WO2025096889A1 - Échafaudage synthétique et ses utilisations - Google Patents

Échafaudage synthétique et ses utilisations Download PDF

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Publication number
WO2025096889A1
WO2025096889A1 PCT/US2024/054050 US2024054050W WO2025096889A1 WO 2025096889 A1 WO2025096889 A1 WO 2025096889A1 US 2024054050 W US2024054050 W US 2024054050W WO 2025096889 A1 WO2025096889 A1 WO 2025096889A1
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WO
WIPO (PCT)
Prior art keywords
scaffold
spacer
sleeve
synthetic scaffold
tissue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/054050
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English (en)
Inventor
James H. Chapman
Cato T. Laurencin
Amir A. ABEDINI
Chinedu C. UDE
Lakshmi S. Nair
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University of Connecticut
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University of Connecticut
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Publication of WO2025096889A1 publication Critical patent/WO2025096889A1/fr
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Anticipated expiration legal-status Critical

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Classifications

    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04C—BRAIDING OR MANUFACTURE OF LACE, INCLUDING BOBBIN-NET OR CARBONISED LACE; BRAIDING MACHINES; BRAID; LACE
    • D04C1/00—Braid or lace, e.g. pillow-lace; Processes for the manufacture thereof
    • D04C1/02—Braid or lace, e.g. pillow-lace; Processes for the manufacture thereof made from particular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/08—Muscles; Tendons; Ligaments
    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04C—BRAIDING OR MANUFACTURE OF LACE, INCLUDING BOBBIN-NET OR CARBONISED LACE; BRAIDING MACHINES; BRAID; LACE
    • D04C1/00—Braid or lace, e.g. pillow-lace; Processes for the manufacture thereof
    • D04C1/06—Braid or lace serving particular purposes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0023—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in porosity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/003—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in adsorbability or resorbability, i.e. in adsorption or resorption time
    • D—TEXTILES; PAPER
    • D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10B2509/00—Medical; Hygiene

Definitions

  • the invention disclosed herein relates to a synthetic scaffold and uses thereof, and in particular use as augmentation in soft tissue and/or ligament regeneration.
  • ACL anterior cruciate ligament
  • the present disclosure provides, in at least one aspect, synthetic scaffold devices including a sleeve; and a spacer positioned within the sleeve to create a hollow space configured to receive a tissue graft.
  • the spacer comprises at least one of a tube, a rod, a spring, or combinations thereof.
  • the spacer comprises a biodegradable and biocompatible material selected from the group consisting of poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.
  • the spacer is removable.
  • the spacer is expandable.
  • the expandable spacer comprises at least one of: an inflatable component configured to be expanded using a biocompatible fluid; or a mechanical expansion mechanism comprising at least one of a collapsible mesh structure or telescoping segments.
  • the sleeve comprises a component/s (also called as a sleeve component) that is braided, woven, knitted or any combination thereof.
  • the sleeve comprises a braided component.
  • the sleeve comprises a woven component.
  • the sleeve comprises a knitted component.
  • the sleeve comprises a braided, a woven, and a knitted component.
  • the sleeve comprises a braided and a woven component.
  • the sleeve comprises a braided and a knitted component.
  • the sleeve comprises a woven and a knitted component.
  • the sleeve comprises biodegradable polymer fibers comprising at least one of poly-L-lactic acid (PLLA), poly(DL)- lactic acid (PLA), or combinations thereof.
  • the sleeve component terminates in first and second attachment ends and includes a middle region that differs from both of said attachment ends in at least one of size, braiding angle, porosity, or mechanical strength.
  • the device further comprises a tissue graft positioned within the hollow space, wherein the tissue graft comprises at least one of an autograft, an allograft, or a xenograft.
  • the present disclosure provides, in at least one aspect, methods of making a synthetic scaffold device, including forming a braided component, positioning a spacer within the sleeve component during formation to create a hollow space, and configuring the hollow space to receive a tissue graft, wherein the spacer comprises either a removable spacer configured to be removed before or during implantation, or a biodegradable spacer configured to degrade after implantation.
  • the method further includes selecting the biodegradable spacer to have a degradation rate coordinated with tissue healing timeline.
  • the method further includes removing the spacer when the spacer is removable, inserting a tissue graft into the hollow space, and implanting the synthetic scaffold device and tissue graft in a subject.
  • the present disclosure provides, in at least one aspect, synthetic scaffold systems including a sleeve, a spacer positioned within the sleeve, wherein the spacer includes either a removable spacer configured to be removed to create a hollow space for receiving a tissue graft, or a biodegradable spacer configured to degrade in vivo after implantation, and a tissue graft configured to be received within the hollow space.
  • the biodegradable spacer comprises a material selected from the group consisting of poly-L-lactic acid (PLLA), poly(DL)- lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.
  • PLLA poly-L-lactic acid
  • PLA poly(DL)- lactic acid
  • PGA polyglycolic acid
  • PLGA poly(lactic-co-glycolic acid)
  • the tissue graft includes at least one of a heterogeneous autograft, a bone-patella-bone autograft, or an Achilles allograft or other soft tissue graft such as tibialis anterior, hamstring, quad tendon.
  • the sleeve comprises a mixture of high-density and low- density biodegradable polymer fibers configured to modulate degradation rate in vivo.
  • the present disclosure provides, in at least one aspect, methods of treating a subject including providing a synthetic scaffold device comprising a braided component, and a spacer positioned within the sleeve, when the spacer is removable, removing the spacer to create a hollow space, when the spacer is biodegradable, maintaining the spacer within the sleeve, inserting a tissue graft into the hollow space, and implanting the synthetic scaffold device and tissue graft to repair, reconstruct, or replace a ligament or tendon in the subject.
  • the method further comprises selecting the biodegradable spacer to have a degradation profile matched to a tissue healing timeline.
  • the method includes incorporating a bioactive material into the synthetic scaffold device prior to implanting.
  • the tissue graft and synthetic scaffold device are pre-assembled after spacer removal and stored prior to implanting, and when the spacer is biodegradable, the tissue graft, spacer, and synthetic scaffold device are preassembled and stored prior to implanting.
  • Figure 1 is a synthetic scaffold and method of manufacture in accordance with the present disclosure.
  • Figure 2 is a method of incorporating bioactive materials to a synthetic scaffold in accordance with the present disclosure.
  • Figure 3 depicts individual steps of employing a mold to form a synthetic scaffold in accordance with the present disclosure.
  • Figure 4 provides a stress strain graph of an autograft and LUCA device on the left, and a stress-strain graph of a Karakow suture and LUCA device (Achilles Tendon Repair) on the right.
  • Figure 5 is a stress strain graph comparing the mechanical properties of different number of plies in a synthetic scaffold in accordance with the present disclosure.
  • Figure 6 provides a visual illustration of the braiding procedure (Right) and the final product including a braid and a spacer such as tubing (Left).
  • Figure 7 provides a visual illustration of a synthetic scaffold with an expandable spacer in accordance with the present disclosure.
  • Figure 8 depicts the different elements of a LUCA graft in accordance with the present disclosure.
  • Figure 9 depicts isolation of rabbit’s autograft for fabrication of a synthetic scaffold in accordance with the present disclosure.
  • Figure 10 depicts the process of integrating the autograft into the braid involved the use of a suture needle. One end of the autograft was affixed to the suture yarn, and subsequently, the graft was threaded through the tubing. Following this, the tubing was extracted, leaving the autograft positioned at the center of the braid, resulting in the final LUCA graft.
  • Figure 11 depicts the surgical reconstruction of the rabbit’ s ACL using cadaveric tissue. The LUCA graft was implanted subsequent to the creation of bone tunnels.
  • Figure 12 depicts a LUCA graft inside of knee after reconstruction surgery on rabbit’s cadaver.
  • Figure 13 is a stress-strain graph of the LUCA scaffold.
  • U.S. Pat. No. 8,945,218 discloses a degradable, polymeric fiber-based, three- dimensional braided ligament or tendon scaffold for use as graft materials in ligament and tendon repair, reconstruction and replacement, however, soft tissues like autograft, allograft, and xenograft cannot be used with this braided scaffold as it lacks additional support for the implanted soft tissue. This important drawback is overcome by the novel design of the disclosed scaffold herein.
  • Figure 1 provides a representative embodiment of the disclosed scaffold and method.
  • a synthetic scaffold or device including a synthetic, biodegradable sleeve including a braided component, and a spacer such as a tube.
  • the “spacer” as used herein means a device or a piece used to create or maintain a desired amount of space (for example, space within a braided component to hold a ligament and/or soft tissue such as autograft, allograft, and xenograft).
  • a synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid and a spacer.
  • synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid; a spacer; and a soft tissue such as autograft, allograft, and xenograft.
  • any suitable spacer can be used, some nonlimiting examples of the spacer are a tube, a rod, a spring, or a combination thereof.
  • the spacer is biocompatible.
  • the spacer is removable.
  • the spacer is a tube. Any suitable tube can be used.
  • the tube is made from biocompatible materials.
  • the spacer is a rod.
  • the spacer is expandable.
  • the expandable spacer may comprise an inflatable component that can be expanded using air, saline, or other biocompatible fluids to achieve different diameters.
  • the expandable spacer may include a mechanical expansion mechanism, such as a collapsible mesh structure or telescoping segments, that can be adjusted to various diameters through mechanical actuation.
  • a mechanical expansion mechanism such as a collapsible mesh structure or telescoping segments
  • This expandability feature allows surgeons to customize the internal diameter of the scaffold to accommodate different sizes of autografts, allografts, or xenografts during the surgical procedure.
  • the expandable spacer can be designed to maintain its expanded configuration temporarily during graft placement and then be deflated or collapsed for removal, leaving the graft securely positioned within the braided structure.
  • synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid (a sleeve) and a soft tissue such as autograft, allograft, and xenograft.
  • a synthetic scaffold/device that offer additional structural support.
  • a synthetic scaffold/device that offers a favorable biologic environment for healing and soft tissue and/or ligament regeneration. Any suitable soft tissue and/or ligament can be used.
  • the soft tissue and ligaments include a heterogeneous or other type of autograft/allograft - such as a bone-patella-bone autograft that includes bony ends and a tendon in between, or an achilles allograft that includes a bone plug on one end and tendon on the other end or a hamstring or quad tendon allograft/autograft.
  • the device can incorporate and conform to these diverse uses of grafts.
  • the scaffold is for a soft tissue and/or ligament regeneration in a subject.
  • the scaffold is for a soft tissue regeneration such as muscle or tendon in a subject.
  • the scaffold is for ligament regeneration in a subject.
  • the scaffold is for nerve, vascular, fascial and/or connective tissue regeneration.
  • the sleeve/braid includes biodegradable polymer fibers.
  • the fiber includes at least one lactic acid polymer.
  • the spacer such as a tube within the braided component may possess sufficient biocompatibility to avoid interfering with autografts, allografts, or xenografts, thereby preventing toxicity.
  • the spacer’s flexibility enables it to be gathered by a collector post-braiding, facilitating continuous production.
  • the spacer’s (such as a tubing) inner diameter is large enough to allow the insertion of autograft, allograft, and xenograft.
  • the scaffold may incorporate bioactivc materials to enhance tissue regeneration and integration.
  • incorporating bioactive materials may involve several discrete steps. First, a mold is created to form the desired spacer configuration. The mold is then filled with a selected bioactive solution or hydrogel, such as collagen or gelatin. The graft is carefully positioned within the mold containing the bioactive material. For hydrogel-based bioactive materials, the combined device and hydrogel can be removed from the mold and used directly in surgical procedures. For other bioactive solutions, the graft and bioactive material combination undergoes a drying process. Once the drying process is complete, the final product - consisting of the graft integrated with the bioactive materials - is removed from the mold and is ready for use. This process ensures uniform distribution and incorporation of the bioactive materials throughout the scaffold structure.
  • the processing method varies depending on the type of bioactive material used.
  • the device-hydrogel combination can be utilized immediately after removal from the mold, maintaining the hydrogel’s natural properties.
  • various drying methods may be employed, including: lyophilization (preserves the structural integrity of the bioactive materials while creating a porous structure), air drying (allows for gradual dehydration under controlled conditions), or oven drying (provides accelerated drying under precise temperature control). The choice of drying method is determined by the specific properties of the bioactive material and the desired final characteristics of the scaffold.
  • the braid includes at least one biodegradable polymer.
  • the biodegradable polymer includes poly-L-lactic acid (PLLA) and poly(DL)-lactic acid (PLA).
  • the scaffold/device allows for an incorporation of a host tissue autograft, allograft, or xenograft.
  • the braid is prepared by a three dimensional braiding technique.
  • the braid includes biodegradable polymer fibers, wherein the braid terminates in three-dimensional, braided first and second attachment ends and the braid includes a three-dimensional, braided middle region that differs from both of said attachment ends in size, braiding angle, porosity, and mechanical strength to facilitate a differential cellular response in said middle region as compared with said first and second attachment ends.
  • the sleeve/braid has a substantially circular cross-section. In an embodiment, the sleeve/braid has a substantially rectangular cross- section.
  • the biodegradable polymer fibers include poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), or a combination thereof. In an embodiment, the biodegradable polymer fibers include poly-L- lactic acid (PLLA). In an embodiment, the biodegradable polymer fibers include poly(DL)-lactic acid (PLA). In an embodiment, the biodegradable polymer fibers include poly-L-lactic acid (PLLA) and poly(DL)-lactic acid (PLA).
  • the sleeve/braid is formed from a plurality of bundles comprising about 5 to about 120 fibers per bundle. In an embodiment, the sleeve/braid is formed from a plurality of bundles comprising about 10 to about 60 fibers per bundle.
  • the braid is formed using a three dimensional braiding technique that utilizes a row and column braider.
  • the scaffold is adapted to repair, reconstruct, or replace an anterior cruciate ligament (ACL).
  • the said braid terminates in three-dimensional, braided first and second attachment ends and said braid includes a three-dimensional, braided middle region that differs from both of said attachment ends in size, braiding angle, porosity, and mechanical strength.
  • a method including implanting a scaffold disclosed herein in a subject or a patient in need thereof.
  • the method includes implanting the scaffold to repair, reconstruct, or replace an anterior cruciate ligament of the subject.
  • the braid is formed using a three dimensional braiding technique that utilizes a rectangular and/or circular braider.
  • the method includes implanting the scaffold to repair, reconstruct or replace other soft tissues such as muscle, tendon, including but not limited to the rotator cuff or a combination thereof.
  • the braid has a substantially circular cross-section.
  • the braid has a substantially rectangular cross-section.
  • the braid includes braided bundles of multi-filament, biodegradable polymer fibers.
  • the disclosed scaffold can augment traditional ACL reconstruction by providing early mechanical strength, support, and other biologic healing properties to facilitate healing, regeneration, and/or ligamentization to the tendon autograft, in addition to allograft, and xenograft.
  • the device can be used for muscle, tendon, ligament, bone, nerve, vessel, and/or cutaneous regeneration.
  • a tom rotator cuff tendon or other tendon or ligament can be repaired with the device described herein where the device can attach to, wrap around, or otherwise combine with the tendon or ligament at the site of repair to facilitate both increased mechanical strength and other biologic healing properties to facilitate healing and/or regeneration.
  • the scaffold can decrease morbidity intra-operatively, and post-operatively prevent the need for revision surgery.
  • Figure 4 illustrates how an augmented graft of the present disclosure compares in mechanical strength to conventional autograph techniques.
  • the device may significantly decrease post-operative morbidity.
  • the synthetic scaffold/device offers a favorable biologic environment for healing and soft tissue and/or ligament regeneration. Post-operative rehabilitation and time to return to activity can be significantly decreased if the patient has the device implanted, which can allow early structural support to the knee joint while the autograft, allograft, or xenograft matures.
  • the terms Autograft, allograft, and xenograft as used herein have the same meaning as commonly understood by one of ordinary skill in the art. For example, autograft tissue is harvested from the patient/ subject and allograft tissue is taken from a donor or a human cadaver used to reconstruct or replace the anterior cruciate ligament, while xenograft tissue is from animal tissue.
  • the present disclosure provides a new geometric design and method of fabrication to allow for the protection and incorporation of autograft, allograft, and xenograft.
  • a standalone synthetic graft is used for ACL reconstruction/replacement without any spacer or other tissue resulting suboptimal outcomes and long recovery times.
  • the present disclosure provides a significant improvement to this technology.
  • the present disclosure has an improved design that will allow for incorporation of autografts, allografts, and xenografts.
  • the disclosed design can also be used for soft tissue repair such as but not limited to ACL repair.
  • the scaffold/device described herein can be wrapped around, fixed to, or otherwise incorporated with host tissue that is to be repaired in situ/in vivo with known surgical techniques.
  • the device provides additional structural support and/or biologic properties to facilitate healing of a repaired ligament, ACL or other soft tissue.
  • the disclosed scaffold/device includes poly-L-lactic acid (PLLA) and/or poly(DL)-lactic acid (PLA) braided component that has a unique structure to allow for the incorporation of host tissue autograft, allograft, or xenograft.
  • the scaffold/device includes a braided component that serves as a structural support, with a spacer such as a tube placed at the center of the braid.
  • the unique structure includes a hollow space created by the spacer such as a tube that allows placement of a soft tissue like autograft, allograft, or xenograft.
  • a braiding machine loaded with 24 yarn bobbins was employed.
  • the spacer such as a tube was positioned within the yarns at the center during the braiding process.
  • the mechanical properties can be controlled. A higher number of plies results in higher mechanical strength, but the degradation time also increases.
  • the scaffold may be further enhanced through the incorporation of bioactive materials.
  • the process begins with the creation of a customized mold designed to accommodate both the spacer and the intended bioactive materials.
  • the mold s dimensions and configuration are optimized to ensure uniform distribution of the bioactive materials throughout the scaffold structure.
  • Various bioactive solutions or hydrogels may be utilized, including but not limited to collagen and gelatin, each selected based on their specific regenerative properties and compatibility with the intended tissue type.
  • Figure 6 provides an example fabrication process and resulting possible embodiment of the scaffold, including the braided component or structure and the spacer such as tube.
  • the spacer such as tube enables surgeons to easily insert autografts, allografts, xenografts, or a combination thereof.
  • the spacer is designed to be expandable through either fluid inflation or mechanical means, as shown in Figure 7.
  • the expandable design allows the spacer to be adjusted to various diameters, accommodating different graft sizes and ensuring optimal fit within the braided structure.
  • the spacer can be inflated with sterile saline or air through a valve system, achieving precise diameter control.
  • Mechanical expansion may utilize telescoping segments or expandable mesh designs that can be locked at desired diameters.
  • the spacer such as tube can be subsequently removed, either by deflation in the case of inflatable designs or by collapsing mechanical expansion mechanisms.
  • the spacer such as tube helps to create a hollow space inside the braided component that enables easy insertion of autografts, allografts, xenografts, or a combination thereof.
  • the spacer such as tube can be made of any suitable material, for example, any suitable non-toxic polymer including but not limited to PVC, and PTFE.
  • the spacer such as tube is biocompatible.
  • Figure 8 illustrates an embodiment with the elements of the scaffold, in a combination of soft tissue of (for example, autograft, allograft, or xenograft) integrated with a braided structure.
  • the scaffold may be called as LUCA ligament or graft with a new design wherein the spacer such as tube (not shown in Figure 8) helps to create a hollow space (hollow core) within the scaffold allows for the easy insertion of a tendon autografts, allografts, and/or xenografts.
  • the spacer is removed to create a hollow core or space followed by placement of the autograft, allograft, or xenograft, and the scaffold is implanted in a subject.
  • the autograft, allograft, or xenograft is placed while spacer is still present in the braided structure, and the spacer is removed before implanting the scaffold in a subject.
  • the spacer is not removed from the scaffold and is implanted with the autograft, allograft, or xenograft, and the scaffold in a subject.
  • the spacer includes a biodegradable and biocompatible material. Some examples of the biodegradable and biocompatible material include but are not limited to PLLA, PLA, PGA, PLGA, or a combination thereof.
  • the timing and sequence of spacer removal may be coordinated with the bioactive material application process.
  • the bioactive material may be applied either before or after spacer removal, depending on the specific surgical requirements and desired therapeutic outcomes.
  • the application process is typically completed prior to spacer removal to ensure optimal integration with the scaffold structure.
  • a method for using a synthetic scaffold/device for soft tissue and/or ligament regeneration in a subject is for soft tissue regeneration in a subject.
  • the method is for ligament regeneration in a subject.
  • the method includes providing a scaffold disclosed herein; providing an autograft, allograft, or xenograft; and implanting the scaffold and the autograft, allograft, or xenograft in a subject.
  • a spacer from the scaffold is removed before implanting the scaffold and the autograft, allograft, or xenograft in the subject.
  • a spacer from the scaffold is not removed before implanting the scaffold and the autograft, allograft, or xenograft in the subject.
  • the spacer is biodegradable.
  • the spacer is non-biodegradable.
  • the subject is human.
  • an electrospinning technique can be used to fabricate microfiber nonwoven matrices.
  • the sleeve/braid was formed using a 3-D textile braiding technique.
  • the 3-D textile braiding technique used is a 4-step process which uses a track and column method to create the fiber matrix.
  • other suitable techniques for preparing 3-D braided scaffolds can also be used, such as knitting or weaving fibers.
  • a rabbit’ s autograft was employed.
  • the poly-L- lactic acid (PLLA) and/or poly(DL)-lactic acid (PLA) braided scaffold can be utilized for the insertion of both allograft and xenograft.
  • biodegradable polymers of different density can be used to include both high-density and low-density fibers as a hybrid construct.
  • the braid can vary with a mixture of high and low density fibers which can modulate the degradation rate in vivo and allow optimization of graft maturity through loadsharing balance.
  • bioactive materials may further enhance the scaffold’s biological properties and tissue integration capabilities.
  • the selection of specific bioactive materials can be customized based on the target tissue type and its regenerative requirements, the desired rate of bioactive material release and degradation, compatibility with the chosen polymer density combinations, and/or the intended therapeutic effect (e.g., enhanced cell adhesion, growth factor delivery, anti-inflammatory properties)
  • the degradation rate and mechanical properties of the braid can be modulated.
  • the degradation rate is the rate of destruction of the polymeric braid in the body because of hydrolysis or other degradative process.
  • PLLA fibers arc utilized, other kinds of suitable polymeric and/or biodegradable fibers can be used for making the braid.
  • any suitable biodegradable and/or nonbiodegradable polymers can be utilized, as recognized by experts in this field when reviewing this disclosure.
  • bioactive materials When bioactive materials are incorporated into the scaffold, their degradation characteristics must be considered in conjunction with the polymer degradation rate.
  • the combined degradation profiles of the polymeric scaffold and bioactive materials can be tailored to optimize tissue regeneration by; matching the release rate of bioactive compounds with the tissue healing timeline; ensuring appropriate mechanical support throughout the regeneration process; and/or maintaining an optimal microenvironment for tissue formation and maturation.
  • the favored biodegradable polymers are those that break down through hydrolysis. Any suitable biodegradable polymer that may degrade by other means than hydrolysis can also be used.
  • polymeric fibers suitable for the current invention encompass, but arc not restricted to, fibers composed of poly(hydroxy)esters, such as polylactic acid, polyglycolic acid, and their co-polymers.
  • the preferred biodegradable polymers are lactic acid-based polymers, including poly(L-lactic acid) (PLLA), poly(DL-lactic acid) (PLA), and poly(DL-lactic-co- glycolic acid) (PLGA).
  • the ideal co-monomer ratios for poly(DL-lactic-co-glycolic acid) range from 100:0 to 50:50. Specifically, the most preferred co-monomer ratios fall between 85:15 (PLGA 85:15) and 50:50 (PLGA 50:50). Additionally, blends of PLLA with PLGA, particularly PLGA 85:15 and PLGA 50:50, can also be employed for these scaffolds.
  • biodegradable polymers suitable for the scaffolds in this invention encompass, but are not confined to, polyorthoesters, polyanhydrides, polyphosphazenes, polycaprolactones, polyhydroxybutyrates, degradable polyurethanes, polyanhydrideco-imides, polypropylene fumarates, and polydiaxonane.
  • a xenograft or allograft could be loaded into the scaffold and stored before intra-operative use.
  • the combined scaffold with allograft or xenograft could be sterilized and stored, and used off the shelf/out of cold storage directly as a graft for ACL reconstruction or other soft tissue procedure.
  • Example An autograft in a rabbit cadaver.
  • an embodiment of the disclosed scaffold was incorporated with a segment of the rabbit’ s own tendon as an autograft into the PLLA braid. Subsequently, this scaffold, also referred to as the LUCA graft, was utilized for an ACL reconstruction procedure in the rabbit cadaver, as shown in Figures 11 and 12. After successful ACL reconstruction in this rabbit model, The LUCA graft added significant stability to the knee. Lachmann test revealed firm endpoint and minimal tibial translation under stress. [0066] As shown in Table 1 and Figure 13, the mechanical tests revealed that the LUCA graft exhibits significantly improved mechanical properties compared to the standalone autograft (mechanical strength of about 58N). Therefore, the LUCA graft is a great structural support for autograft (or xenograft and allograft) during ligament healing.
  • the 3-D braided scaffolds disclosed herein may be particularly useful as replacement constructs for the above-described exemplary ligaments and tendons, as well as any other ligaments or tendons which have been damaged, as these scaffolds arc degradable, porous, biocompatible, exhibit sufficient strength and promote formation of ligament and tendon tissue.
  • the fiber based design of the scaffold emulates the natural ligament or tendon and the braided structure offers mechanical strength as well as needed porosity for cell attachment and ingrowth.
  • the term “substantially” means to a great or significant extent, but not completely.
  • weight or amount as used herein with respect to the percent amount of an ingredient refers to the amount of the raw material comprising the ingredient, wherein the raw material may be described herein to comprise less than and up to 100% activity of the ingredient. Therefore, weight percent of an active in a composition is represented as the amount of raw material containing the active that is used and may or may not reflect the final percentage of the active, wherein the final percentage of the active is dependent on the weight percent of active in the raw material.
  • administering means the actual physical introduction of a composition into or onto (as appropriate) a subject, a host, or cell. Any and all methods of introducing the composition into the subject, host or cell are contemplated according to the invention; the method is not dependent on any particular means of introduction and is not to be so construed. Means of introduction are well-known to those skilled in the art, and also are exemplified herein. “Providing” means giving, administering, selling, distributing, transferring (for profit or not), manufacturing, compounding, or dispensing.
  • subject or “patient” is used herein to refer to an animal, such as a mammal, including a primate (such as a human, a non-human primate, e.g., a monkey, and a chimpanzee), a non-primate (such as a cow, a pig, a camel, a llama, a horse, a goat, a rabbit, a sheep, a hamster, a guinea pig, a cat, a dog, a rat, a mouse, and a whale), a bird (e.g., a duck or a goose), and a shark.
  • a primate such as a human, a non-human primate, e.g., a monkey, and a chimpanzee
  • a non-primate such as a cow, a pig, a camel, a llama, a horse, a goat, a rabbit, a sheep, a
  • the subject or patient is a human subject or a human patient, such as a human being treated or assessed for a disease, disorder or condition, a human at risk for a disease, disorder or condition, a human having a disease, disorder or condition, and/or human being treated for a disease, disorder or condition as described herein.
  • the subject is about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years of age.
  • the subject is about 5-10, 10-15, 15- 20, 20-25, 25-30, 30-35, 35-40, 40-45, 45-50, 50-55, 55-60, 60-65, 65-70, 70-75, 75-80, 80-85, 85-90, 90-95, 95-100 years of age.
  • a subject is “in need of treatment” if such subject would benefit biologically, medically, or in quality of life from such treatment.
  • a subject in need of treatment does not necessarily present symptoms, particular in the case of preventative or prophylaxis treatments.
  • the disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims are introduced into another claim.
  • any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim.
  • elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group.
  • isotopes include those atoms having the same atomic number but different mass numbers and encompass heavy isotopes and radioactive isotopes.
  • isotopes of hydrogen include tritium and deuterium
  • isotopes of carbon include n C, 13 C, and 14 C.
  • the compounds disclosed herein may include heavy or radioactive isotopes in the structure of the compounds or as substituents attached thereto. Examples of useful heavy or radioactive isotopes include 18 F, 15 N, 18 O, 76 Br, 125 I and 131 I.
  • a significant change is any detectable change that is statistically significant in a standard parametric test of statistical significance such as Student’s t-test, where p ⁇ 0.05.
  • any element expressed as a means for performing a specified function is intended to encompass any way of performing that function including, for example, a) a combination of circuit elements and associated hardware which perform that function or b) software in any form, including, therefore, firmware, microcode or the like as set forth herein, combined with appropriate circuitry for executing that software to perform the function.
  • the adjective “another,” when used to introduce an element, is intended to mean one or more elements.
  • the terms “including” and “having” are intended to be inclusive such that there may be additional elements other than the listed elements.
  • the term “exemplary” is not intended to be construed as a superlative example but merely one of many possible examples.
  • a synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; and a spacer positioned within the component to create a hollow space configured to receive a tissue graft.
  • a synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; a spacer positioned within the sleeve, wherein the spacer comprises either: a removable spacer configured to be removed to create a hollow space for receiving a tissue graft; or a biodegradable spacer configured to degrade in vivo after implantation; and a tissue graft configured to be received within the hollow space.
  • Clause 6 The synthetic scaffold of any one of clauses 4 or 5, wherein the hydrogel comprises fibrin gel, hyaluronic acid, or any combination thereof.
  • the expandable spacer comprises at least one of: an inflatable component configured to be expanded using a biocompatible fluid; or a mechanical expansion mechanism comprising at least one of a collapsible mesh structure or telescoping segments.
  • Clause 13 The synthetic scaffold device of clause 1, further comprising a tissue graft positioned within the hollow space, wherein the tissue graft comprises at least one of an autograft, an allograft, or a xenograft.
  • the biodegradable spacer comprises a material comprising poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), or combinations thereof.
  • PLLA poly-L-lactic acid
  • PLA poly(DL)-lactic acid
  • PGA polyglycolic acid
  • PLGA poly(lactic-co-glycolic acid)
  • tissue graft comprises at least one of a heterogeneous autograft, a bonc-patclla-bonc autograft, an Achilles allograft, or other tendon allograft or autograft such as quad tendon, or hamstring tendon.
  • a composite tissue scaffold comprising: a load-bearing scaffold structure formed from biodegradable polymers (braided, woven, knitted or any combination thereof); a temporary spacing element disposed within the load-bearing scaffold structure; and wherein the temporary spacing element maintains a tissue insertion channel during storage and transportation.
  • Clause 18 The synthetic scaffold of clause 6, wherein the sleeve comprises a component/s that is braided, woven, knitted or any combination thereof.
  • Clause 25 The synthetic scaffold of clause 24, wherein the sleeve comprises plurality of component layers wherein the component layer comprises a braided component, a woven component, a knitted component, or any combination thereof.
  • Clause 34 The composite tissue scaffold of clause 16, wherein the temporary spacing element is configured to be removed and replaced with biological tissue without damaging the load-bearing scaffold structure.
  • a method of making a synthetic scaffold device/system comprising: [0133] forming a sleeve comprising a component that is braided, woven, knitted or any combination thereof; positioning a spacer within the sleeve during formation to create a hollow space; and configuring the hollow space to receive a tissue graft; wherein the spacer comprises either a removable spacer configured to be removed before or during implantation, or a biodegradable spacer configured to degrade after implantation.
  • Clause 36 The method of clause 35, wherein when the spacer is biodegradable, the method further comprises selecting the biodegradable spacer to have a degradation rate coordinated with tissue healing timeline.
  • Clause 37 The method of clause 35, further comprising: removing the spacer when the spacer is removable; inserting a tissue graft into the hollow space; and implanting the synthetic scaffold device and tissue graft in a subject.
  • a method of ligament reconstruction comprising: providing a scaffold (braided, woven, knitted or any combination thereof) having a removable spacer disposed therein; preparing a tissue graft for implantation; removing the spacer from the scaffold to create an insertion pathway; inserting the tissue graft through the insertion pathway; and securing the scaffold containing the tissue graft to bone.
  • a method of manufacturing a tissue scaffold comprising: braiding, wowing, and/or knitting biodegradable fibers around a removable mandrel to form a sleeve; treating the sleeve and mandrel with a bioactive solution; drying the bioactive solution to form a coating; and maintaining the mandrel within the sleeve until time of use.
  • a method of preparing a tissue scaffold comprising: forming a polymer sleeve (braided, woven, knitted or any combination thereof) around a removable core; incorporating bioactive agents into the braided polymer sleeve; packaging the polymer sleeve with the removable core; and maintaining sterility of an inner lumen defined by the removable core.
  • Clause 41 The method of any one of clauses 35, 38, 39, or 40, further comprising incorporating a bioactive material into the synthetic scaffold device prior to implanting.
  • Clause 42 The method of clause 38, further comprising applying a bioactive material to at least one of the scaffolds or the tissue graft prior to securing the scaffold.
  • Clause 43 The method of clause 38, wherein securing comprises anchoring the scaffold within bone tunnels.
  • Clause 45 The method of clause 38, further comprising modifying the tissue graft with growth factors prior to insertion into the scaffold.
  • a system for soft tissue repair comprising: a biomaterial scaffold (braided, woven, knitted or any combination thereof) having a longitudinal axis; a removable core member extending along the longitudinal axis; and a bioactive material disposed between the biomaterial scaffold and the removable core member.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Textile Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Rehabilitation Therapy (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un échafaudage synthétique pour la régénération de ligament et de tissu mou qui combine une structure biodégradable tridimensionnelle avec un tube d'espacement amovible qui permet l'incorporation de tissu d'autogreffe, d'allogreffe ou de xénogreffe. La conception comprend un noyau creux créé par l'élément d'espacement, permettant une insertion facile de greffes tissulaires tout en fournissant un support structural à travers le composant tressé constitué d'acide poly-L-lactique (PLLA) et/ou d'acide poly (DL)-lactique (PLA). Dans un test de preuve de concept à l'aide d'un modèle de lapin, l'échafaudage a démontré des propriétés mécaniques supérieures par comparaison avec des autogreffes autonomes, avec des charges de pic d'environ 500N par rapport à 58N. Cette innovation aborde les limitations des techniques de reconstruction de ligament croisé antérieur (ACL) actuel en offrant un support mécanique amélioré et un environnement de cicatrisation biologique amélioré.
PCT/US2024/054050 2023-11-01 2024-11-01 Échafaudage synthétique et ses utilisations Pending WO2025096889A1 (fr)

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US20090082840A1 (en) * 2007-09-24 2009-03-26 Boston Scientific Scimed, Inc. Method for loading a stent into a delivery system
US20140309726A1 (en) * 2011-12-22 2014-10-16 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Biodegradable vascular grafts
US20140058496A1 (en) * 2012-08-21 2014-02-27 Regents Of The University Of Minnesota Decellularized biologically-engineered tubular grafts
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US20170246351A1 (en) * 2014-09-02 2017-08-31 Rutgers, The State University Of New Jersey Biocompatible Textile Sleeves to Support and Guide Muscle Regeneration and Methods of Use Thereof
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