Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation
Hydrogels comprising a macromolecular matrix and water may be used to augment soft tissue of a human being, promote or support cell or tissue viability or proliferation, create space in tissue, and for other purposes. A macromolecular matrix may comprise a hyaluronic acid component crosslinked to a collagen component.
1. A method of treating a soft tissue defect in a subject, the method comprising injecting a dermal filler composition into the subject's skin; wherein the composition comprises:
(i) a hydrogel comprising:
(a) water; and
(b) a crosslinked macromolecular matrix comprising hyaluronic acid crosslinked to collagen via a plurality of crosslink units, wherein at least a portion of the crosslink units comprise an amide bond, and wherein the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 7:1;
wherein said hydrogel has a hyaluronic acid concentration of 6 mg/mL to 21 mg/mL, a collagen concentration of 3 mg/mL to 12 mg/mL, and a storage modulus value of between 850 Pa and 5,000 Pa; and
(ii) a cellular component comprising cells obtained from adipose tissue;
wherein the composition has a fat:hydrogel weight ratio of 1:1 to 5:1; and
wherein the injection results in an increase in soft tissue volume and an increase in the volume retention, thereby treating the defect.
2. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using a coupling agent, and wherein the coupling agent is not part of the crosslink unit.
3. The method of claim 1 , wherein the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 2:1.
4. The method of claim 1 , wherein the hydrogel has a collagen concentration of greater than or equal to 6 mq/mL.
5. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of at least 9 mg/mL.
6. The method of claim 1 , wherein the hydrogel has a storage modulus value of between 1,000 Pa and 4,000 Pa.
7. The method of claim 1 , wherein the cellular component comprises adipocytes, adipose-derived stem cells, stromal vascular fraction cells, or a combination thereof.
8. The method of claim 1 , wherein the adipose tissue is human adipose tissue.
9. The method of claim 8 , wherein the adipose tissue is a lipoaspirate.
10. The method of claim 1 , wherein the adipose tissue comprises stem cells, progenitor cells, precursor cells or a combination thereof.
11. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using hyaluronic acid having a molecular weight of 1,000,000 to 5,000,000 daltons.
12. The method of claim 1 , wherein the defect is a wrinkle.
13. The method of claim 1 , wherein the increase in the volume retention is a fat graft volume retention.
14. The method of claim 1 , wherein the hydrogel has a collagen concentration of 6 mg/mL, 8 mg/mL or 12 mg/mL.
15. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 6 mg/mL; a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 12 mg/mL; or a hyaluronic acid concentration of 16 mg/mL and a collagen concentration of 8 mg/mL.
16. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using hyaluronic acid having a molecular weight of 1,000,000 daltons to 3,000,000 daltons.
17. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of at least 9 mg/mL and a collagen concentration of greater than or equal to 6 mg/mL.
18. The method of claim 1 , wherein the composition is injected intradermally.
19. The method of claim 1 , wherein the composition is injected subcutaneously.