Preparation and/or formulation of proteins cross-linked with polysaccharides
Therapeutic compositions and/or formulations are provided, comprising: at least one cross-linked protein matrix, wherein the at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein.
1. A method of enhancing tissue in-growth and/or tissue re-growth in a patient in need thereof, comprising administering to the patient a tissue compatible composition comprising a cross-linked protein matrix, wherein the cross-linked protein matrix comprises:
i) a protein selected from the group consisting of tropoelastin and albumin;
ii) a hyaluronic acid cross-linking molecule comprising one or more carboxyl groups; and
iii) at least one intermolecular cross-linkage comprising an amide bond between an amine of the protein and a carboxyl group of the hyaluronic acid cross-linking molecule.
2. The method of claim 1 , wherein the tissue compatible composition is administered to the patient via injection, topically, or during surgery.
3. The method of claim 1 , wherein the tissue compatible composition is needle injectable, retains a coherent structure, and is sufficiently cross-linked to slow the composition's resorption in vivo.
4. The method of claim 2 , wherein the tissue compatible composition retains sufficient cohesiveness after needle extrusion such that strings of extruded composition do not break during extrusion.
5. The method of claim 1 , wherein the hyaluronic acid has one or more of the following properties: bioavailable, biodegradeable, bioabsorbable, or bioresorbable.
6. The method of claim 1 , wherein
the protein is tropoelastin.
7. The method of claim 1 , wherein the tissue compatible composition is administered to the patient in need thereof via injection.
8. The method of claim 7 , wherein the tissue compatible composition is extrudable through needles of 18G to 31G to a length of between about 5 cm to about 30 cm and the extruded composition holds together without surface support.
9. The method of claim 1 , wherein the tissue compatible composition is used to bulk, augment tissues or combinations thereof in at least one of the following: restorative surgery; dermatological surgery; eye surgery; plastic surgery; vascular surgery; reconstructive surgery; orthopedic surgery; for tissue augmentation; for supplementation of a body cavity or a deficit; or restoring volume effused during surgery.
10. The method of claim 1 , wherein the tissue compatible composition is administered to the patient in need thereof topically.
11. The method of claim 10 , wherein the tissue compatible composition is topically administered on healthy or injured tissue of the patient in need thereof in a cosmetological application or dermatological application.
12. The method of claim 10 , wherein the tissue compatible composition is topically administered on healthy or injured tissue of the patient in need thereof to fill facial wrinkles; fill fine lines; treat aging skin; treat scarred tissue; or treat skin depressions.
13. A method of enhancing tissue in-growth and/or tissue re-growth in a patient in need thereof, comprising administering to the patient a tissue compatible composition having a cross-linked protein matrix comprising
a protein selected from the group consisting of tropoelastin and albumin, and hyaluronic acid,
wherein the protein and hyaluronic acid are cross-linked by at least one amide bond formed between an amine of a residue from the protein and a carboxyl group from the hyaluronic acid.
14. The method of claim 13 , wherein the tissue compatible composition is administered to the patient via injection, topically, or during surgery.
15. The method of claim 13 , wherein the tissue compatible composition is needle injectable, retains a coherent structure, and is sufficiently cross-linked to slow the composition's resorption in vivo.
16. The method of claim 14 , wherein the tissue compatible composition retains sufficient cohesiveness after needle extrusion such that strings of extruded composition do not break during extrusion.
17. The method of claim 13 , wherein the hyaluronic acid has one or more of the following properties bioavailable, biodegradeable, bioabsorbable, or bioresorbable.
18. The method of claim 13 , wherein the protein is tropoelastin.
19. The method of claim 13 , wherein the tissue compatible composition is administered to the patient in need thereof via infection.
20. The method of claim 19 , wherein the tissue compatible composition is extrudable through needles of 18G to 31G to a length of between about 5 cm to about 30 cm and the extruded composition holds together without surface support.
21. The method of claim 13 , wherein the tissue compatible composition is used to bulk, augment tissues or combinations thereof in at least one of the following: restorative surgery; dermatological surgery; eye surgery; plastic surgery; vascular surgery; reconstructive surgery; orthopedic surgery; for tissue augmentation; for supplementation of a body cavity or a deficit; or restoring volume effused during surgery.
22. The method of claim 13 , wherein the tissue compatible composition is administered to the patient in need thereof topically.
23. The method of claim 22 , wherein the tissue compatible composition is topically administered on healthy or injured tissue of the patient in a cosmetological application or dermatological application.
24. The method of claim 22 , wherein the tissue compatible composition is topically administered on healthy or injured tissue of the patient in need thereof to fill facial wrinkles; fill fine lines; treat aging skin; treat scarred tissue; or treat skin depressions.