Injectable silk fibroin particles and uses thereof

Abstract

The inventions provided herein relate to compositions, methods, delivery devices and kits for repairing or augmenting a tissue in a subject. The compositions described herein are injectable such that they can be placed in a tissue to be treated with a minimally-invasive procedure (e.g., by injection) and/or be molded flexibly into a tissue void of any shape and/or size. In some embodiments, the composition described herein comprises a plurality of silk fibroin particles, which can retain their original volume within the tissue for a period of time. The compositions can be used as a filler to replace a tissue void, e.g., for tissue repair and/or augmentation, or as a scaffold to support tissue regeneration and/or reconstruction. In some embodiments, the compositions described herein can be used for soft tissue repair or augmentation.

1 .- 110 . (canceled) 
     
     
         111 . A composition comprising:
 dry porous silk fibroin particles, wherein:
 (i) the porosity is at least 70%; 
 (ii) the silk fibroin constitutes at least 30% of the total composition; and 
 (iii) the particles have a size of about 1 μm to about 1,000 μm. 
   
     
     
         112 . The composition of  claim 111 , wherein the composition is formulated for injection. 
     
     
         113 . The composition of  claim 112 , wherein the injection is subcutaneous. 
     
     
         114 . The composition of  claim 112 , wherein the injection is into a tissue site. 
     
     
         115 . The composition of  claim 113 , wherein the tissue site is a soft tissue site. 
     
     
         116 . The composition of  claim 113 , wherein the tissue site is a hard tissue site. 
     
     
         117 . The composition of  claim 115 , wherein the hard tissue site is bone tissue. 
     
     
         118 . The composition of  claim 111 , wherein the dry porous silk fibroin particles have a porosity of at least about 80% or at least about 90%. 
     
     
         119 . A method of repairing or augmenting a tissue site in a subject comprising injecting the composition of  claim 111 . 
     
     
         120 . The composition of  claim 111 , wherein the composition further comprises at least one active agent. 
     
     
         121 . The composition of  claim 120 , wherein the at least one active agent is or comprises at least one of a biologically active agent, a cosmetically active agent, a cell attachment agent, a contrast agent, or any combinations thereof. 
     
     
         122 . The composition of  claim 121 , wherein the biologically active agent is selected from the group consisting of: a therapeutic agent, an anesthetic, a cell growth factor, a peptide, a peptidomimetic, an antibody or a portion thereof, an antibody-like molecule, nucleic acid, a polysaccharide, and any combinations thereof. 
     
     
         123 . The composition of  claim 121 , wherein the cell attachment agent is selected from the group consisting of: hyaluronic acid, collagen, crosslinked hyaluronic acid/collagen, an integrin-binding molecule, chitosan, elastin, fibronectin, vitronectin, laminin, proteoglycans, any derivatives thereof, and any combinations thereof. 
     
     
         124 . The composition of  claim 121 , wherein the cosmetically active agent is selected from the group consisting of: an anti-aging agent, an anti-free radical agent, an anti-oxidant, a hydrating agent, a whitening agent, a colorant, a depigmenting agent, a sun-blocking agent, a muscle relaxant, and any combinations thereof. 
     
     
         125 . The composition of  claim 111 , wherein the dry porous silk fibroin particles exclude an amphiphilic peptide. 
     
     
         126 . The composition of  claim 125 , wherein the amphiphilic peptide comprises a RGD motif. 
     
     
         127 . The composition of  claim 111 , further comprising a dermal filler material. 
     
     
         128 . The composition of  claim 127 , wherein the dermal filler material is selected from the group consisting of poly(methyl methacrylate) microspheres, hydroxylapatite, poly(L-lactic acid), hyaluronic acid, collagen, and any combinations thereof. 
     
     
         129 . A delivery device comprising the composition of  claim 111 .