NZ748139B2 - Devices for articular tissue repair - Google Patents
Devices for articular tissue repair Download PDFInfo
- Publication number
- NZ748139B2 NZ748139B2 NZ748139A NZ74813917A NZ748139B2 NZ 748139 B2 NZ748139 B2 NZ 748139B2 NZ 748139 A NZ748139 A NZ 748139A NZ 74813917 A NZ74813917 A NZ 74813917A NZ 748139 B2 NZ748139 B2 NZ 748139B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- scaffolds
- scaffold
- suture
- ligament
- repair
- Prior art date
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Abstract
Methods and devices for the repair of a torn or injured ligament or tendon are provided. The methods and devices improve problems with reconstruction techniques that may not withstand physiologic forces applied over time, resulting in loss of anterior cruciate ligament function over time. The methods include the use of multiple scaffolds, e.g., beads. The multiple scaffolds may be positioned along a suture or other device such that they are moveable with respect to one another or the injured tissue. s include the use of multiple scaffolds, e.g., beads. The multiple scaffolds may be positioned along a suture or other device such that they are moveable with respect to one another or the injured tissue.
Description
DEVICES FOR ARTICULAR TISSUE REPAIR
RELATED APPLICATIONS
This application claims the benefit under 35 U.S.C. § 119(e) of U.S. ional
application number 62/358,661, filed July 6, 2016, which is incorporated by reference herein
in its entirety.
BACKGROUND OF THE INVENTION
Intra-articular tissues, such as the anterior cruciate ligament (ACL), do not heal after
rupture. In on, the meniscus and the articular cartilage in human joints also often fail to
heal after an injury. Tissues found e of joints heal by forming a fibrin clot, which
connects the ed tissue ends and is subsequently remodeled to form scar, which heals the
tissue. Inside a synovial joint, a fibrin clot either fails to form or is quickly lysed after injury
to the knee, thus preventing joint arthrosis and stiffness after minor injury. Joints contain
synovial fluid which, as part of normal joint activity, naturally prevent clot formation in
joints. This fibrinolytic s results in ure loss of the fibrin clot scaffold and
disruption of the healing process for tissues within the joint or within articular tissues.
The current treatment method for human anterior cruciate ligament repair after
rupture involves removing the ruptured fan-shaped ligament and replacing it with a point-topoint
tendon graft (ACL reconstruction). While this procedure can initially restore gross
stability in most patients, longer -up demonstrates many post-operative patients have
abnormal ural laxity, suggesting the reconstruction may not withstand the physiologic
forces applied over time (Dye, 325 Clin. Orthop. 130-139 (1996)). The loss of anterior
cruciate ligament function has been found to result in early and progressive radiographic
changes consistent with joint deterioration (Hefti et al., 73A(3) J. Bone Joint Surg. 3
(1991)), and over 70% of patients undergoing ACL reconstruction develop osteoarthritis at
only 14 years after injury (von Porat et al., Ann Rheum Dis. 63(3):269-73 (2004)). As
anterior cruciate ligament rupture is most commonly an injury of young athletes in their teens
and twenties, early rthritis in this group has difficult consequences.
In addition, anterior cruciate ligament reconstruction currently requires use of a
tendon graft, harvested either from elsewhere in the t's leg, or from a donor. Placement
of this graft requires the l of a large amount of the torn anterior cruciate ligament, thus
removing the important oceptive nerve fibers which are ant for ligament
function, namely the dynamic stabilization of the knee. Placement of the graft is also
ended to be within the insertion site of the original anterior cruciate ligament, thus
these zones of specialized tissue are also removed to create a tunnel for the graft.
Synthetic replacements for ligaments have also been developed. These e grafts
made of carbon fiber, GoreTex and other synthetic materials. For grafts made of either
natural materials or synthetic materials, the fibers of the graft are oriented such that they are
parallel to the lines of tension in the ligament, that is in the ion of the long axis of the
ligament. These formations allow the construct to support the tensile load during healing.
SUMMARY OF THE INVENTION
It has been discovered herein, in some aspects of the invention, that multiple small
scaffolds, none of which ts from ligament end to ligament end, when surgically placed
can be used effectively to repair injured ligament and tendon tissue. These findings were
quite surprising. There is an expectation in the art that multiple scaffold pieces would not
provide sufficient strength to be able to support the tensile load placed on the healing
ligament or tendon. The finding that two or more discreet scaffolds placed in the area of the
injury could actually augment nt or tendon repair was unexpected.
In some embodiments the scaffolds are designed to be positioned along and optionally
slide along a containment device such as a suture. The containment device may be used to
move the scaffolds into the desired on in the wound site of the ligament or tendon and
to retain them there as a group. For instance, when the containment device is a suture, the
suture may be fixed to bone tissue on either side of the d tissue. For instance in the
repair of an anterior cruciate ligament the suture may be attached to the femur and tibia,
typically at sites outside the attachment sites of the anterior cruciate ligament. For ligaments,
lly one end of the suture would be attached to one bone (for example, the femur) and
the other end would be attached to a different bone (for example, the tibia).
In some aspects the invention is a device for nt or tendon repair comprising a
containment device with multiple ct biodegradable scaffolds positioned on the
containment device. In some ments the containment device is a suture and the
scaffolds are positioned along the length of the suture and are able to slide along the suture.
In other embodiments the scaffolds are beads. The device for ligament or tendon repair may
include, in some embodiments any of: 2-30, 2-50, 2-100, 5-10, 5-20, 5-50, 5-100, 5-200, 10-
, 10-30, 10-40, 10-50, 10-60, 10-70, 10-80, 10-90, 10-100, 15-20, 15-30, 15-50, 15-100,
-30, 0-40, 20-50, 20-100, or 20-200 scaffolds.
In other embodiments, the body provides the containment for the multiple scaffolds.
An example would be the ondylar notch of the distal femur, into which the multiple
scaffolds can be placed to fill or partially fill the notch. In some embodiments, these scaffolds
can be placed through an arthrotomy. In some embodiments, these scaffolds can be placed
arthroscopically.
In other aspects, the invention is a kit. The kit includes any of the above described
devices and instructions for surgical repair of a nt or tendon using the device. The kit
may also include arthroscopic instruments to tate placement of the scaffolds through
small ons.
In some aspects a device for ligament or tendon repair is provided according to the
invention. The device is a set of distinct biodegradable scaffolds, wherein the set of scaffolds
comprises 2-30 lds, and wherein the scaffolds are 1-50 mm in length. In some
embodiments the scaffolds are ssible expandable scaffolds. In other embodiments the
scaffolds are collagen sponges. In yet other ments the collagen sponges comprise type
I soluble collagen and wherein the collagen s are prepared from a solution of
solubilized collagen in a concentration of greater than 5 and less than or equal to 50 mg/ml.
In yet other embodiments the collagen sponges comprise type I soluble collagen and wherein
the collagen sponges are prepared from a solution of solubilized collagen in a tration
of greater than 50 and less than or equal to 500 mg/ml. In some embodiments, the solution
ns calcium.
Each of the scaffolds in the set are the same in some embodiments. In other
embodiments, at least one of the scaffolds in the set is different from the other scaffolds in the
set. In some embodiments the at least one different scaffold has a different size than the other
scaffolds. For instance, the at least one different scaffold may be larger than the other
scaffolds or the at least one different scaffold may be r than the other scaffolds. In
some embodiments the at least one different scaffold has a different shape than the other
lds. In yet other embodiments the at least one different scaffold is shaped as a sphere
(e.g., beads) or a cylinder.
In some embodiments the at least one different scaffold is sed of a different
biodegradable r than the other scaffolds. For instance, the scaffolds may be comprised
of collagen or the scaffolds may be comprised of a non-collagen polymer.
In some embodiments the set of scaffolds have a total surface area that is r than
a single scaffold used to repair a ligament or tendon injury. For example, a ison of one
cylinder having 3000 units of volume, to four smaller ers to deliver the same volume
demonstrates that the four cylinders have almost double the surface area of the original
scaffold. The first cylinder has the following dimensions: 20mm diameter by 30 mm in length
- volume is 3000*pi mm3 (pi*100*30). The four small cylinders have the following
dimensions: Each is 10 mm in diameter and 30 mm in length - volume of each is 750*pi
mm3. The surface area of the first cylinder is 800 *pi and the surface area of each of the four
small cylinders is 350*pi, with the total surface area being 1400*pi.
In yet other aspects the invention is a kit of any of the devices described herein and
r sing one or more containers to house the set of distinct biodegradable
scaffolds, and instructions for surgical repair of a ligament or tendon using the device. In
some embodiments the kit further includes a containment device housed in one or more of the
containers. In some ments the nment device is a suture and the scaffolds are
threaded onto the suture.
A method for ing a ligament or tendon by placing a set of distinct biodegradable
scaffolds positioned on a containment device into a site of an injured ligament or tendon to
repair the ligament or tendon is provided in other aspects of the invention. In some
embodiments the containment device is attached directly or indirectly to a bone on either side
of the injured ligament or tendon. In yet other embodiments the containment device is a
suture having at least two ends. One end of the suture may be attached to a first fixation
device. In some embodiments a second end of the suture is attached to a second fixation
device. In yet other embodiments the first fixation device is fixed to a femur and the second
first fixation device is fixed to a tibia. In yet other embodiments, one end of the suture is
attached to one bone (i.e. the femur) and the second end of the same suture is attached to a
second bone (i.e. the tibia). The attachments of the suture to the two different bones may be
direct or indirect.
A method for rotator cuff tendon repair of an injury by attaching a first fixation device
to a humerus at a location other than an insertion site of the rotator cuff tendon, attaching a
second fixation device to the tendon at a location remote from the injury site, and connecting
a flexible construct to the two fixation devices is provided in other s of the invention.
In some embodiments, the flexible construct is a suture. In some embodiments, the suture is
absorbable and in some embodiments, the suture is nonabsorbable. In some embodiments, the
suture configuration itself is used as the fixation method in the tendon. In some embodiments,
this is a g suture passage.
In some embodiments a scaffold is placed on the flexible construct so that the scaffold
rests between the torn ends of the rotator cuff tendon without mechanically ing the
ld to the rotator cuff tendon. In some embodiments more than one flexible construct is
placed between the first and second fixation devices. In other embodiments more than one
scaffold is loaded onto the le constructs so that the scaffolds rest n the torn ends
of the rotator cuff tendon without mechanically ing the scaffolds to the rotator cuff
tendon or to each other.
In other aspects the invention is a method for anterior te ligament repair of an
injury sing attaching a first fixation device to a femur at a location other than an
insertion site of the ligament, attaching a second fixation device to a tibia at a location remote
from the insertion site of the ligament, and connecting a flexible construct to the two fixation
devices.
A method for anterior cruciate ligament repair of an injury by placing a set of distinct
biodegradable scaffolds into an intra-articular notch to repair an injured ligament is provided
in other aspects of the invention. The scaffolds are not connected to one another, to the
injured ligament or to tissue surrounding the injured ligament.
The invention relates in some aspects to methods and products that facilitate ligament
healing, including healing of the anterior te ligament, without further damaging the
injured anterior cruciate ligament and without use of a tendon graft. Thus, in some aspects the
ion is a device for ing a ruptured anterior cruciate ligament comprising two suture
ends fixed to the femur outside the anterior te ligament attachment site. Two or more
scaffolds are sequentially delivered, one along each suture end, into the intercondylar notch
of the knee. The suture ends are then fixed to the tibia.
In some ments the scaffold is made of protein, such as, for example, a
synthetic, orbable, or a naturally occurring protein. In other embodiments the scaffold
is a lized material. The scaffold may be able. In other embodiments the scaffold
may be a sponge, a gel, a solid, or a semi-solid. The scaffold may be pretreated with a repair
material. Repair materials include but are not limited to gels, liquids, and els.
In some embodiments, more than two suture ends are used. In some embodiments,
more than two lds are used. The multiple scaffolds could be of the same size or of
varying sizes. In some embodiments, sutures are attached to the femoral bone at two
locations. In some embodiments, sutures are attached to the tibial bone at two locations.
A method of ing a ruptured ligament that involves ing s at two
different sites in the intercondylar notch of the femur, sequentially passing two or more
scaffolds into the intercondylar notch and then securing the sutures at two different sites to
the tibia.
A method of repairing a ruptured ligament that involves anchoring sutures at two
different sites in the intercondylar notch of the femur, sequentially passing two or more
scaffolds into the intercondylar notch and then securing the sutures at one site of the tibia. In
some embodiments, the sutures are d to the tibia with the knee in full extension. In
some embodiments, the tension is placed on the sutures prior to fixing them at the second
bone site. In some embodiments, the sutures are fixed to the femur, the scaffolds passed
along the sutures and the sutures tensioned and fixed to the tibia under tension. In the
preferred embodiment, the s are fixed to the femur, scaffolds placed into the notch,
sutures passed through a tibial tunnel, the sutures are tensioned to reduce the knee and then
the sutures are fixed under tension to maintain the reduction of the tibia under the femur.
A method of repairing a ed ligament that involves fixing the sutures at one site
in the intercondylar notch of the femur, sequentially passing two or more scaffolds into the
intercondylar notch and then securing the sutures at two sites to the tibia.
The scaffold in some embodiments is made from a protein. The protein may be
synthetic, bioabsorbable, or a naturally occurring protein. In some embodiments the scaffold
can absorb plasma, blood, or other body fluids.
In other embodiments the scaffold is tubular, semi-tubular, cylindrical, spherical or
square. The scaffold is a sponge or a gel in some embodiments. In other embodiments the
scaffold is a semi-solid or, atively, a solid.
In yet other ments the scaffolds are expandable. They may optionally fill the
repair site. In some embodiments the scaffolds are bigger than the repair site and in other
embodiments the scaffolds partially fill the repair site. The scaffolds may form around the
ligament at the repair site. The scaffolds may be pretreated with a repair material, such as a
gel or a liquid. In some embodiments the repair al is a hydrogel. In other embodiments
the repair material is collagen.
In yet other embodiments the scaffold is compressible. It may optionally fill the repair
site. In some embodiments the scaffold is bigger than the repair site and in other
embodiments the ld partially fills the repair site. The ld may form around the
ligament at the repair site. The scaffold may be pretreated with a repair material, such as a gel
or a liquid. In some embodiments the repair material is a hydrogel. In other embodiments the
repair material is collagen. In other embodiments, the repair material comprises a platelet. In
other embodiments, the repair material comprises whole blood or any of its cellular
components. In other embodiments, the repair material is autologous blood. In other
embodiments, the repair material is composed of white blood cells, red blood cells, platelets
or . In other ments, the repair material is composed of tes, eosinophils,
basophils or neutrophils. In other embodiments, the repair material is ed of
autologous blood which has been treated after removal from the patient to se the
presence of a specific type of white blood cell within the repair material. In one embodiment,
the blood has been treated to se the presence of monocytes in the repair material. In
other embodiments, the patient has been treated prior to surgery to increase the presence of
white blood cells and/or platelets in the circulating blood that is drawn to use for the repair
material.
A method of repairing a ruptured ligament that involves drilling a hole adjacent to the
insertion site of a ruptured ligament and attaching suture to the bone through the hole is
provided in some aspects of the invention. The method es attaching one or more
sutures to the bone using an anchor, staple, screw, button or similar on device.
A method where two or more sutures are fixed to the femur, and one or more
scaffolds are slid along the suture into the intercondylar notch, and the sutures are fixed to the
tibia. In one embodiment, after placement of the sutures and ld and anchoring of the
sutures to femur and tibia, an additional suture is placed into the tibial stump of the torn ACL
and fixed to the femur in addition to the femur-tibia sutures. In another embodiment, after
placement of the sutures and ld and anchoring of the sutures to femur and tibia, an
additional suture is placed into the l stump of the ACL and secured to the tibia. In
another embodiment, all fixation devices are located in the femoral and tibial epiphyses. In
another embodiment, the femoral fixation device is d in the femoral epiphysis and the
tibial fixation device is located in the tibial ysis.
A method where tunnels are drilled in the tibia and femur and a suture placed in the
stump of the torn ACL and passed through the femoral tunnel for a tibial stump suture or
through the tibial tunnel for a femoral stump suture. This may be done before, during or after
placement of a suture anchored to the femoral and tibial bones. After passage of the suture
through the bone , it is fixed to the bone using an anchor, staple, screw, button or other
similar fixation device. In another embodiment, the suture placed in the stump of the ACL is
anchored to the femoral bone for a tibial stump or the tibial bone for a l stump using a
fixation device such as an anchor, staple, screw or button. This may be done before, during or
after placement of a suture anchored to the femoral and tibial bones.
In some embodiments, the fixation device is bioabsorbable, metal, plastic, etc. In
other embodiments, the fixation device is a screw. In certain ments, the fixation
device has a suture attached to it directly or through a hole drilled in the fixation device. In
some embodiments, the suture is a bioabsorbable, synthetic etc. In other embodiments, the
suture is polyglactin 910.
In some embodiments, the scaffold is synthetic, bioabsorbable, or a naturally
occurring protein. In certain embodiments, the scaffold can absorb plasma, blood, or other
body fluids. In other embodiments, the scaffold is tubular, ubular, cylindrical, or
square. In certain embodiments, the scaffold is pretreated with a repair material. In some
embodiments, the repair material is a gel or a liquid. In other ments, the repair
material is hydrogel. In some embodiments, the repair material is collagen.
In some embodiments, the scaffold is a sponge. In certain embodiments, the scaffold is a gel.
In other embodiments, the scaffold is a olid. In some embodiments, the scaffold is a
solid.
In some embodiments, the scaffold is freely moveable on the suture material. The
scaffolds may be connected to each other or te. They may be separated or moved
together during entry into the joint or once in the wound site.
In some embodiments, the scaffolds are in the form of a er, the dimension of
which may range from 1 mm er to 25 mm diameter and the length from 0.1 mm to 100
mm. The preferred embodiment is for the scaffold to range from 4 to 8 mm in diameter and
from 10 to 20 mm in . In other embodiments, the scaffolds are in the form of a sphere.
The radius of the sphere can range from 0.1 mm to 50mm, with the preferred embodiment
having a radius from 2 to 4 mm. Other shapes with a volume ranging from 1ml to 100ml are
also oned.
In some embodiments, the scaffolds are supplied as a device which contains a suture
with the lds already placed along the suture. In other embodiments, the scaffolds are
placed along more than one suture. In the preferred embodiment, the suture is looped through
a fixation device and the beads are placed on the two free ends of the suture. In the preferred
embodiment, the scaffolds are able to freely slide on the suture material.
Each of the limitations of the invention can encompass various embodiments of the
invention. It is, therefore, anticipated that each of the limitations of the invention involving
any one element or combinations of elements can be included in each aspect of the invention.
This invention is not limited in its application to the details of construction and the
arrangement of components set forth in the ing description or illustrated in the
drawings. The invention is capable of other embodiments and of being practiced or of being
carried out in various ways. Also, the phraseology and terminology used herein is for the
purpose of description and should not be ed as ng. The use of "including",
"comprising", or "having", "containing", "involving", and variations thereof herein, is meant
to encompass the items listed thereafter and equivalents thereof as well as additional items.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1: Schematic illustrating a b asic anatomy of the knee showing the distal femur,
proximal tibia and location of the ondylar notch.
Figs. 2A-2B: Schematic illustrating how one suture can be passed through two holes
of a fixation button to provide two suture ends for indirect nt repair. A suture is passed
through one hole of a button and back through a second hole to anchor the suture, leaving two
free suture ends which can exit the bone into the joint at a location distinct from the nt
insertion site. Fig. 2A shows a Button en face. Fig. 2B shows a side view of the button.
Figs. 3A-3D: Schematic illustrating one method of beaded ligament repair with an
indirect method of attaching the suture to the femur and tibia. Fig. 3A shows the button suture
passed thru button and femur drill hole. Fig. 3B shows the f irst scaffold passed along suture
into notch. Fig. 3C shows the second scaffold passed along second suture. Fig. 3D shows
sutures passed thru tibia and secured to tibia over second button.
Figs. 4A-4D: tic illustrating one other method of indirect ligament repair. Fig.
4A shows an anchor to which the suture is attached. The anchor is placed into the bone of the
femur. Fig. 4B shows first scaffold passed along suture. Fig. 4C shows second scaffold
passed along second suture. Fig. 4D shows sutures secured to tibia with button or other
fixation device.
Fig. 5: Schematic illustrating another exemplary method of indirect tissue repair.
First, an anchor with more than two free suture ends is placed in the femur, with care taken
not to have this injure the anterior cruciate ligament insertion sites on the femur or the
ligament itself. The first scaffold is then passed along one of the suture ends and up into the
ondylar notch. The second scaffold is then passed along the second suture up into the
notch. Additional scaffolds are placed along additional sutures. The suture ends are then
brought through a tibial tunnel and secured to the tibia by tying the ends over a button or
using another fixation device.
Fig. 6: Schematic illustrating one other method of indirect nt . First, two
s, each with two free suture ends are placed in the femur, with care taken not to have
these injure the anterior cruciate ligament insertion sites on the femur or the ligament itself.
The first scaffold is then passed along one of the suture ends and up into the intercondylar
notch. The second scaffold is then passed along the second suture up into the notch.
Additional scaffolds are placed along additional sutures. The suture ends are then brought
through a tibial tunnel and secured to the tibia by tying the ends over a button or using
another fixation device. Two or more tibial tunnels or fixation devices may also be used. Two
or more l tunnels or fixation devices may also be used.
Figs. 7A-7K: A set of raphs illustrating the use of an ct repair technique
using a single scaffold and incorporating a stitch in the tibial ACL stump.
Figs. 8A-8D: post-operative MRIs from patients having lds delivered in
multiple pieces in the notch. The patients had evidence of healing of the ACL. In Fig. 8A, the
torn ACL is visualized. Figs. 8B, 8C, and 8D demonstrate the appearance of the g ACL
at 3 , 6 months and 12 months respectively.
Fig. 9: Graph depicting the results of Lachman Testing at 3 months.
Fig. 10: Graph ing the s of hamstring strength at 3 and 6 months.
Figs. 11A-11C: Schematic illustrating an exemplary method for repairing an ACL
using multiple scaffolds. Fig. 11A depicts scaffolds in the form of beads on 2 areas of a
suture threaded between the tibia and femur. Fig. 11B depicts scaffolds in the form of beads
on multiple areas of a suture threaded between one area of a bone and through the injured
ligament into a second area of the bone. Fig. 11C depicts scaffolds in the form of beads on
multiple areas of a suture threaded between one area of the bone and through the injured
ligament into a second area of the bone, where the beads are pulled tightly into the gap
between the bone and injured ligament.
Figs. 12A-12B: tic illustrating a standard ligament replacement scaffold (12A)
and a set of distinct biodegradable scaffolds (12B).
Fig. 13 is a graph depicting the effect of the number of monocytes on strength of
ligament at 6 months in a clinical trial of ACL repair using multiple scaffolds.
Fig. 14 is a graph depicting the effect of the number of basophils on strength of
ligament at 6 months in a clinical trial of ACL repair using multiple lds.
Fig. 15 is a graph depicting the effect of the number of granulocytes on strength of
ligament at 6 months in a clinical trial of ACL repair using multiple lds.
Fig. 16 is a graph depicting eosilophils based on a g voume in a clinical trial of
ACL repair using multiple scaffolds.
DETAILED DESCRIPTION OF THE INVENTION
Aspects of the invention relate to devices and s for repairing an injured
articular tissue. The device is, in some aspects, a set of scaffolds for repair of articular tissue.
Prior to the invention it was believed that a single ld or other repair material was
important for the promotion of healing in the repair of an injured tissue. It was expected that
if repair material were torn or damaged that it would interfere with the healing process
because it would lack the strength to promote the healing and because the exposed surface
area of the al would be greater. It was discovered quite ctedly, that in contrast to
the understanding in the prior art, the use of multiple distinct scaffolds enhances the healing
of a damaged articular tissue.
Thus, the ion in some aspects s to methods for repairing injured lar
tissue using a set of distinct biodegradable scaffolds. A set of distinct scaffolds, as used
herein refers to more than one scaffold. The lds within the set may be identical to one
another or they may have different properties. For instance, one or more of the scaffolds may
have a different size or shape than the other scaffolds in the set. One or more of the scaffolds
may be comprised of a different al or have a different concentration (e.g. tration
of collagen) or may have a different ty or any other property. Each of the scaffolds in
the set may be different from one another. Alternatively, any number of these scaffolds
within the set may be different from one another.
The number of scaffolds within a set may vary. For instance, the set of scaffolds may
be 2-100 scaffolds. The smaller the scaffolds, the larger the number may be. The set may
include for instance, 2-90, 2-80, 2-70, 2-60, 2-50, 2-40, 2-30, 2-20, 2-10, 2-5, 3-90, 3-80, 3-
70, 3-60, 3-50, 3-40, 3-30, 3-20, 3-10, 3-5, 4-90, 4-80, 4-70, 4-60, 4-50, 4-40, 4-30, 4-20, 4-
, 4-5, 5-90, 5-80, 5-70, 5-60, 5-50, 5-40, 5-30, 5-20, 5-10, 5-100, 10-90, 10-80, 10-70, 10-
60, 10-50, 10-40, 10-30, 10-20, 10-100, 15-90, 15-80, 15-70, 15-60, 15-50, 15-40, 15-30, 15-
, 15-100, 20-90, 20-80, 270, 15-60, 15-50, 15-40, 15-30, 15-20, 15-100, 2-200, 3-200, 4-
200, 5-200, 20-200, 100-200, 2-500, 3-500, 4-500, 5-500, 20-500, 100-500, 2-1,000, 3-1,000,
4-1,000, 5-1,100, 20-1,000, 100-1,000 or 500-1,000.
In some embodiments, one or more of the scaffolds may have a different property
such as size or shape, comprised of a different material, comprised of a different
concentration (e.g. concentration of collagen) or comprised of a different porosity than the
other scaffolds in the set. In some embodiments 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90% or 95% of the
lds have a different property than other scaffolds in the set. In other embodiments, the
scaffolds in the set comprise at least 2 different properties. In other ments they
comprise at least 3, 4, 5, 6, 7, 8, 9, or 10 different properties.
In some aspects the device of the invention for the repair of a ed ligament
includes a scaffold which is configured for the repair of a ruptured ligament, a fixation device
and at least one suture. The scaffold allows the subject's body to develop a network of
capillaries, arteries, and veins. Well-vascularized connective tissues heal as a result of
migration of lasts into the ld. A device of the invention es a connection
between a ruptured ligament, or forms around a torn ligament, and promotes the repair of the
ruptured or torn nt while maintaining the integrity and structure of the ligament,
without requiring the placement of damaging sutures into the ligament or damaging the
ligament insertion site with a drill hole in the insertion site of the ACL. Rather, any sutures or
other containment devices used in these embodiments of the invention are attached to
surfaces other than the ligament or the site of attachment of the ligament to the bone.
A containment device, as used herein, refers to any material used to hold the scaffolds
in an area for a period of time. For instance, sutures may be used to thread and hold a scaffold
in place at the site of injury. Alternatively a biodegradable material such as a mesh or bag
may be used to hold the scaffolds in place at the site of injury. In some embodiments the
containment device is a tube or syringe that the scaffolds or powder is in. For instance the
tube may be used to deliver the scaffolds with a plunger placed at the back of the tube.
The device of these embodiments provides a suture and at least one three-dimensional
ld uct for repairing a ruptured or torn anterior cruciate ligament. The scaffold
provides a connection between the ed ends of the ligament and fibers, or forms around
a torn ligament, after injury, and encourages the migration of appropriate healing cells to
form scar and new tissue in the scaffold.
s and s of the ion may be used to treat either intra-articular or
extra-articular injuries in a t. Intra-articular injuries include, but are not limited to,
meniscal tears, ligament tears, tendon tears and cartilage s. Extra-articular injuries
include, but are not limited to, the ligament, tendon or muscle. Thus, the methods of the
invention may be used to treat injuries to the anterior cruciate ligament, the us,
labrum, rotator cuff tendon, glenoid labrum and acetabular labrum, cartilage, and other
tissues exposed to synovial fluid after injury.
An injury may be a torn or ruptured ligament. A torn ligament is one where the
ligament remains connected but has been damaged causing a tear in the ligament. The tear
may be of any length or shape. A ruptured ligament is one where the ligament has been
completely severed providing two separate ends of the ligament. A ruptured ligament may
e two ligament ends of similar or different lengths. The rupture may be such that a
ligament stump is formed at one end.
An example of a repair site (26) of a ruptured anterior cruciate ligament can be seen in
the schematic illustrating a basic anatomy of the knee showing the distal femur, and proximal
tibia depicted in The anterior te ligament (ACL) is one of four strong ligaments
that connects the bones of the knee joint. The function of the ACL is to provide stability to
the knee and minimize stress across the knee joint. It restrains ive d movement
of the lower leg bone, the tibia (6), in on to the thigh bone, the femur (4), and limits the
rotational movements of the knee. An anterior cruciate ligament is ruptured such that it no
longer forms a tion between the femur bone (4) and the tibia bone (6) in the
intercondylar region (8). The resulting ends of the ruptured ACL may be of any length. The
ends may be of a similar length, or one end may be longer in length than the other.
A scaffold of the device of the invention can be any shape that is useful for
implantation into a subject. The scaffold, for instance, can be tubular, semi-tubular,
cylindrical, including either a solid cylinder or a cylinder having hollow cavities, a tube, a flat
sheet rolled into a tube so as to define a hollow cavity, , an amorphous shape which
conforms to that of the repair space, a "Chinese finger trap" design, a trough shape, or square
or a sphere (bead). Other shapes suitable for the scaffold of the device as known to those of
ordinary skill in the art are also contemplated in the ion.
A tic illustrating a basic anatomy of the knee is shown in Fig. 1. Exam ples of
devices and systems useful ing to the invention are depicted in FIGS. 2-6. Exemplary
surgical methods are also shown pictorially in Fig. 7. A suture (12) may be passed through
one hole of a button (14) and back through a second hole to anchor the suture, leaving two
free suture ends which can exit the bone into the joint at a location ct from the ligament
insertion site (Figs. 2A-2B). Fig. 2A shows a Button en face. Fig. 2B shows a side view of
the button.
Figs. 3-6 show examples of surgical methods med with multiple scaffolds. For
instance, Figs. 3A-3D show one method of multiple scaffold ligament repair. First, drill holes
(16) are created in the femur (4) and tibia (6), with care taken not to have these injure the
anterior cruciate ligament ion sites on each bone or the ligament itself. Then a suture
(12) is placed over a button (14) as illustrated in Fig. 2 and the button passed up through the
femoral tunnel and flipped to anchor the two suture ends on the femur. The first scaffold (18)
is then passed along one of the suture ends and up into the intercondylar notch. The second
scaffold (20) is then passed along the second suture up into the notch. The suture ends are
then brought through a tibial tunnel and secured to the tibia by tying the ends over a button or
using another fixation .
Another method of indirect ligament repair is shown in Figs. 4A-4D. First, an anchor
(22) with two free suture ends is placed in the femur, with care taken not to have this injure
the anterior cruciate ligament insertion sites on the femur or the ligament itself. The first
scaffold is then passed along one of the suture ends and up into the ondylar notch. The
second scaffold is then passed along the second suture up into the notch. The suture ends are
then brought through a tibial tunnel and secured to the tibia by tying the ends over a button or
using another on device.
Fig. 5 shows another exemplary method of indirect tissue repair. First, an anchor (22)
with more than two free suture ends is placed in the femur, with care taken not to have this
injure the anterior cruciate ligament insertion sites on the femur or the nt itself. The
first scaffold (18) is then passed along one of the suture ends and up into the intercondylar
notch. The second scaffold (22) is then passed along the second suture up into the notch.
Additional scaffolds are placed along additional sutures. The suture ends are then brought
through a tibial tunnel and secured to the tibia by tying the ends over a button (14) or using
another fixation device.
A method of indirect ligament repair is also shown in Fig. 6. First, two anchors (22),
each with two free suture (12) ends are placed in the femur (4), with care taken not to have
these injure the anterior cruciate ligament insertion sites on the femur or the ligament itself.
The first scaffold is then passed along one of the suture ends and up into the ondylar
notch. The second ld is then passed along the second suture up into the notch.
Additional scaffolds are placed along onal sutures. The suture ends are then brought
through a tibial tunnel and secured to the tibia by tying the ends over a button or using
another fixation device. Two or more tibial tunnels or fixation devices may also be used.
Figs. 11A, 11B and 11C illustrate an exemplary method for repairing an ACL using
multiple scaffolds (24). Scaffolds (24) in the form of beads on 2 areas of a suture threaded
between the tibia and femur is shown in Fig. 11A. The suture (12) is slack while threaded
h the tunnels (16) in femur and tibia. The suture may be pulled tight and secured by
s (22) or other devices. Fig. 11B depicts an alternate embodiment in which scaffolds in
the form of beads (24) on multiple areas of a suture (12) are ed between one area of a
bone (femur or tibia) and through an injured ligament (28) into a second area of the bone or
the other bone. In Fig. 11C lds in the form of beads on a suture are depicted as threaded
tightly between one area of the bone and through the injured ligament such that the scaffolds
fill the gap between the bone and the injured ligament (28).
A representation of various scaffold configurations are depicted in Figs. 12A and 12B.
A rd ligament ement scaffold (18) is shown threaded on a suture (12) in Fig.
12A. A set of distinct biodegradable scaffolds (24) are shown threaded on a suture (12) in
Fig. 12B.
Figs. 7A-7K is a set of photographs illustrating the use of an ct repair technique
using a single scaffold and incorporating a stitch in the tibial ACL stump. The methods can
also be applied to multiple scaffolds, which may, for instance, be threaded along the suture.
Fig. 7A is a photograph g equipment used in the surgical technique. This
includes 2 Endobuttons, 2.4 mm Drill Pin, Endobutton Drill, Tibial Aimer, Suture Passer,
Keith Needle, Mayo Needle, Foot Kit, and Scaffold.
Arthroscopy for meniscal, other pathology may be performed as shown in Fig. 7B. A
medial rthrotomy is performed and whip stitch is placed into tibial stump. In Fig. 7C a
Tibial Tunnel is drilled. A Tibial Pin is placed adjacent to ACL stump using an aiming device
and overdrilled with a reamer that has sufficient diameter to allow for suture passage through
the tunnel. In Fig. 7D a guide pin is placed in l insertion site of ACL and the proximal
cortex is drilled through, followed by overdrilling with a reamer that has sufficient diameter
to allow for button passage through the tunnel . In Fig. 7E, a proximal cortical button is
assembled with s. Vicryl passing loops are placed through outer holes and nonabsorbable
Core sutures are placed through inner holes. The sutures that have been attached
to the ACL tissue are passed thru central holes. In Fig. 7F the cortical button is passed
through l tunnel and engaged on proximal cortex. Vicryl Passing Sutures are put in
outer holes and sutures to ACL whip stitch thru central holes. In Fig. 7G a straight needle is
used to thread scaffold onto the Core Sutures. The free ends of Core sutures were passed
through tibial tunnel. In Fig. 7H a scaffold is passed up into notch along the Core sutures. The
tibial stump is kept anterior to scaffold. Autologous blood (10cc) is added to the scaffold. In
Fig 7I, the knee was extended and the core sutures were pulled down and tied over a second
cortical button. The Tibial stump of ACL remains anterior to scaffold. In Fig. 7J the ACL
stump sutures were pulled proximally to pull the ACL into the scaffold. The s were tied
using an arthroscopic locking knot down onto the proximal femur to secure the ACL in place.
In these examples, a device for repairing a ruptured or torn ligament includes at least
two scaffolds, one suture and two anchors, such that the combination of scaffolds are
configured for repair is shown. A scaffold that is configured for repair is one that is capable
of being ed into an area requiring repair and promotes regeneration of the ligament. A
scaffold of the ion is capable of ion into a repair site and either forming a
connection between the ends of a ruptured ligament, or forming around a torn ligament such
that, in either case, the integrity and structure of the ligament is maintained. Regeneration
offers l advantages over reconstruction, previously used in ligament repair, including
maintenance of the complex insertion sites and fan-shape of the ligament, and preservation of
remaining proprioceptive fibers within the ligament nce.
A scaffold (14) may function either as an ble or biodegradable regulator of cell
function or simply as a delivery vehicle of a supporting ure for cell migration or
synthesis. Numerous matrices made of either natural or synthetic components have been
investigated for use in nt repair and reconstruction. Natural matrices are made from
processed or reconstituted tissue components (such as collagens and GAGs). Because natural
matrices mimic the structures rily responsible for the reciprocal interaction between
cells and their nment, they act as cell regulators with minimal modification, giving the
cells the ability to remodel an implanted material, which is a prerequisite for regeneration.
Synthetic matrices are made predominantly of polymeric als. Synthetic matrices
offer the advantage of a range of carefully defined chemical compositions and structural
arrangements. Some synthetic matrices are not degradable. While the gradable
matrices may aid in repair, non-degradable matrices are not replaced by remodeling and
therefore cannot be used to fully regenerate ligament. It is also undesirable to leave foreign
materials permanently in a joint due to the problems associated with the generation of wear
particles, thus degradable materials are preferred for work in regeneration. Degradable
synthetic scaffolds can be engineered to control the rate of ation.
A scaffold is preferably made of a compressible, resilient material which has some
resistance to degradation by synovial fluid. Synovial fluid as part of normal joint activity,
naturally prevents clot formation. This fibrinolytic process would result in the premature
degradation of the scaffold and t the healing process of the ligament. The al may
be either permanent or biodegradable material, such as polymers and copolymers. The
scaffold can be composed, for example, of collagen fibers, collagen gel, foamed rubber,
natural material, synthetic materials such as rubber, silicone and plastic, ground and
compacted material, perforated material, or a compressible solid material.
A scaffold may be a solid material such that its shape is maintained, or a semi-solid
material e of altering its shape and or size. A scaffold may be made of expandable
material allowing it to contract or expand as required. The al can be capable of
absorbing plasma, blood, other body fluids, liquid, hydrogel, or other material the ld
either comes into contact with or is added to the scaffold.
The three-dimensional shaped implants may have shape memory. The shape memory
allows the implant to be temporarily ed, delivered by a minimally invasive ,
and resume its preformed three-dimensional shape once placed in the vicinity of the articular
The scaffolds may vary in shape and size. Shapes include, but are not limited to,
beads, spheres, cylinders, squares, rectangles, triangles, oids, hemispheres, hemiellipsoids
, domes or similar kinds of shapes. The sizes of the scaffolds vary, and range, for
example, from a width of 0.5 to 50 mm, 0.5 to 30 mm, 0.5 to 20 mm, 1 to 50 mm, 1 to 30
mm, 1 to 10 mm, 2 to 50 mm, 2 to 30 mm, 2 to 10 mm, 5 to 50 mm, 5 to 40 mm, 5 to 30 mm,
5 to 20 mm, 5 to 10 mm, 10 to 100 mm, 10 to 50 mm, 10 to 30 mm, 10 to 10 mm, 10 to 20
mm, 10 to 40 mm, or 10 to 15 mm.
A scaffold material can be protein, lyophilized material, or any other suitable
material. A protein can be tic, bioabsorbable or a naturally ing protein. A protein
includes, but is not limited to, fibrin, hyaluronic acid, elastin, extracellular matrix proteins, or
collagen. A ld material may be plastic or self-assembling peptides. A scaffold material
may incorporate therapeutic proteins including, but not limited to, es, cytokines,
growth factors, clotting factors, anti-protease proteins (e.g., alpha1-antitrypsin), angiogenic
proteins (e.g., vascular endothelial growth factor, fibroblast growth factors), giogenic
ns (e.g., endostatin, angiostatin), and other proteins that are present in the blood, bone
morphogenic proteins (BMPs), nductive factor (IFO), fibronectin (FN), elial cell
growth factor (ECGF), cementum attachment extracts (CAE), ketanserin, human growth
hormone (HGH), animal growth hormones, epidermal growth factor (EGF), interleukin-1
(IL-1), human alpha thrombin, orming growth factor (TGF-beta), insulin-like growth
factor (IGF-1), platelet derived growth factors , fibroblast growth factors (FGF,
bFGF, etc.), and periodontal nt chemotactic factor (PDLGF), for therapeutic purposes.
A lyophilized material is one that is capable of swelling when liquid, gel or other fluid is
added or comes into contact with it.
Many biological materials are available for making the scaffold, including collagen
compositions (either collagen fiber or collagen gel), compositions containing
glycosaminoglycan (GAG), hyaluran compositions, and various synthetic compositions.
Collagen-glycosaminoglycan (CG) copolymers have been used successfully in the
ration of dermis and peripheral nerve. Porous natural polymers, fabricated as spongelike
and fibrous scaffolds, have been investigated as implants to facilitate regeneration of
selected oskeletal tissues including ligaments. A scaffold, such as a sponge scaffold,
may also be made from tendon (xenograft, allograft, autograft) or ligament or skin or other
connective tissue which could be in the native state or processed to facilitate cell ingrowth or
other biologic features.
In aspects of the invention, a scaffold is composed of a sponge or sponge-like
material. A sponge scaffold may be absorbable or nonabsorbable. A sponge scaffold may be
collagen, elastin, extracellular matrix protein, plastic, or ssembling peptides. A sponge
scaffold may be hydrophillic. A sponge scaffold is e of compression and expansion as
desired. For example, a sponge scaffold may be compressed prior to or during implantation
into a repair site. A compressed sponge scaffold allows for the sponge scaffold to expand
within the repair site. A sponge may be lyophilized and/or compressed when placed in the
repair site and expanded once in place. The expansion of a sponge scaffold may occur after
contact with blood or other fluid in the repair site or added to the repair site. A sponge
scaffold may be porous. A sponge scaffold may be saturated or coated with a liquid, gel, or
hydrogel repair material prior to implantation into a repair site. Coating or saturation of a
sponge scaffold may ease implantation into a relatively undefined defect area as well as help
to fill a ularly large defect area. A sponge scaffold may be composed of collagen. In a
preferred ment, a sponge scaffold is treated with hydrogel.
An important subset of l matrices are those made predominantly from en,
the main structural component in ligament. Collagen can be of the soluble or the insoluble
type. Preferably, the collagen is soluble, e.g., acidic or basic. For example, the collagen can
be type I, II, III, IV, V, IX or X. Preferably the collagen is type I. More preferably the
collagen is soluble type I collagen. Type I collagen is the predominant component of the
extracellular matrix for the human anterior cruciate ligament and es an example of a
choice for the basis of a bioengineered scaffold. Collagen occurs predominantly in a fibrous
form, allowing design of materials with very different mechanical properties by altering the
volume fraction, fiber orientation, and degree of cross-linking of the en. The biologic
properties of cell infiltration rate and ld degradation may also be altered by varying the
pore size, degree of cross-linking, and the use of additional proteins, such as
glycosaminoglycans, growth factors, and cytokines. In addition, en-based biomaterials
can be manufactured from a patient's own skin, thus minimizing the antigenicity of the
implant (Ford et al., 105 Laryngoscope 8 (1995)).
The collagen is synthetic or naturally derived. Natural sources of en may be
obtained from animal or human sources. For instance, it may be d from rat, pig, cow, or
human tissue or tissue from any other species. Tendons, ligaments, muscle, fascia, skin,
cartilage, tail, or any source of collagenous tissue are useful. The material is then implanted
into a subject of the same or different species. The terms “xenogeneic” and “xenograft” refer
to cells or tissue which originates with or is derived from a species other than that of the
recipient. Alternatively the collagen may be obtained from autologous cells. For instance, the
en may be derived from a t’s fibroblasts which have been cultured. The collagen
may then be used in that patient or other patients. The terms “autologous” and “autograft”
refer to tissue or cells which originate with or are derived from the recipient, whereas the
terms “allogeneic” and “allograft” refer to cells and tissue which originate with or are derived
from a donor of the same species as the recipient. The collagen may be isolated any time
before surgery.
The solubilized collagen may be in a tration of 1-50 mg/ml in the solution. In
some embodiments that concentration of solubilized collagen is greater than 5 mg/ml and less
than or equal to 50 mg/ml. In some embodiments that concentration of solubilized collagen is
greater than 50 mg/ml and less than or equal to 500 mg/ml. The concentration of collagen
may be, for instance, 10, 15, 20, 25, 30, 35, or 40 mg/ml. Such high concentrations of
collagen are useful for producing viscosity levels that are desirable for the methods of the
invention. Most commercially available collagen solutions are of lower concentrations.
Higher concentrations can be made, for instance, using the methods bed herein. In other
embodiments the solubilized collagen solution has a tration of 1mg/ml to less than 5
mg/ml. When such lower trations of en are used, onal components or steps
are taken to increase the viscosity of the material in order to be useful according to the
methods of the invention. Examples of viscosity inducing methods or components are
described herein.
The solution should be prepared, by varying the collagen content and other
components, to provide the desired flow properties of the finished composition. In some
embodiments the solution has a collagen viscosity of 1,000 to 200,000 centipoise.
The collagen solution is e for in vivo use. The solution may be sterilized and/or
components of the solution may be isolated under sterile conditions using sterile techniques
to produce a sterile composition. The final desired properties of the composition may be
determinative of how the solution is sterilized because some sterilization techniques may
affect properties such as viscosity. If certain ents of the solution are not to be
ized, i.e., the collagen isolated from natural sources, the remaining components can be
combined and sterilized before on of the collagen, or each component can be sterilized
separately. The solution can then be made by mixing each of the sterilized components with
the collagen that has been isolated using sterile techniques under sterile conditions.
Sterilization may be lished, for instance, by autoclaving at atures on the order
of about 115°C to 130°C, ably about 120°C to 125°C for about 30 s to 1 hour.
Gamma radiation is another method for sterilizing components. Filtration is also possible, as
is sterilization with ethylene oxide.
In some embodiments the scaffold is hydrophilic. The hydrophilicity of the scaffold
can be assessed, for instance, by the ability of the scaffold to absorb an amount greater than
its weight in liquid such as water or blood. In some embodiments the ld has a
hydrophilicity such that it can absorb at least 2X its weight in blood or other fluid. In other
embodiments it can absorb at least 5X, at least 10x, or at least 15X its weight in blood or
other fluid. For ce the scaffolds described in the examples absorbs 5X its weight. At
least 5ml of blood or other repair material is added to the 1g scaffold described in Example 2.
The lized collagen solution may contain additional components, such as
ble collagen, other extracellular matrix proteins (ECM), such as proteoglycans and
glycosaminoglycans, fibronectin, laminin, entectin, decorin, lysyl oxidase, crosslinking
precursors (reducible and non-reducible), elastin, elastin crosslink precursors, cell
components such as, cell membrane proteins, mitochondrial proteins, nuclear proteins,
cytosomal ns, and cell surface receptors, growth Factors, such as, PDGF, TGF, EGF,
and VEGF, and hydroxyproline. In some embodiments hydroxyproline may be present in the
solution in a concentration of 1 to 3.0 μg/ml, which may be 8 to 9% of the total protein in the
collagen solution. In some embodiments, the hydroxyproline is present in a concentration of
0.5 to 4.0 μg/ml in the collagen solution prior to the addition of any buffer. In some
embodiments the collagen on is free of in. “Free of thrombin” as used herein
refers to a composition which has less than 1% thrombin. In some embodiments, free of
thrombin refers to undetectable levels. In other embodiments it refers to 0% thrombin.
A device of the invention may also include one or more fixation devices. An anchor is
a device capable of insertion into a bone such that it forms a stable attachment to the bone. In
some ces the fixation device is capable of being removed from the bone if desired.
Fixation devices include but are not limited to anchors, s (12), buttons (14), or a knot
(tying the suture over a bony bridge). An anchor may be l shaped having a sharpened
tip at one end and a body having a longitudinal axis. The body of an anchor may increase in
diameter along its longitudinal axis. The body of an anchor may include grooves suitable for
screwing the anchor into on. For example, the anchor may be screwed into the femur
bone. An anchor may include an eyelet at the base of the anchor body through which one or
more sutures may be passed. The eyelet may be oval or round and may be of any size le
to allow one or more s to pass through and be held within the eyelet.
A fixation device may be attached to a bone by physical or mechanical methods as
known to those of ry skill in the art. An anchor includes, but is not limited to, a screw,
a barb, a helical anchor, a staple, a clip, a snap, a rivet, or a crimp-type anchor. The body of
an anchor may be varied in length. Examples of anchors, include but are not limited to, INFAST
TM Bone Screw System (Influence, Inc., San Francisco, Calif.), IN-TAC TM Bone
Anchor System (Influence, Inc., San Francisco, Calif.), Model 3000 AXYALOOP TM
Titanium Bone Anchor (Axya Medical Inc., Beverly, Mass.), OPUS MAGNUM®Anchor
with Inserter (Opus Medical, Inc., San Juan Capistrano, Calif.), ANCHRON TM, HEXALON
TM TRINION TM (all available from Inion Inc., ma City, Okla.) and TwinFix AB
absorbable suture anchor (Smith & Nephew, Inc., Andover, Mass.). Anchors are available
commercially from manufacturers such as Influence, Inc., San Francisco, Calif., Axya
Medical Inc., y, Mass., Opus Medical, Inc., San Juan Capistrano, Calif., Inion Inc.,
Oklahoma City, Okla., Arthrex (Naples FL), and Smith & Nephew, Inc., Andover, Mass.
The fixation device may be composed of a non-degradable material, such as metal, for
example um 316 LVM stainless steel, CoCrMo alloy, or l alloy, or plastic. The
bony fixation device is preferably bioabsorbable such that the subject is capable of breaking
down the anchor and absorbing it. Examples of bioabsorbable material include, but are not
limited to, MONOCRYL (poliglecaprone 25), PDS II (polydioxanone), surgical gut suture
(SGS), gut, coated VICRYL (polyglactin 910, polyglactin 910 braided), human autograft
tendon material, collagen fiber, POLYSORB, -lactic acid (PLLA), polylactic acid
(PLA), polysulfone, polylactides (Pla), racemic form of polylactide (D,L-Pla), poly(L-lactideco-D
,L-lactide), 70/30 -lactide-co-D,L-lactide), ycolides (PGa), polyglycolic
acid (PGA), polycaprolactone (PCL), polydioxanone (PDS), polyhydroxyacids, and
able plate material (see e.g. Orthopedics, October 2002, Vol. 25, No. 10/Supp.). The
anchor may be bioabsorbed over a period of time which includes, but is not limited to, days,
weeks, months or years.
A suture (12) is preferably bioabsorbable, such that the t is capable of ng
down the suture and absorbing it, and synthetic such that the suture may not be from a natural
source. A suture (12) may be permanent such that the subject is not capable of breaking down
the suture and the suture remains in the subject. A suture (12) may be rigid or stiff, or may be
stretchy or le. A suture (12) may be round in shape and may have a flat cross n.
Examples of sutures include, but are not limited to, VICRYLTM polyglactin 910,
PANACRYL TM absorbable suture, ETHIBOND®EXCEL polyester suture, PDS®
polydioxanone suture and PROLENE®polypropylene suture. Sutures are available
commercially from manufacturers such as MITEK PRODUCTS division of ETHICON, INC.
of Westwood, Mass. The suture may be as long as the ACL or longer. In an ment, the
suture length is more than 30" in length. In some embodiments, the suture is long enough to
be d over and for both ends to be able to traverse the femur and tibia, with sufficient
extra length to allow for the suture to have a loop outside the knee where the scaffolds are
maintained until the suture is pulled tight (Se FIGs. 3-6, for instance).
A staple is a type of anchor having two arms that are capable of insertion into a bone.
In some instances, the arms of the staple fold in on themselves when ed to a bone or in
some instances when ed to other tissue. A staple may be composed of metal, for
example titanium or stainless steel, plastic, or any biodegradable material. A staple es
but is not limited to linear staples, ar staples, curved staples or straight staples. Staples
are available commercially from manufacturers such as Johnson & Johnson Health Care
Systems, Inc. Piscataway, N.J., and Ethicon, Inc., Somerville, N.J. A staple may be attached
using any staple device known to those of ry skill in the art, for example, a hammer
and staple setter (staple holder). In some embodiments, a staple may be used to hold the
suture securely in position.
A repair site (26) is the area around a ruptured or torn ligament (2) into which a
device of the invention may be inserted. A device of the invention may be placed into a repair
site (26) area during surgery using ques known to those of ordinary skill in the art. A
scaffold (14) of the invention can either fill the repair site (26) or partially fill the repair site
(26). A scaffold (18) can partially fill the repair site (26) when inserted and expand to fill the
repair site (26) in the presence of blood, plasma or other fluids either present within the repair
site (26) or added into the repair site (26).
A scaffold of the device can be pretreated with a repair material prior to implantation
into a subject. The scaffold may be soaked in a repair material prior to or during implantation
into a repair site. The repair material may be injected directly into the ld prior to or
during implantation. The repair material may be injected within a tubular scaffold at the time
of repair. Repair material includes, but is not d to, a gel, for example a hydrogel, a
liquid, or collagen. A liquid includes any material capable of forming an aqueous material, a
suspension or a solution. A repair material may include additional materials, such as growth
factors, antibiotics, insoluble or soluble en (in fibrous, gel, sponge or bead form), a
cross-linking agent, thrombin, stem cells, a genetically d fibroblast, platelets, water,
, extracellular proteins and a cell media supplement. The additional repair materials
may be added to affect cell proliferation, ellular matrix production, consistency,
inhibition of disease or infection, tonicity, cell nutrients until nutritional pathways are
, and pH of the repair material. All or a portion of these additional materials may be
mixed with the repair material before or during implantation, or atively, the additional
materials may be implanted proximate to the defect area after the repair material is in place.
In certain embodiments, a repair material may include collagen and one or more blood
cells, i.e. white blood cells (WBC), platelets, or whole blood). In some embodiments, WBC,
platelets, or whole blood are derived from the subject to be treated. In other embodiments,
WBC, platelets, or whole blood are derived from a donor that is allogeneic to the subject. In
certain embodiments, WBC, platelets, or whole blood may be obtained as platelet rich plasma
(PRP). In a non-limiting example, WBC, platelets, or whole blood may be isolated from a
t's blood using techniques known to those of ordinary skill in the art. As an example, a
blood sample may be centrifuged at 700 rpm for 20 minutes and the platelet-rich plasma
upper layer removed. Platelet density may be ined using a cell count as known to those
of ordinary skill in the art. WBCs or whole blood may be ed using similar techniques
known to the skilled n. The platelet rich plasma may be mixed with collagen and used
as a scaffold. The platelet rich plasma may be mixed with any one or more of the ld
materials of the invention.
In other embodiments, the repair material is autologous blood. In other ments,
the repair material is composed of white blood cells, red blood cells, platelets or plasma. In
other embodiments, the repair material is composed of monocytes, eosinophils, basophils or
neutrophils. In other embodiments, the repair material is composed of autologous blood
which has been treated after l from the patient to increase the presence of a specific
type of white blood cell within the repair material. In one embodiment, the blood has been
treated to increase the presence of monocytes in the repair material. In other embodiments,
the patient has been treated prior to surgery to increase the presence of white blood cells
and/or platelets in the circulating blood that is drawn to use for the repair material.
An example of a gel is a el. A hydrogel is a substance that is formed when an
organic polymer (natural or synthetic) is crosslinked via covalent, ionic, or hydrogen bonds to
create a three-dimensional open-lattice structure which entraps water molecules to form a gel.
A polymer may be crosslinked to form a hydrogel either before or after implantation into a
subject. For instance, a el may be formed in situ, for example, at a repair site. In
certain embodiments, a polymer forms a hydrogel within the repair site upon contact with a
crosslinking agent. Naturally occurring and synthetic el g rs, polymer
mixtures and copolymers may be utilized as hydrogel precursors. See for example, U.S. Pat.
No. 5,709,854. In certain embodiments, a hydrogel is a gel and begins setting immediately
upon e and takes imately 5 minutes to sufficiently set before closure of the
defect and surgery area. Setting time may vary depending on the mixture of gel used and
environmental factors.
For instance, certain polymers that can form ionic hydrogels which are malleable may
be used to form the el. For example, a hydrogel can be produced by linking the
anionic salt of alginic acid, a carbohydrate r isolated from seaweed, with calcium
cations, whose strength increases with either increasing concentrations of calcium ions or
alginate. ed te derivatives, for example, which have an improved ability to form
hydrogels or which are derivatized with hydrophobic, water-labile , e.g., oligomers of
.epsilon.-caprolactone, may be synthesized. Additionally, polysaccharides which gel by
exposure to monovalent cations, including bacterial polysaccharides, such as gellan gum, and
plant ccharides, such as carrageenans, may be crosslinked to form a hydrogel.
Additional examples of materials which can be used to form a hydrogel include
polyphosphazines and polyacrylates, which are crosslinked ionically, or block copolymers
such as PLURONICS TM (polyoxyalkylene ether) or TETRONICS TM (nonionic polymerized
alkylene oxide), polyethylene oxide-polypropylene glycol block copolymers which are
crosslinked by ature or pH, respectively. Other materials include proteins such as
fibrin, polymers such as nylpyrrolidone, hyaluronic acid and collagen. Polymers such
as polysaccharides that are very viscous liquids or are thixotropic, and form a gel over time
by the slow evolution of structure, are also useful.
Another example of a gel is hyaluronic acid. Hyaluronic acid, which forms an
injectable gel with a consistency like a hair gel, may be utilized. Modified hyaluronic acid
derivatives are ularly useful. Hyaluronic acid is a linear polysaccharide. Many of its
biological effects are a consequence of its ability to bind water, in that up to 500 ml of water
may associate with 1 gram of hyaluronic acid. Esterification of hyaluronic acid with
uncharged organic moieties reduces the s solubility. Complete esterification with
organic alcohols such as benzyl renders the hyaluronic acid derivatives virtually insoluble in
water, these compounds then being soluble only in n aprotic solvents. When films of
hyaluronic acid are made, the films essentially are gels which hydrate and expand in the
presence of water.
A gel may be provided in pharmaceutical acceptable carriers known to those skilled in
the art, such as saline or phosphate buffered saline. Such carriers may routinely contain
pharmaceutically acceptable concentrations of salt, buffering agents, vatives,
ible carriers, supplementary immune iating agents such as nts and
cytokines and optionally other therapeutic agents.
As used herein, the term “pharmaceutically acceptable” means a non-toxic material
that does not interfere with the effectiveness of the biological activity of the scaffold material
or repair al. The term “physiologically acceptable” refers to a non-toxic material that is
compatible with a biological system such as a cell, cell culture, tissue, or organism. The
characteristics of the carrier will depend on the route of stration. Physiologically and
pharmaceutically able carriers include diluents, s, salts, buffers, stabilizers,
solubilizers, and other materials which are well known in the art. The term "carrier" denotes
an organic or inorganic ingredient, natural or synthetic, with which the scaffold material is
ed to facilitate the application. The components of the pharmaceutical compositions
also are capable of being co-mingled with the device of the present invention, and with each
other, in a manner such that there is no interaction which would substantially impair the
desired pharmaceutical efficacy.
The devices of the invention may be used in surgical ures. The following is an
example of a surgical procedure which may be performed using the devices and methods of
the invention. The affected extremity is prepared and draped in the standard sterile fashion. A
tourniquet may be used if indicated. Standard arthroscopy equipment may be used. After
diagnostic arthroscopy is performed, and the intra-articular lesion fied and defined, two
sutures are fixed to the femur at a location in the intercondylar notch which is not in the
native insertion site of the anterior cruciate ligament. The torn anterior cruciate ligament
tissue is left in situ and not damaged by drilling though it or placing suture into it. Two or
more scaffolds are then sequentially introduced, into the ondylar notch. The sutures are
then both anchored to the tibia to stabilize the knee and hold the two scaffolds in the vicinity
of the torn ACL. The arthroscopic portals can be closed and a sterile ng placed. The
post-operative rehabilitation is dependent on the joint ed, the type and size of lesion
treated, and the tissue involved.
The device of the invention may be used with arthroscopic equipment. The device of
the invention may be used by ion through an open incision. The scaffold is
compressible to allow uction h arthroscopic portals, ons and equipment.
The scaffold can also be pre-treated in antibiotic solution prior to implantation.
A subject includes, but is not limited to, any mammal, such as human, non-human
primate, mouse, rat, dog, cat, horse or cow. In certain embodiments, a subject is a human.
The invention also includes in some aspects kits for repair of ruptured or torn articular
tissue such as ligaments. A kit may include more than one lds of the invention and
optionally, one or more sutures and bony fixation devices for the femur and tibia. One or
more bone on devices may be attached to the suture or sutures in the kit. A kit may
further include a container that contains a repair material as described herein.
The kit may include one or more containers housing the components of the invention
and/or for collecting or storing blood or cells and instructions for use. The kit may be
designed to facilitate use of the methods bed herein by surgeons and can take many
forms. Each of the compositions of the kit, where applicable, may be provided in liquid form
(e.g., in solution), or in solid form, (e.g., a dry powder). In n cases, some of the
compositions may be constitutable or otherwise processable (e.g., to an active form), for
example, by the addition of a suitable solvent or other species (for example, water or a cell
culture medium), which may or may not be provided with the kit. As used herein,
uctions” can define a component of instruction and/or promotion, and typically involve
written instructions on or associated with packaging of the invention. Instructions also can
e any oral or electronic instructions provided in any manner such that a user will
clearly recognize that the instructions are to be associated with the kit, for example,
audiovisual (e.g., videotape, DVD, etc.), Internet, and/or web-based communications, etc.
The written instructions may be in a form prescribed by a governmental agency regulating the
cture, use or sale of pharmaceuticals or biological products, which instructions can
also reflects approval by the agency of manufacture, use or sale for human administration.
The kit may contain any one or more of the components described herein in one or
more containers. As an example, in one embodiment, the kit may include a container housing
collagen. The collagen may be in the form of a liquid, gel or solid (powder). The collagen
may be ed sterilely and may be packaged and d in the form of le scaffolds.
Alternatively it may be shipped as a single scaffold that can be separated into le
scaffolds prior to or at the time of use. A second container may have buffer solution premixed
prepared ely or in the form of salts. Alternatively the kit may include one or more
containment devices. The kit may also include instructions for mixing one or more
components of the kit and/or ing and mixing a sample (e.g., blood taken from a subject)
and applying to a subject.
The kit may have one or more or all of the components required to draw blood from a
patient, process the sample into platelet trate or WBCs to make a repair material, and
to deliver the repair material to a surgical site. For instance, a kit for withdrawing blood from
a patient may include one or more of the items required for such a procedure. For example,
typically when an injection is to be made, the patient's skin is cleansed with a disinfecting
agent, such as an alcohol wipe; then a second disinfecting agent, such as iodine or Betadine
may be applied to the skin; an area is usually isolated with a tourniquet to restrict the blood
flow within the artery or vein making the vessel more visible before the needle is ed, a
needle attached to a collection device, such as a vacutainer tube is injected through the
patient's skin to withdraw the blood; the needle is then removed and wiped clean; and the
puncture site is d with an absorbent pad until after hemostasis.
The kit may also contain substances ed for administration to a patient prior to
the blood being drawn for use as a repair material. For example, the kit may contain a
specific dose of a growth factor known to result in increased circulating monocyte
concentration so the blood drawn at the time of surgical repair is more favorable for
regeneration of the injured tissue.
The ories included may be specifically ed to allow the practitioner to
aw blood from the patient. For instance, the accessories may include one or more of
the following a tourniquet, a skin penetration instrument, a device for g blood, a
collection tube, disinfecting agents or post-injection bleeding patches.
The skin penetrating instrument for initiation of blood flow may be a conventional
device such as a needle. The needle may be single or double ended and may be of any gauge,
preferably 21 or 23 gauge. It optionally has a safety , may be attached to a needle hub,
and preferably is used with a conventional tube holder. The needle may also be part of a
conventional syringe assembly including barrel and plunger. The needle may be part of a
conventional blood collection set in which a penetrating needle having a grasping means,
such as wings, is ted via a hub and tubing to a delivery needle for puncture of a
septum of an evacuated tube.
The device for housing the blood may be any type of container for receiving the blood
sample, such as, for example, a e barrel or it may be a device to which the blood
sample is transferred following tion, for example a tube. Preferred devices for housing
the blood are conventional tubes or vials having a closed end and an open end. Such tubes
may have an internal volume of 100 μl to 100 ml. Devices to house the blood after it has
been collected include for instance, vials, centrifuge tubes, vortex tubes or any other type of
container. The device for receiving the blood may be an evacuated tube in which the open
end is covered by a puncturable septum or r, such as a vacutainer tube. Evacuated
tubes are generally used with a tional tube holder and blood collection set for
tion of multiple larger blood samples, and may contain any of a variety of conventional
blood analysis ves, such as anticoagulants. Preferred anticoagulants are e and
ethylenediaminetetra acetic acid (EDTA).
The , which contains the platelets, may be used together with other
components of the blood or it may be separated from the whole blood. Any separation
technique can be utilized, for example, sedimentation, centrifugation or filtration.
fugation can be carried out at about 500 g for about 20 minutes to obtain platelets. The
supernatant, which contains the plasma, can be removed by standard techniques. Filtration
can be carried out by passing the whole blood through a suitable filter that separates blood
cells from plasma.
Optionally the kits may include disinfecting agents and post-injection bleeding
patches. A means for sterilizing the patient's skin in the area of intended puncture, such as a
disinfecting agent may be provided. A typical and tional disinfecting agent is a piece
of fabric commonly referred to as a gauze combined with a disinfectant. Some typical
disinfecting agents include rubbing alcohol, antibacterial agents, iodine, and Betadine, which
may or may not be provided with application pads in individually sealed packets. The postinjection
bleeding patch can also vary from a relatively simple gauze pad plus adhesive strips,
to a bandage.
When a blood draw is to be made, the tioner may open the sealed kit; isolate a
selected region of the patient's body, such as the lower arm, with the tourniquet to restrict the
blood flow within the region and make the blood vessels more visible; clean the injection site
with one or more of the sterilizing agents; attach the needle to the collection tube; inject the
needle into the patient's blood vessel and collect the blood sample in the tube; withdraws the
needle from the skin; and covering the puncture site with an absorbent pad. The blood may
then be processed to produce a trate of platelets or white blood cells.
The kit may have a variety of forms, such as a blister pouch, a shrink wrapped pouch,
a vacuum sealable pouch, a sealable thermoformed tray, or a similar pouch or tray form, with
the accessories loosely packed within the pouch, one or more tubes, ners, a box or a
bag.
The kit may be sterilized after the ories are added, thereby allowing the
individual accessories in the container to be otherwise unwrapped. The kits can be sterilized
using any appropriate sterilization techniques, such as radiation sterilization, heat
ization, or other sterilization methods known in the art.
The kit may also contain any other component needed for the intended purpose of the
kit. Thus, other components may be a fabric, such as gauze, for removing the disinfecting
agent after the sterilizing step or for covering the puncture wound after the sample is drawn.
Other optional components of the kit are disposable gloves, a support for the device for
holding blood after the sample is taken, adhesive or other device to maintain the fabric in
place over the re wound.
The kit may include able components ed sterile in disposable packaging.
The kit may also include other components, depending on the specific application, for
example, containers, cell media, salts, buffers, reagents, syringes, needles, etc.
EXAMPLES
EXAMPLE 1: Comparison of the effects of multiple et scaffolds versus a single intact
scaffold on ligament repair.
Methods
Study Design
IACUC approvals were obtained prior to initiating the study. Sixteen late adolescent
Yucatan mini-pigs underwent ACL transection and were then randomized to hanced
ACL reconstruction with BPTB allograft using a bioactive scaffold(s) and bio-enhanced ACL
repair using the same bioactive hydrophilic scaffold(s). The animals within each treatment
group were allowed to heal for 12-months, respectively, at which time the hind limbs were
harvested.
Preparation of the extra-cellular matrix scaffold
The bioactive hydrophilic lds (MIACH, Boston Children’s Hospital, Boston MA)
were manufactured as previously described.28 A slurry of extracellular matrix proteins was
produced by solubilizing bovine connective tissue. The collagen concentration was adjusted to
a minimum of 10mg/ml and lyophilized. For the bio-enhanced ACL truction group, the
scaffold was a porous hollow cylinder with an outer diameter of 22mm, inner diameter of
10mm, and length of 30mm.28 For the bio-enhanced ACL repair group, the scaffolds were a
porous er 22mm in diameter and 30mm long15. All sponges were stored at -20oC until
the day of surgery. At the time of y, scaffolds were either ted either as intact
cylinders, or as multiple pieces of the cylinder. When implanted in the joint, the bioactive
scaffolds, platelets were added as a repair material.
al technique: ACL transection
A medial arthrotomy was created and the fat-pad partially ed to expose the ACL.
The ACL was cut between the proximal and middle thirds of the ligament with a scalpel. A
Lachman test was performed to verify ACL transection. The knee was then irrigated with 500
cc of normal saline. For those animals assigned to receive no treatment, the incision was closed
in layers as usly described.38
Surgical Technique: Bio-enhanced ACL reconstruction
Following ACL transection, an ACL reconstruction procedure was performed using
fresh-frozen bone-patellar tendon-bone afts harvested from age, weight, and gender
matched donor animals as previously described.15 The entire patellar tendon (~10mm in width)
was used for the soft tissue portion of the graft while the bone plugs were trimmed to 7mm
diameter. Femoral graft fixation was achieved with a 6x20mm bio-absorbable interference
screw (Biosure; Smith & Nephew, Andover, MA). The graft was then manually preconditioned
in tension twenty times. The rical extracellular matrix based scaffold was
threaded onto the graft and positioned to cover the intra-articular soft tissue portion and
whether the scaffold was delivered in its intact form or in multiple sections was recorded. The
distal bone plug was then seated retrograde into the tibial tunnel and fixed to the tibia using a
second 6mm interference screw and an extracortical tibial button. 3cc of autologous blood
containing platelets were used to saturate the scaffold in situ. The incisions were closed in
layers after ten s.
Surgical Technique: Bio-enhanced ACL repair
Bio-enhanced ACL repair was performed as previously described.28 In brief, an
Endobutton carrying three looped sutures was passed thru a 4mm femoral tunnel and flipped.
Two of the sutures were ed through the scaffold. The scaffold was maintained outside
the knee while the sutures were placed into a predrilled tibial tunnel. The cylindrical scaffold
was then slid along the sutures into the notch and note was made if the scaffold was intact at
delivery or delivered as multiple transverse sections. The sutures were pulled tight and fixed
extracortically over the tibia using a button with the knee in maximum extension (30 degrees).
The remaining suture was tied to a Kessler suture of #1 Vicryl (Ethicon, Somerville, NJ) which
had been placed in the tibial stump of the ACL. 3cc of autologous blood containing platelets
were used to saturate the scaffold in situ. The incisions were closed in layers after ten s.
Following surgery, all s were housed for four weeks in individualized pens and
were then shipped to a farm for long-term porcine care (Coyote ting Corporation Inc,
Douglas, MA). After 6- and 12-months of g, the animals were ized and the limbs
harvested. The knees were immediately frozen at -20oC until mechanical testing.
hanical testing
The knees were prepared for biomechanical g as previously described.15 The
biomechanical testing ures (i.e., AP knee laxity, structural properties) were performed
using a servohydraulic load frame and custom es (MTS Systems Corporation, Eden
Prairie, MN).15 All investigators were blinded to the treatment group during specimen
ation and biomechanical testing. AP knee laxity was measured at 30°, 60°, and 90° of
knee flexion by ng fully-reversed, sinusoidal anterior-posterior directed shear loads of
±40N at 0.0833 (1/12) Hz for 12 cycles at each knee angle.13 The structural properties of the
ligaments and grafts were determined using a standardized failure test protocol.18 Before
starting the tensile test, the femur was lowered until the load across the joint surface was +5N
of compression. A ramp at in was initiated and the load-displacement data were
recorded at 100Hz.21 The yield load, failure load, linear stiffness, displacement to 5N (a
“slackness” parameter) and the energy to failure were ined from the MTS loaddisplacement
data.
RESULTS
All animals survived to the one year post op time point. There were no infections or
incidence of arthrofibrosis. The mean yield load of the group treated with a bio-enhanced repair
using an intact longitudinal scaffold was 133N, while that using a scaffold which was delivered
in several large sections was 517N and the yield load when the scaffold was delivered in
multiple small sections was 880N. The mean maximum loads were 155N, 673N and 956N
respectively for the three groups. Linear stiffness was 35N, 142N and 185N respectively for
the three groups (intact, few sections, many sections).
CONCLUSION
This study demonstrated that delivery of the scaffold used for bio-enhanced ACL repair
was more effective when performed by delivering the scaffold in multiple pieces rather than as
an intact longitudinal structure that coursed the entire distance between the bones or ligament
ends.
Example 2 Clinical Studies
Methods
Patients age 18 to 35 with a complete ACL tear who were less than one month from
injury and who had at least 50% of the length of the ACL attached to the tibia on their preoperative
MRI were eligible to enroll in the BEAR group. Patients with a complete ACL tear
who were within three months of injury were eligible to enroll in the ACL reconstruction group.
Only patients ined to benefit from surgical ention with autograft hamstring tendon
graft were ered for this study. Patients were excluded from either group if they had a
history of prior surgery on the knee, history of prior infection in the knee, or had risk factors
that might adversely affect healing (nicotine/tobacco use, corticosteroids in the past six months,
chemotherapy, diabetes, inflammatory tis). Patients were excluded if they had a displaced
bucket handle tear of the medial us which required repair; all other meniscal injuries
were included. Patients were also excluded if they had a full ess chondral injury, a Grade
III MCL injury, a concurrent complete patellar dislocation, or an ive posterolateral corner
injury. Two hundred and forty two patients presenting with an ACL injury were ed for
participation in this study. Patients were identified as possible candidates if they scheduled an
appointment in the Sports Medicine Division with a new knee injury and had an MRI
confirming an ACL tear or if they contacted the research coordinator after hearing about the
study. Of the 242 patients screened, 22 were enrolled in the study, of which two were ed
before surgery.
Surgical que
After the induction of general anesthesia, an examination was performed to verify the
positive pivot shift on the injured side and to record the Lachman, range of motion and pivot
shift exam results on both knees. A knee arthroscopy was performed and meniscal injuries
were treated if present. The tibial aimer (ACUFEX Director Drill Guide, Smith and Nephew,
Andover, MA) was used to place a 2.4mm guide pin up through the tibia in the tibial
footprint of the ACL in some patients (in some patients, the holes were drilled near but not
within the footprints. This difference did not impact the results.) and then the pin was
overdrilled with a 4.5 mm reamer (4.5 mm Endoscopic Drill, Smith and Nephew, Andover,
MA). A guide pin was placed in the femoral ACL footprint, drilled up through the femur and
then overdrilled with the 4.5 mm reamer. A 2 inch tomy was made at the medial border
of the patellar tendon and a whip stitch of #2 Vicryl was placed into the tibial stump of the
torn ACL. Two #2 Ethibond sutures were looped through the two center holes of a cortical
button (Endobutton, Smith & Nephew, r, MA). The #2 Vicryl suture from the tibial
stump had the free ends passed through the cortical button and the button carrying the
Ethibond and Vicryl s was passed through the femoral tunnel and d on the
lateral femoral cortex. Both of the looped sutures of #2 nd (four matched ends) were
passed through the scaffold, and keeping the scaffold out of the joint, the long Ethibond
s were passed through the tibial tunnel and clamped. The hydrophilic ld was then
passed up along the sutures into the femoral notch with note being made of whether the
scaffold arrived intact or in multiple sections. 10 cc of autologous blood obtained from the
antecubital vein was added to the hydrophilic scaffold. The free ends of the Ethibond sutures
were pulled tight and tied over a second cortical button on the anterior tibial cortex with the
knee in full extension. The remaining pair of suture ends coming through the femur was tied
over the femoral cortical button to bring the ACL stump into the scaffold using an
arthroscopic surgeon's knot and knot . The arthrotomy was closed in layers.
Results:
In all patients, the scaffolds were in multiple pieces after placement in the notch. These
patients had evidence of healing of the ACL despite this as noted in their post-operative MRIs
(shown in Fig. 8). In Fig. 8A, the torn ACL is visualized. Fig. 8B demonstrates the appearance
of the healing ACL at 3 months. The degree of healing is shown at 6 months following surgery
in Fig. 8C and at 12 months in Fig. 8D. The results demonstrate good healing of the ACL when
the scaffold is delivered in multiple sections, in contrast to the expectation in the art. All knees
in the study were stable at the six month post-operative time point, trating effective
healing of the injured ACL. The results of Lachman Testing are shown in Figs. 9 and 10.
Example 3 Large animal model showing efficacy of placement of multiple scaffolds around an
ACL graft
Methods:
Twenty one Yucatan minipigs underwent ACL ction and truction with a
bone-patellar tendon-bone allograft. Seven had no augmentation of the graft placed, seven
had a cylindrical graft which was continuous along the entire length of the ACL graft, and
seven had sets of le scaffolds packed in front of the graft. All s survived for 12
weeks. Biomechanical testing of the ACL strength were performed at that time point.
The AP laxity values for the knees treated with the sets of multiple scaffolds packed
in front of the graft were lower than that of the untreated ACLs and that of the ACLs treated
with the continuous scaffold (at 30 degrees, the values were 3.3 +/- 1.7mm, 8.1 +/- 3 mm and
7 +/- 3 mm respectively, at 60 degrees, the values were 9 +/- 1 mm, 13 +/- 2.4mm and 11 +/-
3 mm respectively and at 90 degrees, the values were 8.4 +/- 1mm, 13.2 +/- 2.6mm and 13.0
+/- 3 mm respectively). The p value for comparisons of standard ACL truction vs the
fragmented group were p= 0.00 for all three angles tested and vs the continuous scaffold were
p=0.01 for the testing at 30 degrees, p = 0.07 at 60 degrees and p = 0.00 at 90 s.
The displacement to 5N on mechanical testing was also significantly better in the sets
of multiple lds group when tested against ACL reconstruction (p=0.00) and continuous
scaffold reconstruction (p=0.06).
Thus, use of the sets of multiple scaffolds resulted in less abnormal knee laxity and
better healing when used to enhance ACL surgery, quite surprisingly, in contrast to a single
scaffold.
Example 4: Clinical studies of ld-enhanced repair with blood cells
Patients age 13 to 35 with a complete ACL tear who were less than one month from
injury and who had at least 50% of the length of the ACL attached to the tibia on their preoperative
MRI were recruited for a randomized control trial of ACL repair using indirect
fixation of the sutures to femur and tibia and set of multiple scaffolds (from scaffold which was
noted to be in le pieces) prior to wound closure.
al Technique
After the induction of general anesthesia, an examination was performed to verify the
positive pivot shift on the injured side and to record the Lachman, range of motion and pivot
shift exam results on both knees. A knee arthroscopy was performed and meniscal es
were treated if present. The tibial aimer (ACUFEX Director Drill Guide, Smith and Nephew,
Andover, MA) was used to place a 2.4mm guide pin up through the tibia in the tibial
footprint of the ACL in some patients (in some patients, the holes were drilled near but not
within the footprints. This difference did not impact the results.) and then the pin was
overdrilled with a 4.5 mm reamer (4.5 mm Endoscopic Drill, Smith and Nephew, Andover,
MA). A guide pin was placed in the femoral ACL footprint, drilled up h the femur and
then overdrilled with the 4.5 mm reamer. A 2 inch arthrotomy was made at the medial border
of the patellar tendon and a whip stitch of #2 Vicryl was placed into the tibial stump of the
torn ACL. Two #2 Ethibond sutures were looped h the two center holes of a cortical
button (Endobutton, Smith & Nephew, Andover, MA). The #2 Vicryl suture from the tibial
stump had the free ends passed through the cortical button and the button carrying the
Ethibond and Vicryl sutures was passed h the femoral tunnel and d on the
lateral femoral cortex. Both of the looped sutures of #2 Ethibond (four matched ends) were
passed through the scaffold, and keeping the scaffold out of the joint, the long Ethibond
s were passed through the tibial tunnel and clamped. The scaffold was then passed up
along the sutures into the femoral notch with note being made of whether the scaffold arrived
intact or in multiple sections. 10 cc of autologous blood obtained from the bital vein
was added to the scaffold. The free ends of the Ethibond sutures were pulled tight and tied
over a second cortical button on the anterior tibial cortex with the knee in full ion. The
remaining pair of suture ends coming through the femur was tied over the femoral cortical
button to bring the ACL stump into the scaffold using an arthroscopic surgeon's knot and
knot . The arthrotomy was closed in layers. A complete blood count was obtained from
the autologous blood added to the ld in surgery.
Results:
In all patients, the scaffolds were in multiple pieces after placement in the notch. The
results demonstrate good healing of the ACL when the ld is delivered in multiple
sections, in contrast to the expectation in the art. All knees in the study were stable at the six
month perative time point, demonstrating effective healing of the injured ACL. A
noninvasive measure of ligament strength was performed. The number of monocytes in the
repair material added to the fragmented scaffold significantly improved the predicted th
of the repair (), as did the number of basophils (). A greater number of
granulocytes (); however, resulted in lower strength of the healing ligament. A higher
number of eosinophils () in the repair material was associated with a larger healing
ligament volume.
EQUIVALENTS
All references, patents and patent applications disclosed herein are incorporated by
reference with respect to the subject matter for which each is cited, which in some cases may
encompass the entirety of the document.
The indefinite es “a” and “an,” as used herein in the ication and in the
, unless clearly indicated to the contrary, should be understood to mean “at least one.”
It should also be understood that, unless clearly indicated to the contrary, in any
methods claimed herein that include more than one step or act, the order of the steps or acts
of the method is not necessarily limited to the order in which the steps or acts of the method
are recited.
In the claims, as well as in the specification above, all transitional phrases such as
“comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,”
“composed of,” and the like are to be tood to be open-ended, i.e., to mean including
but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of”
shall be closed or semi-closed tional phrases, respectively, as set forth in the United
States Patent Office Manual of Patent Examining Procedures, Section 2111.03.
Claims (1)
1-20 mm in , wherein the lds are compressible expandable scaffolds. 5 2. The device of claim 1, wherein the scaffolds are collagen sponges. 3. The device of claim 1, wherein the scaffolds are hydrophilic. 4. The device of claim 2, wherein the collagen sponges comprise type I soluble collagen and n the collagen sponges are prepared from a on of solubilized collagen in a concentration of greater than 5 and less than or equal to 50 mg/ml. 10 5. The device of claim 2, wherein the collagen sponges comprise type I soluble collagen and wherein the en sponges are prepared from a solution of solubilized en in a concentration of greater than 50 and less than or equal to 500 mg/ml. 6. The device of claim 1, wherein each of the scaffolds in the set are the same. 7. The device of claim 1, wherein at least one of the scaffolds in the set is different 15 from the other scaffolds in the set. 8. The device of claim 7, wherein the at least one different scaffold has a different size than the other scaffolds. 9. The device of claim 7, wherein the at least one different scaffold has a different shape than the other scaffolds. 20 10. The device of claim 8, n the at least one different scaffold is shaped as a sphere. 11. The device of claim 8, wherein the at least one different scaffold is shaped as a cylinder. 12. The device of claim 7, wherein the at least one different scaffold is comprised of a 25 different biodegradable polymer than the other scaffolds. 13. The device of claim 11, wherein the scaffolds are sed of collagen. 14. The device of claim 11, wherein the scaffolds are comprised of a non-collagen polymer. 15. The device of any one of claims 1 to 14, wherein the set of scaffolds have a total surface area that is greater than a single scaffold used to repair a nt or tendon injury. 5 16. A kit, comprising the device of any one of claims 1 to 15 and further comprising one or more containers to house the set of distinct biodegradable scaffolds, and instructions for surgical repair of a ligament or tendon using the device. 17. The kit of claim 16, further comprising a nment device housed in one or more of the containers. 10 18. The kit of claim 17, wherein the containment device is a suture. 19. The kit of claim 18, wherein the scaffolds are threaded onto the . 48146580, v. 1
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662358661P | 2016-07-06 | 2016-07-06 | |
US62/358,661 | 2016-07-06 | ||
PCT/US2017/040865 WO2018009637A1 (en) | 2016-07-06 | 2017-07-06 | Indirect method of articular tissue repair |
Publications (2)
Publication Number | Publication Date |
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NZ748139A NZ748139A (en) | 2021-04-30 |
NZ748139B2 true NZ748139B2 (en) | 2021-08-03 |
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