OXYGEN SCAVENGING TISSUE GRAFT WITH ENHANCED REGENERATIVE CAPACITY AND METHOD OF MANUFACTURE THEREOF
The invention relates to a biocompatible, oxygen scavenging tissue graft for repair and regeneration of tissue injury. The oxygen scavenging tissue graft induces a transient, local hypoxic environment that induces the surrounding tissue to upregulate endogenous pro-angiogenic growth factors to enhance the regenerative capacity of the tissue graft and aid in the healing of the tissue injury once the graft is implanted into a host.
1 . An implant for repairing tissue injury comprising:
a tissue graft; and
a biocompatible oxygen scavenger.
2 . The implant of claim 1 , wherein the tissue graft is of a biological origin.
3 . The implant of claim 2 , wherein the tissue graft of the biological origin is selected from the group consisting of a cortical bone, a cancellous bone, a demineralized bone, a partially demineralized bone, a connective tissue, a tendon, a pericardium, dermis, a cornea, a dura matter, a fascia, a heart valve, a ligament, a capsular graft, cartilage, a collagen, a nerve, a placental tissue, and combinations thereof.
4 . The implant of claim 1 , wherein the tissue graft is of synthetic origin.
5 . The implant of claim 4 , wherein the tissue graft of synthetic origin is selected from the group consisting of a metal, a thermoplastic, an elastomer, a polymers, a mineral, an organic mineral, and combinations thereof
6 . The implant of claim 1 , wherein the biocompatible oxygen scavenger has been deoxygenated.
7 . The implant of claim 1 , wherein the biocompatible oxygen scavenger is of biological origin.
8 . The implant of claim 7 , wherein the biocompatible oxygen scavenger of biological origin is selected from the group consisting of a heme-based formulation, a hemoglobin-based formulation, and a myoglobin-based formulation.
9 . The implant of claim 1 , wherein the biocompatible oxygen scavenger is of synthetic origin.
10 . The implant of claim 9 , wherein the biocompatible oxygen scavenger of synthetic origin is a perfluorocarbon.
11 . The implant of claim 10 , wherein the perfluorocarbon is at least one of a perfluorooctyl bromide, a perfluorohexyl bromide, a perfluorooctane, a perfluoropentane, a perfluorohexane, a perfluorodecalin, a perfluorotributylamine, a salt of perfluorotributylamine, a perfluorotriisopropylamine, a salt of perfluorotriisopropylamine, a perfluoro-crown ether containing 12 crown ethers, a perfluoro-crown ether containing 15 crown ethers, and a perfluoro-crown ether containing 18 crown ethers.
12 . The implant of claim 1 , wherein the oxygen scavenger induces transient hypoxia in the tissue surrounding the implant upon implantation.
13 . The implant of claim 12 , wherein the transient hypoxia in the tissue surrounding the implant induces expression of pro-angiogenic growth factors in the tissue surrounding the implant.
14 . A method of preparing a composition for repairing tissue injury with enhanced regenerative capacity comprising combining a tissue graft with a biocompatible oxygen scavenger.
15 . The method of claim 14 , wherein the tissue graft is of a biological origin.
16 . The method of claim 15 , wherein the tissue graft of the biological origin is selected from the group consisting of a cortical bone, a cancellous bone, a demineralized bone, a partially demineralized bone, a connective tissue, a tendon, a pericardium, dermis, a cornea, a dura matter, fascia, a heart valve, a ligament, a capsular graft, a cartilage, collagen, a nerve, a placental tissue, and combinations thereof.
17 . The method of claim 14 , wherein the tissue graft is of a synthetic origin.
18 . The method of claim 17 , wherein the tissue graft of the synthetic origin is selected from the group consisting of a metal, a thermoplastic, an elastomer, a polymer, a mineral, an organic mineral, and combinations thereof
19 . The method of claim 14 , wherein the biocompatible oxygen scavenger is of a biological origin.
20 . The method of claim 19 , wherein the biocompatible oxygen scavenger of the biological origin is selected from the group consisting of a heme-based formulation, a hemoglobin-based formulation, and a myoglobin-based formulation.
21 . The method of claim 14 , wherein the biocompatible oxygen scavenger is of a synthetic origin.
22 . The method of claim 21 , wherein the biocompatible oxygen scavenger of the synthetic origin is a perfluorocarbon.
23 . The method of claim 22 , wherein the perfluorocarbon is at least one of perfluorooctyl bromide, perfluorohexyl bromide, perfluorooctane, perfluoropentane, perfluorohexane, perfluorodecalin, perfluorotributylamine, a salt of perfluorotributylamine, a perfluorotriisopropylamine, a salt of perfluorotriisopropylamine, a perfluoro-crown ether containing 12 crown ethers, a perfluoro-crown ether containing 15 crown ethers, and a perfluoro-crown ether containing 18 crown ethers.
24 . The method of claim 14 , wherein the biocompatible oxygen scavenger of the composition is deoxygenated.