Crosslinkable 3D printed biomaterial-based implants and methods of manufacture thereof
View Patent ↗The invention provides articles of 3D printed biomaterials with retained physical properties and biological activity and methods of using the articles. Furthermore, the invention provides manufacturing conditions to generate 3D printed biomaterials with highly preserved biological activity.
1. A biomaterial-based implant formed under a mild crosslinking condition wherein the mild crosslinking condition is selected from the group consisting of a visible light exposure, an ultraviolet exposure and combinations thereof, wherein at least one pre-implantation property selected from the group consisting of a cohesion, a shape, and a size of the biomaterial-based implants is within between about 60% to about 100% of the at least one preimplantation property for up to about five years following formation of the implant and wherein the biomaterial-based implant retains greater than 80% of at least one biological activity selected from the group consisting of an osteoconductivity, an osteoinductivity, a chondroinductivity, a cellular recruitment, and a cell differentiation, and wherein the biomaterial-based implant comprises between two layers and about 50,000 layers of the biomaterial, wherein the biomaterial comprises a bone and a polymer, wherein the polymer is a biocompatible polymer, a biodegradable polymer or a combination thereof.
2. The implant of claim 1 , wherein the biomaterial-based implant ranges in thickness from about 0.1 mm to 100 mm, ranges in length from about 5 mm to 50 cm, and ranges in width from about 5 mm to 50 cm.
3. The implant of claim 1 , wherein the biomaterial of the implant further comprises a material selected from the group consisting of a connective tissue, a tendon, a pericardium, a dermis, a cornea, a dura matter, a fascia, a heart valve, a ligament, a capsular graft, a cartilage, a collagen, a nerve, a placental tissue, and combinations thereof.
4. The implant of claim 1 , wherein the bone is at least one of a cortical bone, a cancellous bone, or a corticocancellous bone.
5. The implant of claim 1 , wherein the bone is at least one of a demineralized bone, a partially demineralized bone, or a fully mineralized bone.
6. The implant of claim 1 , wherein the biomaterial is combined with at least one of a crosslinkable material, an additive, a binder, and a solvent.
7. The implant of claim 1 , wherein the polymer is the biodegradable polymer and wherein the biodegradable polymer is selected from the group consisting of a crosslinkable polycaprolactones, a polyethylene glycols, a polyhydroxyalkanoates, a polyesteramides, a polylactides, a polyglycolides, a poly(lactide-co-glycolide)s, a polyorthoesters, a polyoxazolines, a polyurethanes, combinations, and crosslinkable derivatives thereof.
8. The implant of claim 1 , wherein the polymer is a biodegradable polymer and provides gradual release of at least one additive from the biomaterial-based implant following implantation.
9. A three-dimensional printed biomaterial-based implant formed under a mild crosslinking condition wherein the mild crosslinking condition is selected from the group consisting of a visible light exposure, an ultraviolet exposure and combinations thereof, and wherein the three-dimensional printed biomaterial-based implant is produced with a three-dimensional printer, comprising:
a biomaterial comprises a bone and further comprises at least one of a connective tissue, a tendon, a pericardium, a dermis, a cornea, a dura matter, a fascia, a heart valve, a ligament, a capsular graft, a cartilage, a collagen, a nerve, and a placental tissue;
a crosslinking material, wherein the crosslinkable material is selected from the group consisting of a biodegradable polymer, a biocompatible polymer, and combinations thereof;
a thickness of between about 0.1 mm to 100 mm;
a length of between about 5 mm to 50 cm;
a width of between about 5 mm to 50 cm;
at least 80% of at least one biological activity selected from the group consisting of an osteoconductivity, an osteoinductivity, an chondroinductivity, a cellular recruitment, and a cell differentiation; and
between 60% to about 100% of at least one pre-implantation property selected from the group consisting of a cohesion, a shape, and a size of the biomaterial-based implants, wherein the at least one preimplantation property is maintained for up to about five years following formation of the implant, and wherein the biomaterial-based implant comprises between two layers and about 50,000 layers of the biomaterial.
10. The implant of claim 9 , further comprising at least one of a native growth factor or an intrinsic growth factor.
11. The implant of claim 9 , wherein the bone is selected from the group consisting of a cortical bone, a cancellous bone, and a corticocancellous bone.
12. The implant of claim 9 , wherein the bone is a demineralized bone, a partially demineralized bone, a fully mineralized bone, or combinations thereof.
13. The implant of claim 9 , wherein the bone is at least partially demineralized and wherein a residual calcium content of the bone is less than or equal to about 8%.
14. The implant of claim 9 , wherein the crosslinking material is the biodegradable polymer selected from the group consisting of a polycaprolactone, a polyethylene glycol, a polyhydroxyalkanoate, a polyesteramide, a polylactide, a polyglycolide, a poly(lactide-co-glycolide), a polyorthoester, a polyoxazoline, a polyurethane, and copolymers thereof.
15. The implant of claim 9 , further comprising an additive, a binder, a solvent, or combinations thereof.
16. The implant of claim 9 , further comprising between about 0 wt. % to about 50 wt. % of an additive in the total weight of the biomaterial, wherein the additive is selected from the group consisting of a bioactive agent, a biocompatible mineral, and combinations thereof.
17. The implant of claim 16 , wherein the additive is the bioactive agent and selected from the group consisting of an antibiotic, an anti-infective agent, and combinations thereof.
18. The implant of claim 17 , wherein the bioactive agent is the anti-infective agent and is selected from the group consisting of a silver sulfadiazine, a chlorhexidine, a gentamicin, a tobramycin, a vancomycin, and combinations thereof.
19. The implant of claim 9 , further comprising at least one of a hormone, a growth factor, or a cell.
20. The implant of claim 9 , further comprising up to about 75 wt. % of a binding agent.
21. A three-dimensional printed biomaterial-based implant, comprising:
a biomaterial comprises a bone and further comprises at least one of a connective tissue, a tendon, a pericardium, a dermis, a cornea, a dura matter, a fascia, a heart valve, a ligament, a capsular graft, a cartilage, a collagen, a nerve, a placental tissue, and combinations thereof;
a crosslinking material, wherein the crosslinkable material is selected from the group consisting of a biodegradable polymer, a biocompatible polymer, and combinations thereof;
at least one of an additive, a hormone, or a binder; and
at least one of a native growth factor or an intrinsic growth factor;
wherein a thickness of the implant is between about 0.1 mm to 100 mm;
wherein a length of the implant is between about 5 mm to 50 cm;
wherein a width of the implant is between about 5 mm to 50 cm;
wherein at least 80% of at least one biological activity selected from the group consisting of an osteoconductivity, an osteoinductivity, a chondroinductivity, a cellular recruitment, and a cell differentiation;
wherein between 60% to about 100% of at least one pre-implantation property selected from the group consisting of a cohesion, a shape, and a size of the biomaterial-based implants, wherein the at least one preimplantation property is maintained for up to about five years following formation of the implant; and
wherein the biomaterial-based implant comprises between two layers and about 50,000 layers of the biomaterial.
22. The implant of claim 21 , wherein the crosslinking material is the biodegradable polymer selected from the group consisting of a polycaprolactone, a polyethylene glycol, a polyhydroxyalkanoate, a polyesteramide, a polylactide, a polyglycolide, a poly(lactide-co-glycolide), a polyorthoester, a polyoxazoline, a polyurethane, and copolymers thereof.
23. The implant of claim 21 , wherein the binder is selected from the group consisting of a binder polymer, a glue, a gum, a sugar, a cellulose ether, a resin and combinations thereof.