Implantable synthetic structures comprising porous polymers - Patents.com

Abstract

The present invention provides a synthetic structure comprising at least one porous polymer that is an implantable anatomical scaffold, such as an orthopedic scaffold, and provides a process for its manufacture and use in implantation into the human body.

Description

[Background technology]

[0001] Bone replacement and replacement of other anatomical structures have been known for the past century with various clinical applications, such as spinal fusion, high tibial osteotomy, long bone fractures, oral and maxillofacial surgery, and periodontal treatment. There are various bone substitute materials that have been used over the years, such as those derived from biological preparations, demineralized bone matrix, platelet-rich plasma, hydroxyapatite, growth factor additives (e.g. bone morphogenetic proteins), or synthetics like calcium sulfate, tricalcium phosphate ceramics, bioactive glasses, and polymer-based substitutes. All these substitute materials are not suitable for all clinical applications and need to be selected selectively depending on the purpose.

[0002] Damage or loss of articular cartilage is at the heart of a common problem encountered by orthopedic surgeons. This problem spans all age groups and can cause significant morbidity, negatively impacting function and quality of life. The treatment of cartilage and osteochondral lesions remains of great interest to orthopedic surgeons, as most lesions do not heal spontaneously and may induce the subsequent development of secondary osteoarthritis.

[0003] Focal cartilage defects are present in up to 63% of patients undergoing knee arthroscopy and may be more common in athletes. Although there are numerous surgical techniques aimed at cartilage repair, including microfracture, osteochondral allografts, osteochondral autograft transfer systems, and autologous chondrocyte implantation (ACI), these injuries present complex challenges. Microfracture has long been used as the primary technique to repair cartilage damage due to its ease of use and arthroscopic application. This repair allows patients to experience pain relief and regain function for a limited time, but the altered biomechanical and mechanical properties of fibrocartilage make it unable to tolerate repetitive loading of the articular surface. Microfracture has been shown to provide suboptimal results in athletes and elderly populations after a short period of pain relief, leading to gradual deterioration of the articular surface due to failure of the repair tissue and recurrence of arthritic symptoms.

[0004] The main limitations in the use of bone substitutes are the management of large defects and the lack of central vascularization, which may manifest itself later in their use.

[0005] For example, in cartilage repair techniques, there is a need to create an anatomical orthopedic scaffold that can restore normal function by regenerating hyaline cartilage into the defect while integrating this repair cartilage with native tissue. There is a need to create a scaffold that is cost-effective, time-efficient, single-stage, and can be used without cell-based techniques. Summary of the Invention

[0006] Thus, the present invention provides a synthetic structure comprising at least one porous polymer that is an implantable orthopedic scaffold.

[0007] Thus, the present invention provides a synthetic structure comprising at least one porous polymer that is an implantable synthetic anatomical scaffold.

[0008] Reference to an implantable (anatomical) structure should be understood to include a scaffold that is at least partially a counterpart of a corresponding anatomical structure in a subject (e.g., at least a portion of a limb, organ, skeleton, muscle, cartilage, etc.).

[0009] The implantable structures are used to be fixed, interconnected, joined, fused, or adhered to a portion of the human body of a subject in need thereof, thus providing the subject with the ability to resume the full function of the complete anatomical structure in which the implant is implanted. In some embodiments, the implantable synthetic anatomical structures of the present invention provide a reconstructed anatomical structure, or at least a portion thereof, that can be implanted in a subject in need thereof.

[0010] In some embodiments, the implantable synthetic anatomical scaffold is an orthopedic scaffold, hi some embodiments, the orthopedic scaffold is a scaffold that conforms, at least in part, to a corresponding orthopedic anatomy of a subject.

[0011] In some embodiments, the implantable structure is selected from bone-ligament connections, muscles, tendons, bone-bone connections, joints, joint capsules, synovial membranes, cartilage, and any combination thereof.

[0012] In some embodiments, the structure further comprises additional connection elements, such as, for example, screws, cable ties, metal plates, hooks, wires, or any other high torque connections.

[0013] In some embodiments, the orthopedic anatomical structure is an orthopedic anchor covered with a patch comprising at least one porous polymer.

[0014] In some other embodiments, the structure further comprises at least one soft tissue attachment surface adapted to be connected with a clamp, suture, or other type of connector to the polymeric porous material intended for gradual and permanent integration.

[0015] In some embodiments, the structure comprises a porous polymer structure having pores less than 5 microns, hi some embodiments, the structure comprises a porous polymer structure having pores between 5 and 20 microns.

[0016] In some embodiments, the structure is biocompatible, in some embodiments, the structure is biodegradable, in some embodiments, the structure is non-biodegradable.

[0017] In some embodiments, the porous polymer comprises nanofibers.

[0018] In some embodiments, the porous polymer comprises at least one porous electrospun polymer.

[0019] In some embodiments, the structure further comprises additional synthetic artificial structures (such as additional bone replacement structures, metal implants, reinforcing structures, etc.).

[0020] In some embodiments, the porous polymer structure is selected from the group consisting of aromatic polyurethane, polycarbonate, poly(DTE carbonate), polycaprolactone (PCL), polylactic acid (PLA), poly-L-lactic acid (PLLA), poly(DL-lactide-co-caprolactone), poly(ethylene-co-vinyl acetate), poly(methyl methacrylate), poly(propylene carbonate), poly(vinylidene fluoride), polyacrylonitrile, polycaprolactone, polycarbomethylsilane, polylactic acid, polystyrene. The polymer may comprise at least one polymer selected from polyvinylpyrrolidone, polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyvinyl chloride (PVC), hyaluronic acid (HA), chitosan, alginate, polyhydroxypyrrolidone and copolymers thereof, nylon 11, cellulose acetate, hydroxyapatite, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(DL-lactide), polycaprolactone, and poly(L-lactide), or any combination thereof.

[0021] In some embodiments, the structure further comprises at least one active agent.

[0022] In some embodiments, the at least one active agent is selected from a protein, collagen, fibronectin, or TGF-β2, heparin, a growth factor, an antibody, an antimetabolite, a chemotherapeutic agent, an anti-inflammatory agent, an antibiotic agent, an antimicrobial agent, and any combination thereof.

[0023] In some embodiments, said implantable synthetic anatomical structure is selected from a bone structure, a cartilage structure, a ligament, a tendon, and any combination thereof.

[0024] The present invention further provides a synthetic structure as disclosed hereinabove and below for use in the treatment of an orthopedic condition or disorder.

[0025] In some embodiments, the orthopedic condition or injury is selected from ligament rupture (partial or full thickness), anterior and / or posterior cruciate ligaments, Achilles tendon rupture, cartilage damage (leading to defects, especially in weight-bearing joints), muscle rupture or avulsion, rupture of the muscle-to-muscle connection, rupture of the muscle-ligament connection, rupture of the muscle / ligament complex-to-bone connection, and any combination thereof.

[0026] The present invention further provides a synthetic structure as disclosed hereinabove and below for use in ligament replacement and reconstruction.

[0027] The present invention further provides a composite structure as disclosed hereinabove and below for use in an orthopedic anchor.

[0028] The invention further provides a synthetic structure as disclosed hereinabove and below for use in bone attachment.

[0029] The present invention provides a synthetic structure as disclosed hereinabove and below for use in ligament replacement and reconstruction.

[0030] The present invention provides a synthetic structure as disclosed hereinabove and below for use in treating a disease, condition, or disorder of a ligament.

[0031] The present invention provides synthetic structures as disclosed hereinabove and hereinafter for use in replacing and reconstructing cartilage.The present invention provides synthetic structures as disclosed hereinabove and hereinafter for use in treating a cartilage disease, condition, or disorder.

[0032] The present invention provides a synthetic structure as disclosed hereinabove and below for use in tendon replacement and reconstruction.

[0033] The present invention provides a synthetic structure as disclosed hereinabove and below for use in the treatment of a disease, condition, or disorder of the tendon.

[0034] In some embodiments, said implantable synthetic anatomical structure further comprises at least one sensor.

[0035] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of the specification, however, the invention both as to organization and method of operation, together with its objects, features, and advantages, may best be understood by reference to the following detailed description when read in conjunction with the accompanying drawings. [Brief description of the drawings]

[0036] [Figure 1] Illustrative diagram of ligament reconstruction using the structure of the present invention. The black circles are locking holes for external attachment of the artificial ligament to the bone using screws, tacks, or any other fasteners. [Diagram 2] 2A-2E are diagrams of the cartilage repair structure of the present invention. [Figure 3A] FIG. 1 is an illustration of an anatomical tendon reconstruction. [Figure 3B] FIG. 1 illustrates one embodiment of a structure of the present invention. [Figure 4] 4A-4B. Porous sleeve for orthopedic anchor. 4A) Humeral head secured with anchor. B) Preliminary sleeve for orthopedic anchor. C) Orthopedic anchor.

[0037] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, dimensions of some elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention. Ligament replacement and reconstruction

[0039] A thin synthetic polymer band for ligament reconstruction.

[0040] The band is constructed so that the zone of the band passing through the bone tissue is porous, and the zone crossing the joint cavity is configured to not adhere to surrounding structures (intra-articular), and is either a wire or a smooth material.

[0041] The band must have sufficient tensile strength to withstand wear of the joint and may vary with the particular joint. For example, an anterior cruciate ligament replacement must withstand loads in excess of 2000 Newtons. "In young specimens, the linear stiffness (242 ± 28 N / mm) and maximum load (2160 ± 157 N) values ​​found when the femur-ACL-tibia complex was tested in anatomical orientation were higher than previously reported values ​​(Woo SL, Hollis JM, Adams DJ, Lyon RM, Takai S. Tensile properties of the human femur-anterior cruciate ligament-tibia complex. Effects of specimen age and orientation. Am J Sports Med. 1991 May-Jun;19(3):217-25. doi:10.1177 / 036354659101900303. PMID:1867330).

[0042] Ligament replacement requires two safety mechanisms: Safety mechanism No. 1 - a locking mechanism at the site of the externalized artificial ligament. Safety mechanism No. 2 - an intra-articular locking mechanism that connects the artificial ligament on both sides at the entrance to the joint cavity, which gives the joint mechanical strength and spatial stability to the intraosseous part until healing is complete and the porous material is fully integrated with the bone.

[0043] The purpose of both safety mechanisms is to (i) relieve pressure from the porous intrabony segment, (ii) allow healing with some movement of the joint but no movement of the intrabony segment, and (iii) prevent traumatic or gradual slippage of the artificial ligament.

[0044] In Figure 1 there is a schematic diagram of the ligament replacement of the present invention. Purple indicates the smooth segments and red indicates the porous segments. The position of locking mechanism No. 2 is indicated by a yellow star. The artificial ligament is made of polymer. The central segment is smooth and the peripheral segments are porous to allow tissue ingrowth. The reinforcing elements embedded in the ligament structure are wires (nitinol or any other alloy). The ligament further provides elastic properties. Cartilage repair

[0045] The majority of cartilage repair procedures are performed on the knee or ankle. Usually, the cartilage does not heal at all and is usually replaced by scar tissue called hyaline cartilage. The cartilage scaffold of the present invention is a soft tissue substitute intended to replace damaged cartilage in any joint cavity. Figures 2A-2E provide illustrations of an embodiment of a cartilage repair scaffold.

[0046] The scaffolds of the present invention are designed to be chondroconductive and / or osteoconductive, and are implanted as cell-free structures.

[0047] The porous material of the scaffold of the present invention is able to withstand bone shear and impact forces to span the defect and promote tissue growth.

[0048] In some embodiments, the scaffolds of the present invention are further impregnated with stem cells prior to implantation. In other embodiments, the scaffolds of the present invention can be optionally attached to bone and embedded into deep gaps. Tendon Repair Embodiments

[0049] An example of an Achilles tendon is provided in FIG.

[0050] Currently, simple suturing techniques are employed when attempting to repair a ruptured tendon. In some embodiments of the scaffold of the present invention, the structure is in the form of a sleeve with a porous matrix facing inward and a smooth texture to improve sliding on the outer surface.

[0051] FIG. 3B shows a bilayer device with a porous inner layer and a smooth outer layer. Marked suture holes (101) provide initial traction and immobility during the initial follow-up period. A central constriction (100) adds friction to the area to be repaired. On both sides of the sleeve, extensions are required to facilitate insertion of the muscle (102) and bone (103) attachment sites. FIG. 4A-4B show a porous sleeve for an orthopedic anchor. FIG. 4A shows the humeral head fixed with the anchor. FIG. 4B shows the sleeve of an orthopedic anchor of the present invention. FIG. 4C shows an orthopedic anchor without a sleeve of the present invention.

Claims

1. A composite structure comprising at least one porous polymer that is an implantable anatomical scaffold.

2. A composite structure comprising at least one porous polymer that is an implantable orthopedic scaffold.

3. 3. The composite structure of claim 1 or 2, having a porous polymer structure with interpore pores of less than 5 microns.

4. 3. The composite structure of claim 1 or 2, which has a porous polymer structure with pores between 5 and 20 microns.

5. The synthetic structure of any one of claims 1 to 4, wherein the porous polymer structure comprises nanofibers.

6. The composite structure of any one of claims 1 to 5, wherein the porous polymer structure comprises at least one porous electrospun polymer.

7. 7. The synthetic structure of any one of claims 1 to 6, further comprising a further synthetic artificial structure.

8. The porous polymer structure may be selected from the group consisting of aromatic polyurethane, polycarbonate, poly(DTE carbonate) polycaprolactone (PCL), polylactic acid (PLA), poly-L-lactic acid (PLLA), poly(DL-lactide-co-caprolactone), poly(ethylene-co-vinyl acetate) vinyl acetate, poly(methyl methacrylate), poly(propylene carbonate), poly(vinylidene fluoride), polyacrylonitrile, polycaprolactone, polycarbomethylsilane, polylactic acid, polystyrene, polyvinylpyrrolidone, poly 8. The synthetic structure of any one of claims 1 to 7, comprising at least one polymer selected from vinyl alcohol (PVA), polyethylene oxide (PEO), polyurethane, polyvinyl chloride (PVC), hyaluronic acid (HA), chitosan, alginate, polyhydroxypyrate and its copolymers, nylon 11, cellulose acetate, hydroxyapatite, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(DL-lactide), and poly(L-lactide), or any combination thereof.

9. The synthetic structure of any one of claims 1 to 8, further comprising at least one active agent.

10. 11. The synthetic structure of claim 10, wherein the at least one active agent is selected from a protein, collagen, fibronectin, or TGF-β2, heparin, a growth factor, an antibody, an antimetabolite, a chemotherapeutic agent, an anti-inflammatory agent, an antibiotic agent, an antimicrobial agent, and any combination thereof.

11. The composite structure of any one of claims 1 to 10, wherein the scaffold is selected from bone structures, cartilage, ligaments, tendons, and any combination thereof.

12. A synthetic structure according to any one of claims 1 to 11 for use in the treatment of an orthopedic condition or disorder.

13. 14. The composite structure of claim 13, wherein the orthopedic condition or injury is selected from ligament rupture, anterior and / or posterior cruciate ligament, Achilles tendon rupture, cartilage damage, muscle rupture or avulsion, rupture of a muscle-to-muscle connection, rupture of a muscle-to-ligament connection, rupture of a muscle / ligament complex-to-bone connection, and any combination thereof.

14. A composite structure according to any one of claims 1 to 13 for use in ligament replacement and reconstruction.

15. A composite structure according to any one of claims 1 to 14 for use in an orthopedic anchor.

16. A composite structure according to any one of claims 1 to 15 for use in bone attachment.

17. A synthetic structure according to any one of claims 1 to 16 for use in cartilage replacement and reconstruction.

18. A composite structure according to any one of claims 1 to 17 for use in tendon replacement and reconstruction.

19. The implantable synthetic anatomical structure further comprises at least one sensor.

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