Fully synthetic implantable multi-phased scaffold

• US 8,753,391 B2
• Filed: 08/12/2009
• Issued: 06/17/2014
• Est. Priority Date: 02/12/2007
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Lu, Helen H., Spalazzi, Jeffrey
• Primary Examiner(s): GHERBI, SUZETTE JAIME J
• Application Number:
  US12/583,072
• Publication Number:
  US 20100292791A1
• Time in Patent Office: 1,770 Days
• Field of Search: 623 1311- 132
• US Class Current: 623/13.11
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61F 2/0811 Fixation devices for tendons or ligaments
• CPC Class Codes: A61F 2002/0858 Fixation of tendon or ligament between anchor and bone, e.g. interference screws, wedges
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: B29C 67/04 Sintering combined with compression B29C43/00

Abstract

An implantable device is provided for soft-tissue or soft tissue-to-bone repair, fixation, augmentation, or replacement that includes a biomimetic and biodegradable nanofiber scaffold. Also provided is a fully synthetic implantable multiphased scaffold which includes, in a single continuous construct, a plurality of phases to mimic the natural anatomy of a tendon or ligament and their insertion sites. Also provided are scaffold apparatuses for musculoskeletal tissue engineering.

Claims

1. A fully synthetic implantable multi-phased scaffold comprising, in a single continuous construct, at least three phases wherein

a) exactly two of the at least three phases are end phases adjacent to exactly one other phase of the at least three phases,

b) every phase, amongst the at least three phases, which is not an end phase is adjacent to exactly two other phases of the at least three phases,

c) each of the two end phases comprises a material having a higher ceramic concentration than each phase, amongst the at least three phases, that is not an end phase;

and

d) at least one of the at least three phases comprises a polymer-ceramic composite in which the ceramic is dispersed in the polymer,

so as to mimic the natural anatomy of a tendon or a ligament.

2. The fully synthetic implantable multi-phased scaffold according to claim 1, wherein the composition of each phase is selected to promote growth and maintenance of soft tissue and/or soft tissue-to-bone interfaces.

3. The fully synthetic implantable multi-phased scaffold according to claim 1, which is biodegradable.

4. The fully synthetic implantable multi-phased scaffold according to claim 1, wherein the at least three phase comprises:

a) a first phase comprising for anchoring the scaffold to bone, comprising a body and first and second ends;

b) a second phase comprising microspheres or mesh and having a body and first and second ends, the first end of the second phase being disposed at, and contacting, the second end of the first phase,

c) a third phase comprising a synthetic graft material suitable for implantation into a mammal, the synthetic graft material being dimensioned to have a body with first and second ends, the first end of the third phase being disposed at, and contacting, the second end of the second phase,

d) a fourth phase comprising microspheres or mesh and having a body and first and second ends, the first end of the fourth phase being disposed at, and contacting, the second end of the third phase, and

e) a fifth phase, comprising a material suitable for anchoring the scaffold to bone, having a body and first and second ends, the first end of the fifth phase being disposed at, and contacting, the second end of the fourth phase.

5. The fully synthetic implantable multi-phased scaffold according to claim 4 further comprising a sixth phase disposed at the first end of the first phase, and a seventh phase disposed at the second end of the fifth phase, the sixth and the seventh phases comprising a material dimensioned and suitable for mechanical fixation of each respective fourth phase to bone.

6. The fully synthetic implantable multi-phased scaffold according to claim 4, wherein each phase is joined to adjacent phase or phases by sintering or solvent evaporation.

7. The fully synthetic implantable multi-phased scaffold according to claim 5, wherein each phase is joined to adjacent phase or phases by sintering or solvent evaporation.

8. The fully synthetic implantable multi-phased scaffold according to claim 4, wherein at least one of the second and the fourth phases is adapted to support growth and maintenance of bone.

9. The fully synthetic implantable multi-phased scaffold according to claim 8, wherein the at least one of the second and the fourth phases is seeded with at least one of osteoblasts, osteoblast-like cells, and stem cells.

10. The fully synthetic implantable multi-phased scaffold according to claim 4, wherein the third phase is seeded with at least one of fibroblasts, fibroblast-like cells, and stem cells.

11. The fully synthetic implantable multi-phased scaffold according to claim 4, wherein at least one of the second and the fourth phases is seeded with at least one of chondrocytes, fibroblasts, and stem cells.

12. The fully synthetic implantable multi-phased scaffold according to claim 4, wherein at least one of the first, second, third, fourth or fifth phases is imparted with a medicament selected from the group consisting of anti-infectives, antibiotics, bisphosphonate, hormones, analgesics, anti-inflammatory agents, growth factors, angiogenic factors, chemotherapeutic agents, anti-rejection agents, and RGD peptides.

13. The fully synthetic implantable multi-phased scaffold according to claim 12, wherein at least one of the first, second, third, fourth or fifth phases is imparted with one or more growth factors.

14. The fully synthetic implantable multi-phased scaffold according to claim 8, which is adapted use in ligament repair or replacement.

15. The fully synthetic implantable multi-phased scaffold according to claim 14, wherein the ligament is selected from the group consisting of anterior-cruciate ligaments, medial collateral ligaments, lateral collateral ligaments, posterior cruciate ligaments, cricothyroid ligaments, periodontal ligaments, anterior sacroiliac ligaments, posterior sacroiliac ligaments, sacrotuberous ligaments, inferior pubic ligaments, superior pubic ligaments, suspensory ligaments of the penis, suspensory ligaments of the breast, volar radiocarpal ligaments, dorsal radiocarpal ligaments, ulnar collateral ligaments, and radial collateral ligaments.

16. The fully synthetic implantable multi-phased scaffold according to claim 8, which is adapted for use in tendon repair or replacement.

17. The fully synthetic implantable multi-phased scaffold according to claim 16, wherein the tendon is selected from the group consisting of rotator cuff tendons, elbow tendons, wrist tendons, hamstring tendons, patellar tendons, ankle tendons, and foot tendons.

18. The fully synthetic implantable multi-phased scaffold according to claim 17, wherein the tendon is selected from the group consisting of the supra-spinatus tendon, the Achilles tendon, and the patellar tendon.

38. The fully synthetic implantable multi-phased scaffold of claim 1 comprising:

a) a first phase comprising polyglactin poly(lactide-co-glycolide) (PLGA) mesh;

b) a second phase sintered to the first phase, comprising poly(DL-lactide-co-glycolide) (PLAGA) microspheres; and

c) a third phase sintered to the second phase, comprising PLAGA and bioactive glass (BG) composite microspheres.

39. The fully synthetic implantable multi-phased scaffold of claim 1 comprising:

a) a first phase comprising PLAGA mesh;

b) a second phase sintered to the first phase, comprising PLAGA and bioactive glass (BG) composite microspheres; and

c) a third phase sintered to the second phase, comprising PLAGA and BG composite microspheres, wherein the BG concentration in the third phase is higher than that in the second phase.

40. The fully synthetic implantable multi-phased scaffold of claim 1 comprising:

a) a first phase comprising PLAGA microspheres;

b) a second phase sintered to the first phase, comprising PLAGA microspheres and PLAGA and BG composite microspheres; and

c) a third phase sintered to the second phase, comprising PLAGA and BG composite microspheres.

42. The synthetic implantable multi-phased scaffold of claim 1, comprising

a) a first phase comprising a first material suitable for anchoring the scaffold to bone, the first phase comprising a body and first and second ends;

b) a second phase adjacent to the first phase, the second phase comprising a second material different from the first material, the second phase having a body and first and second ends, and the first end of the second phase being joined to the second end of the first phase;

c) a third phase adjacent to the second phase, the third phase comprising a same material as the first material, and having a body with first and second ends, and the first end of the third phase being joined to the second end of the second phase.

43. The synthetic implantable multi-phased scaffold of claim 1, comprising

a) a first phase comprising a material suitable for anchoring the scaffold to bone, the first phase comprising a body and first and second ends;

b) a second phase adjacent to the first phase, the second phase comprising a second material different from the first material, and haying a body and first and second ends, and the first end of the second phase being joined to the second end of the first phase;

c) a third phase adjacent to the second phase, the third phase comprising third material different from the first material and the second material, and having a body with first and second ends, and the first end of the third phase being joined to the second end of the second phase;

d) a fourth phase adjacent to the third phase, the fourth phase comprising a same material as the second material, and having a body and first and second ends, and the first end of the fourth phase being joined to the second end of the third phase;

e) a fifth phase adjacent to the fourth phase, the fifth phase comprising a same material as the first material, and having a body and first and second ends, and the first end of the fifth phase being joined to the second end of the fourth phase.

44. The synthetic implantable multi-phased scaffold of claim 1, comprising a longitudinal axis running through a center of each phase of the at least three phases, wherein the scaffold is compositionally and/or geometrically symmetrical about a plane of symmetry which is perpendicular to the longitudinal axis of the scaffold.

19. A fully synthetic implantable multi-phased scaffold for ligament or tendon repair, comprising:

a) a first phase comprising a material suitable for anchoring the scaffold to bone, comprising a body and first and second ends;

b) a second phase comprising microspheres or mesh and having a body and first and second ends, the first end of the second phase being disposed at, and contacting, the second end of the first phase,

c) a third phase comprising a synthetic graft material suitable for implantation into a mammal, the synthetic graft material being dimensioned to have a body with first and second ends, the first end of the third phase being disposed at, and contacting, the second end of the second phase,

d) a fourth phase comprising microspheres or mesh and having a body and first and second ends, the first end of the fourth phase being disposed at, and contacting, the second end of the third phase, and

e) a fifth phase, comprising a material suitable for anchoring the scaffold to bone, having a body and first and second ends, the first end of the fifth phase being disposed at, and contacting, the second end of the fourth phase.

20. The fully synthetic implantable multi-phased scaffold of claim 19 further comprising a sixth phase disposed at the first end of the first phase, and a seventh phase disposed at the second end of the fifth phase, the sixth and the seventh phases comprising a material dimensioned and suitable for mechanical fixation of the sixth and the seventh phases to bone.

21. The fully synthetic implantable multi-phased scaffold of claim 19, wherein each phase is joined to adjacent phase or phases by sintering or solvent evaporation.

22. The fully synthetic implantable multi-phased scaffold of claim 20, wherein the each phase is joined to adjacent phase or phases by sintering or solvent evaporation.

23. The fully synthetic implantable multi-phased scaffold of claim 19, wherein the ligament is anterior cruciate ligament.

24. The fully synthetic implantable multi-phased scaffold of claim 19 wherein the third phase is selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, degradable polyurethanes, and biopolymers, and a blend of two or more of the preceding polymers.

25. The fully synthetic implantable multi-phased scaffold of claim 24, wherein the third phase is selected from the group consisting of poly(lactide-co-glycolide), poly(lactide) and poly(glycolide).

26. The fully synthetic implantable multi-phased scaffold of claim 19, wherein the microspheres are selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, and biopolymers, and a blend of two or more of the preceding polymers.

27. The fully synthetic implantable multi-phased scaffold of claim 26, wherein the polymer comprises at least one of poly(lactide-co-glycolide), poly(lactide) and poly(glycolide).

28. The fully synthetic implantable multi-phased scaffold of claim 27, wherein the polymer is poly(lactide-co-glycolide) (PLGA).

29. The fully synthetic implantable multi-phased scaffold of claim 19, wherein the mesh is selected from the group consisting of woven fibers, non-woven fibers, and nanofibers.

30. The fully synthetic implantable multi-phased scaffold of claim 19, wherein the first phase and the fifth phase are made from a polymer-ceramic composite.

31. The fully synthetic implantable multi-phased scaffold of claim 30, wherein the polymer is selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, and biopolymers, and a blend of two or more of the preceding polymers and the ceramic is selected from the group consisting of bioactive glass, calcium phosphate, hydroxyapatite, and beta tricalcium phosphate.

32. The fully synthetic implantable multi-phased scaffold of claim 31, wherein the polymer is poly(lactide-co-glycolide) (PLGA) and the ceramic is bioactive glass.

33. The fully synthetic implantable multi-phased scaffold of claim 20, wherein the sixth and the seventh phases are selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, degradable polyurethanes, and biopolymers, and a blend of two or more of the preceding polymers.

34. The fully synthetic implantable multi-phased scaffold of claim 33, wherein the sixth and the seventh phases are selected from the group consisting of poly(lactide-co-glycolide), poly(lactide) and poly(glycolide).

35. The fully synthetic implantable multi-phased scaffold of claim 19 further comprising a mesh disposed between adjacent phases.

36. The fully synthetic implantable multi-phased scaffold of claim 35, wherein the mesh is made from a material selected from the group consisting of woven fibers, non-woven fibers, and nanofibers.

37. The fully synthetic implantable multi-phased scaffold of claim 36, wherein the mesh is comprised of one or more layers.

41. A fully synthetic implantable scaffold comprising, in a single continuous construct:

a) a first phase comprising a first bioactive material having a first cross section perpendicular to a longitudinal axis of the implantable scaffold;

b) a second phase comprising a first polymer-ceramic composite, having a second cross section perpendicular to the longitudinal axis of the implantable scaffold, said second cross section being substantially identical to the first cross section in geometry;

c) a third phase comprising a second polymer-ceramic composite or a polymer, having a third cross section perpendicular to the longitudinal axis of the implantable scaffold, said third cross section being substantially identical to the second cross section in geometry;

d) a fourth phase comprising a third polymer-ceramic composite, having a fourth cross section perpendicular to the longitudinal axis of the implantable scaffold, said fourth cross section being substantially identical to the third cross section in geometry;

e) a fifth phase comprising a second bioactive material, having a fifth cross section perpendicular to the longitudinal axis of the implantable scaffold, said fifth cross section being substantially identical to the fourth cross section in geometry;

wherein the first through fifth phases are arranged such that the second phase is in between the first and third phase, the third phase is in between the second and the fourth phase, and the fourth phase is in between the third and the fifth phase.