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 augmenting a breast of a human subject, the method comprising:
(i) injecting a hydrogel component into the breast, wherein the hydrogel component comprises:
(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, an ester bond or both; and the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 7:1;
wherein said hydrogel component has a hyaluronic acid concentration of 6 mg/mL to 21 mg/mL and a collagen concentration of 3 mg/mL to 12 mg/mL; and
(ii) administering a fat component to the breast of the subject, wherein the fat component contains adipose tissue, adipocytes, or both, and wherein the fat component has been explanted from the human subject;
thereby augmenting the breast of the human subject.
2 . The method of claim 1 , wherein the method increases the soft tissue volume of the breast.
3 . The method of claim 1 , wherein the method increases the fat volume of the breast.
4 . The method of claim 3 , wherein retention of the fat volume is increased as compared to administering the fat component alone.
5 . The method of claim 4 , wherein variability in the retained fat volume is reduced as compared to administering the fat component alone.
6 . The method of claim 1 , wherein the injection of the hydrogel component and the administration of the fat component is performed sequentially.
7 . The method of claim 6 , wherein the injection of the hydrogel component precedes the administration of the fat component.
8 . The method of claim 6 , wherein the administration of the fat component precedes the injection of the hydrogel component.
9 . The method of claim 1 , wherein the hydrogel component is premixed with the fat component to provide a single composition, and the single composition is injected into the breast of the subject.
10 . The method of claim 1 , wherein the hydrogel is injected intradermally.
11 . The method of claim 1 , wherein the hydrogel is injected subcutaneously.
12 . The method of claim 1 , wherein the fat component is harvested from a donor site of the subject via a lipectomy procedure or a liposuction procedure.
13 . The method of claim 12 , wherein the fat component harvested from the donor site is obtained via a liposuction procedure and separated from blood, serum, proteases, lipases, tumescent fluid, or a combination thereof prior to the administration to the breast.
14 . The method of claim 12 , wherein the donor site is selected from the group consisting of a mammary region, an abdominal region, a thigh region, a flank region, a gluteal region, a trochanter region, or a gonadal region of the subject.
15 . The method of claim 12 , wherein the donor site is a buttock, a lateral thigh or a medial thigh.
16 . The method of claim 1 , wherein adipocyte proliferation is enhanced as compared to administering adipocytes alone.
17 . The method of claim 1 , wherein adipose tissue growth is enhanced as compared to administering adipose tissue alone.
18 . The method of claim 1 , wherein the method improves an aesthetic quality of the breast.
19 . The method of claim 18 , wherein the aesthetic quality is appearance.
20 . The method of claim 18 , wherein the aesthetic quality is tactile sensation.
21 . The method of claim 1 , wherein the human subject presents with breast hypoplasia prior to the augmentation.
22 . The method of claim 1 , wherein the human subject presents with tuberous breast deformity prior to the augmentation.
23 . The method of claim 1 , wherein the augmenting further comprises correcting a congenital anomaly, an acquired defect or a cosmetic defect.
24 . The method of claim 23 , wherein the congenital anomaly is unilateral mammary hypoplasia.
25 . The method of claim 23 , wherein the acquired defect is a depressed scar, a subcutaneous atrophy or a keratotic lesion.
26 . The method of claim 9 , wherein the single composition has a fat:hydrogel weight ratio of 1:1 to 5:1.
27 . The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using a coupling agent which is not part of the crosslink unit.
28 . The method of claim 1 , wherein the hydrogel component has a storage modulus value of between 850 Pa and 5,000 Pa.
29 . 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.
30 . The method of claim 1 , wherein the hydrogel component has a collagen concentration of greater than or equal to 6 mg/m L.
31 . The method of claim 1 , wherein the hydrogel component has a hyaluronic acid concentration of at least 9 mg/mL.
32 . The method of claim 1 , wherein the hydrogel component has a collagen concentration of 6 mg/mL, 8 mg/mL or 12 mg/mL.
33 . The method of claim 1 , wherein the hydrogel component has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 6 mg/mL.
34 . The method of claim 1 , wherein the hydrogel component has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 12 mg/mL.
35 . The method of claim 1 , wherein the hydrogel component has a hyaluronic acid concentration of 16 mg/mL and a collagen concentration of 8 mg/mL.
36 . The method of claim 1 , wherein the hydrogel component has a hyaluronic acid concentration of at least 9 mg/mL and a collagen concentration of greater than or equal to 6 mg/m L.
37 . 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.
38 . 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.
39 . The method of claim 1 , wherein the collagen is porcine collagen type I.
40 . The method of claim 1 , wherein the collagen is human collagen type I.