Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation

Abstract

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.

What is claimed is: 
     
         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.