Functionalized tissue matrices
View Patent ↗Disclosed herein are tissue treatment products that have been bound to at least one chelating agent. Also disclosed are tissue treatment products that have been functionalized with at least one metal and/or at least one metal-binding protein. The tissue treatment products can have antimicrobial properties and/or factors that promote or enhance native cell migration, proliferation, and/or revascularization after implantation into a subject. Also disclosed are methods of making and using the tissue treatment products. The tissue treatment products can be implanted into a tissue in need of repair, regeneration, healing, treatment, and/or alteration and can promote or enhance native cell migration, proliferation, and/or revascularization.
1. A tissue treatment product for inhibiting growth of S. aureus comprising:
a porous material comprising a natural or artificial scaffold, wherein the porous material comprises at least one of an extracellular matrix of a partially decellularized tissue, an extracellular matrix of a completely decellularized tissue, and a porous synthetic scaffold material, wherein the extracellular matrix of a partially or completely decellularized tissue is selected from at least one of human, nonhuman primate, pig, cow, horse, goat, sheep, dog, cat, rabbit, guinea pig, gerbil, hamster, rat, and mouse tissue;
at least one chelating agent selected from the group consisting of iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), or diethylenetriaminepentaacetic acid (DTPA) covalently bound to the porous material; and
zinc bound to the chelating agent(s) on the tissue treatment product.
2. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises a porous synthetic scaffold material.
3. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises at least one of a hyaluronic acid derivative, chitosan, polycaprolactone, polyglycolide, polylactide, polydioxane, a polyether ester, poly(lactide-co-glycolide), or polyhydroxyalkonate.
4. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises a polyurethane material.
5. The tissue treatment product of claim 1 , wherein the extracellular matrix is partially or completely decellularized pig tissue.
6. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises the extracellular matrix of partially or completely decellularized tissue selected from at least one of bone, skin, dermis, intestine, vascular, urinary bladder, tendon, ligament, muscle, fascia, neurologic tissue, vessel, liver, heart, lung, kidney, and cartilage tissue.
7. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises an extracellular matrix from one or more animal or tissue sources.
8. The tissue treatment product of claim 1 , wherein the tissue treatment product lacks substantially all alpha-galactose moieties.
9. The tissue treatment product of claim 1 , further comprising one or more viable cells.
10. The tissue treatment product of claim 9 , wherein the one or more cells are mammalian cells.
11. The tissue treatment product of claim 9 , wherein the one or more cells are stem cells.
12. The tissue treatment product of claim 1 , further comprising at least one factor selected from an anti-inflammatory agent, an analgesic, a cell growth factor, an angiogenic factor, a differentiation factor, a cytokine, a hormone, and a chemokine.
13. The tissue treatment product of claim 12 , wherein the at least one factor is encoded by a nucleic acid sequence contained within an expression vector.
14. The tissue treatment product of claim 13 , wherein the expression vector is contained within one or more viable cells.
15. The tissue treatment product of claim 1 , wherein the tissue treatment product has a reduced bioburden or substantially lacks all bioburden.
16. The tissue treatment product of claim 1 , wherein the at least one chelating agent is covalently bound to free amine, thiol, or hydroxyl groups on the porous material in the tissue treatment product.
17. The tissue treatment product of claim 1 , wherein the at least one chelating agent is covalently bound to the porous material in the tissue treatment product via an activating agent.
18. The method of claim 17 , wherein the activating agent is N-hydroxysulfosuccinimide (NHS), suberic acid bis(N-hydroxysuccinimide ester), 1,4-butanediol diglycidyl ether, epibromohydrin, or 1,2,7,8-diepoxyoctane.
19. The tissue treatment product of claim 1 , wherein the chelating agent comprises IDA.
20. The tissue treatment product of claim 1 , further comprising at least one metal in addition to zinc.
21. The tissue treatment product of claim 1 , wherein the tissue treatment product is further functionalized with at least one metal-binding protein.
22. The tissue treatment product of claim 21 , wherein the metal-binding protein has antimicrobial properties.
23. The tissue treatment product of claim 21 , wherein the metal-binding protein comprises lysostaphin.
24. The tissue treatment product of claim 21 , wherein the metal-binding protein comprises at least one matrix metalloproteinase.
25. The tissue treatment product of claim 24 , wherein the matrix metalloproteinase comprises a collagenase, gelatinase, stromolysin, matrilysin, or elastase.
26. The tissue treatment product of claim 1 , wherein the tissue treatment product comprises a porous material covalently bound to IDA and functionalized with zinc and lysostaphin.
27. A kit comprising the tissue treatment product of claim 1 and instructions for using the kit.
28. The kit of claim 27 , wherein the kit is packaged under aseptic or sterile conditions.