Fibrin composition, method and wound articles
A method of forming a fibrin hydrogel composition is described. The method comprises forming an aqueous solution comprising fibrinogen, fibrin-forming enzyme, and a fibrin hydrogel forming salt. The fibrin hydrogel forming salt concentration is greater than or equal to the threshold concentration to form a fibrin hydrogel. The method further comprises reducing the salt concentration below the threshold concentration to form a fibrin hydrogel. In some embodiments, the aqueous solution further comprises a plasticizer. A fibrin composition is also described comprising a fibrin hydrogel having a fibrin concentration ranging from 0.1 to 10 wt-%; and a fibrin hydrogel forming salt. The fibrin hydrogel forming salt has a concentration less than a threshold concentration to form the fibrin hydrogel. The fibrin hydrogel or dehydrated fibrin hydrogel can be in various physical forms such a sheet, foam, or plurality of pieces. Also described are methods of forming a fibrin article, wound dressings and a method of treatment of a wound.
1. A method of forming a fibrin hydrogel composition comprising
forming an aqueous solution comprising fibrinogen, fibrin-forming enzyme, and a fibrin hydrogel forming salt; wherein the fibrin hydrogel forming salt has a concentration greater than or equal to the threshold concentration to form a fibrin hydrogel;
reducing the salt concentration below the threshold concentration to form a fibrin hydrogel.
2. The method of claim 1 wherein the fibrin hydrogel forming salt comprises calcium salt.
3. The method of claim 1 wherein the threshold concentration of the aqueous solution is at least 0.45 wt %.
4. The method of claim 1 wherein the aqueous solution further comprises a plasticizer.
5. The method of claim 4 wherein the plasticizer comprises a sugar alcohol, an alkane diol, or a combination thereof.
6. The method of claim 1 wherein the solution further comprises a buffering agent.
7. The method of claim 1 further comprising forming the fibrin hydrogel into a sheet, foam, or a plurality of pieces.
8. The method of claim 1 wherein the step of reducing the fibrin hydrogel forming salt concentration comprising rinsing the hydrogel with an aqueous solution.
9. The method of claim 1 further comprising dehydrating the fibrin hydrogel after reducing the salt concentration.
10. The method of claim 9 wherein the dehydrating comprises freeze-drying, oven drying, or combination thereof.
11. The method of claim 1 wherein the dehydrated fibrin hydrogel has a salt concentration no greater than 20 wt-% for a water content no greater than 20 wt-%.
12. The method of claim 9 further comprises forming the dehydrated hydrogel into a plurality of pieces.
13. A fibrin hydrogel composition prepared by the method of claim 1 .
14. A fibrin composition comprising
a fibrin hydrogel having a fibrin concentration ranging from 0.1 to 10 wt-%; and
fibrin hydrogel forming salt; wherein the fibrin hydrogel forming salt has a concentration less than a threshold concentration to form the fibrin hydrogel.
15. The fibrin composition of claim 14 wherein the fibrin hydrogel forming salt concentration is less than 0.45 10 wt-% of the hydrogel.
16. The fibrin composition of claim 14 wherein the fibrin hydrogel forming salt comprises calcium salt.
17. The fibrin composition of claim 14 wherein the fibrin hydrogel further comprises a plasticizer.
18. The fibrin composition of claim 16 wherein the plasticizer comprises a sugar alcohol, an alkane diol, or a combination thereof.
19. The fibrin composition of claim 18 wherein the fibrin hydrogel is at least partially dehydrated.
20. The fibrin composition of claim 19 wherein the dehydrated fibrin hydrogel has a salt concentration no greater than 20 wt-% for a water content no greater than 20 wt-%.
21. The fibrin composition of claim 14 wherein the fibrin hydrogel or dehydrated fibrin hydrogel in the form of a sheet, foam, or plurality of pieces.
22. A method of forming a fibrin article comprising providing a fibrin composition of claim 14 and disposing the fibrin composition on or within a carrier.
23. The method of claim 22 wherein the carrier is a skin adhesive, a release liner, a polymeric film, a polymeric foam, or a nonwoven or woven fibrous material.
24. The method of claim 22 further comprising sterilizing the fibrin composition using irradiation.
25. A wound dressing comprising a fibrin composition of claim 14 .
26. The wound dressing of claim 25 wherein the fibrin composition is disposed on or within a carrier.
27. The wound dressing of claim 26 wherein the carrier is selected from a skin adhesive, a release liner, a polymeric film, a polymeric foam, or a nonwoven or woven fibrous material.
28. The wound dressing of claim 25 wherein the fibrin composition is in the form of a sheet having a basis weight of 2 to 30 mg/cm 2 .
29. The wound dressing of claim 28 wherein the sheet has a thickness ranging from 10 μm to 200 μm.
30. A method of treatment of a wound comprising providing the fibrin composition of claim 14 proximate a wound.
31. The method of claim 30 wherein the fibrin composition increases the rate of re-epithelialization.
32. The method of claim 30 wherein the fibrin composition increases at least one wound healing biological marker selected from VEGF, EGF, MMP1, MMP8, MMP9, TIMP-1, and combination thereof.