Figure 2
being located relatively near to each other, being spaced by only about 250 µm, it will be
appreciated that neighbouring cut lines 18 can be spaced apart to different extents to
produce a strip 14 having a desired width. In one embodiment the strips 14 have a width
of between 50 µm to 5 mm. In another embodiment the strips 14 have a width of
between 1 mm to 3 mm. In yet another embodiment the strips 14 have a width of
about 2 mm. In this way each of the strips 14 will comprise at least some of the fibres 16
running continuously along the entire length of the strip 14. In some embodiments a
selection of the width of the strip 14 and a selection of the alignment of the cut lines 18 is
17450350_1 (GHMatters) P98293.NZ 03/03/2021
made so that at least 50% of the fibres 16 in the strip 14 will run continuously along the
entire length of the strip 14. In another embodiment at least 80% of the fibres 16 in the
strip 14 will run continuously along the entire length thereof. In still a further embodiment
at least 90% of the fibres 16 in the strip 14 will run continuously along the entire length
thereof.
It will be appreciated that in some embodiments the strips 14 can be cut so as to comprise
a single fibre 16.
One or more of the strips 14 are subsequently amassed in a manner to form the collagen
construct. Prior to such amassing, the strips 14 optionally may be rolled along their
length, i.e. parallel to the alignment of the fibres 16, to form columnar or tubular shapes.
Alternatively the strips 14 can be twisted or spun to form an elongated thread. In one
embodiment shown in Figure 3, the strips 14 are braided together to form a collagen
construct in the form of a collagen rope 22. The braid can be a relatively tight braid to
form the collagen rope 22 having a relatively rigid columnar structure. Alternatively, the
braid can be a relatively loose braid with less structural rigidity and thus provided more
flexibility. The selection of a tight braid or loose braid will depend on the target location in
a patient’s body requiring replacement of a tendon or ligament and the requisite
mechanical properties that need to be exhibited. In some embodiments the loose braid or
plait pattern is preferred as it reduces shear forces within the strips 14 caused by abutting
pressure from adjacent strips 14 during flexing or tensioning of the collagen rope 22.
In some embodiments the collagen rope 22 can comprise three or more strips 14 that are
braided together. In other embodiments the collagen rope 22 can comprise three or more
strips 14 that are plaited together. If it is desired to have the resultant collagen construct
that is even thicker than the collagen rope 22, then multiple collagen ropes 22 can be
braided or plaited together to form a collagen cable.
In some embodiments, the collagen rope 22 has a length of between 0.5-50 cm, typically
between about 1-25 cm, and in some embodiments between about 2-20 cm. In some
embodiments the collagen rope 22 can have a cross-sectional area of between
about 0.002-6 mm , typically between about 0.6-2 mm . In some embodiments the
collagen cable can have a cross-sectional area of between about 1-18 mm . In one
embodiment the collagen construct has a diameter of ≤ 10mm and a cross-sectional area
of about 75-80 mm . In some embodiments, the collagen rope 22 or collagen cable is
17450350_1 (GHMatters) P98293.NZ 03/03/2021
able to withstand a maximum tensile load of 650 N without breaking or suffering any
permanent deformation or damage. The term “maximum tensile load” as used herein
refers to the maximum tensile load that the collagen rope can bear. On a Load v
Extension curve this is represented by the peak load on the curve.
The collagen rope 22 can optionally include, e.g., be coated, impregnated and/or
amalgamated with a gel or other material. The coating may be arranged to promote
fibroblasts, and/or comprise one or more of an anti-inflammatory agent, an antibiotic or
other therapeutic agent.
The collagen rope 22 is biocompatible and may be absorbed, resorbed and/or
biodegradeable over time.
The collagen rope 22 can be configured to have similar or greater tensile strength,
stiffness and dynamic flexibility corresponding to natural tendons or ligaments, such as a
natural anterior cruciate ligament (ACL). Embodiments of the present disclosure are
particularly suitable for augmenting, repairing or replacing tendons and ligament,
particularly ACL that may have ruptured. In such cases the collagen rope 22 is
configured, sized and shaped to define an ACL. Optionally, the collagen rope 22 can be
implanted in a patient using one or more of a suture, suture anchor, bone anchor, bone
tunnel and the like. Typically, the collagen rope 22 will be implanted at the site of the
repair and secured in place by any conventional means known to those skilled in the art,
e.g. suturing, suture anchors, bone fixation devices and bone or biodegradable polymer
screws.
The collagen rope 22 can be provided in a medical kit for ACL replacement. The medical
kit comprises an implantable collagen construct as described above and a sterile package
hermetically enclosing the collagen construct therein.
The foregoing is illustrative of the present invention and is not to be construed as limiting
thereof. Although a few exemplary embodiments of this invention have been described,
those skilled in the art will readily appreciate that many modifications are possible in the
exemplary embodiments without materially departing from the novel teachings and
advantages of this invention. Accordingly, all such modifications are intended to be
included within the scope of this invention as defined in the claims. The invention is
defined by the following claims, with equivalents of the claims to be included therein.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
In the claims which follow and in the preceding description of the invention, except where
the context requires otherwise due to express language or necessary implication, the
word “comprise” or variations such as “comprises” or “comprising” is used in an inclusive
sense, i.e. to specify the presence of the stated features but not to preclude the presence
or addition of further features in various embodiments of the invention.
17450350_1 (GHMatters) P98293.NZ 03/03/2021
Claims (8)
1. A collagen construct comprising: a plurality of elongate strips that have been cut from a collagen membrane comprising numerous collagen fibres, wherein a majority of the fibres are 5 substantially aligned parallel to each other in a common direction, each strip having a length; each strip comprising a plurality of collagen fibres that are substantially aligned along the length of the respective strips; wherein the strips are amassed together to produce the collagen construct. 10
2. A collagen construct as claimed in claim 1, wherein at least one of the collagen fibres in each strip extends continuously along the entire length of its respective strip.
3. A collagen construct as claimed in claim 1 or 2, wherein at least 50% of the collagen fibres in each strip extend continuously along the entire length of each respective 15 strip.
4. A collagen construct as claimed in claim 3, wherein at least 80% of the collagen fibres in each strip extend continuously along the entire length of each respective strip.
5. A collagen construct as claimed in any one of the preceding claims, wherein each 20 strip has a thickness of 50 µm to 400 µm.
6. A collagen construct as claimed in claim 5, wherein each strip has a thickness of 100 µm to 200 µm.
7. A collagen construct as claimed in any one of the preceding claims, wherein each strip has a width of 50 µm to 5 mm. 25
8. A collagen construct as claimed in claim 7, wherein each strip has a width of 1 mm to 3 mm. 17450350_1 (GHMatters) P98293.NZ
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2014904065A AU2014904065A0 (en) | 2014-10-10 | ACL Repair II | |
AU2014904065 | 2014-10-10 | ||
PCT/AU2015/000611 WO2016054686A1 (en) | 2014-10-10 | 2015-10-12 | Collagen construct and method for producing the collagen construct |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ730479A NZ730479A (en) | 2021-03-26 |
NZ730479B2 true NZ730479B2 (en) | 2021-06-29 |
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