Pepsinized collagen implants and biomedical uses thereof
View Patent ↗Disclosed are pepsinized collagen implants, such as membranes and sponges, and methods of making them, which entails solubilizing pepsinized collagen in a buffer containing a polyol, e.g., mannitol or sorbitol, wherein the buffer has a substantially neutral pH. Methods of using the pepsinized collagen implants for clinical applications are also disclosed.
1. A method of preparing a collagen implant for use in tissue repair, comprising:
(a) digesting collagen with pepsin, thus producing pepsinized collagen;
(b) solubilizing the pepsinized collagen in a buffer composition comprising a polyol, wherein the buffer has a substantially neutral pH;
(c) drying the thus-solubilized, pepsinized collagen; and optionally
(d) reacting the collagen of (c) with a cross-linking agent, thus producing the collagen implant.
2. The method of claim 1 , wherein the collagen is present in the buffer composition in an amount of about 2 mg to about 20 mg per ml of the buffer.
3. The method of claim 1 , wherein the pH of the buffer composition is from about 6 to about 7.5.
4. The method of claim 1 , wherein the polyol is present in the buffer composition in a concentration of about 5% to about 10% (w/v).
5. The method of claim 1 , wherein the polyol is sorbitol.
6. The method of claim 1 , wherein the polyol is mannitol.
7. The method of claim 1 , further comprising adding Type-I collagen fibers to the buffer composition prior to drying.
8. The method of claim 7 , wherein the Type-I collagen fibers and the pepsinized collagen are present in the buffer composition in a weight ratio of about 1:5 to about 1:2.
9. The method of claim 1 , further comprising adding an anti-adhesive agent to the buffer composition prior to the drying.
10. The method of claim 9 , wherein the anti-adhesive agent includes glucuronic acid, glucosamine, or a combination thereof.
11. The method of claim 9 , wherein the anti-adhesive agent includes succinic anhydride.
12. The method of claim 9 , wherein the anti-adhesive agent includes bis(3-aminopropyl)polyethylene glycol having an average molecular weight (Mn) of about 1500.
13. The method of claim 9 , wherein the anti-adhesive agent includes poly(ethylene glycol)bis(carboxymethyl)ether having a Mn of about 600.
14. The method of claim 9 , further comprising adding to the buffer composition, or to the formed implant, at least one therapeutically active or beneficial agent selected from the group consisting of antibiotics, analgesics, anti-inflammatory agents, cells, growth factors, and combinations of two or more thereof.
15. The method of claim 1 , wherein the drying comprises lyophilization.
16. The method of claim 9 , wherein the drying comprises air drying.
17. The method of claim 1 , wherein the cross-linking agent comprises 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), glutaraldehyde, or genipin.
18. The method of claim 17 , wherein the cross-linking agent is added to the solubilized, pepsinized collagen in a concentration of about 0.1% to about 6% (w/v).