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 method for repairing or augmenting a tissue in a subject, the method comprising:
 injecting a composition in the tissue to be repaired or augmented, the composition comprising a plurality of silk fibroin particles and an injection carrier,   wherein at least a portion of the silk fibroin particles retain at least 50% of their original volume within the tissue for at least 6 weeks, and   wherein the silk fibroin particles have (i) a porosity of at least 70%, (ii) have a size from 1 μm to 2,000 μm, and (iii) a pore size from 10 nm to 1000 μm.   
     
     
         112 . The method of  claim 111 , wherein the silk fibroin particles are fabricated by forming a solid-state silk fibroin from a silk solution consisting of 4% (w/v) to 20% (w/v) silk fibroin and water, and by reducing the solid-state silk fibroin into particles. 
     
     
         113 . The method of  claim 111 , wherein the composition further comprises a hydrogel distributed within the silk fibroin particles. 
     
     
         114 . The method of  claim 111 , wherein reducing the solid-state silk fibroin particles is performed by a mechanical means selected from the group consisting of micronizing, milling, pulverizing, crushing, grinding, cutting, and any combinations thereof. 
     
     
         115 . The method of  claim 111 , wherein the solid-state silk fibroin formed by freeze-drying the silk solution. 
     
     
         116 . The method of  claim 111 , wherein at least a portion of the silk fibroin particles retain at least 70% of their original volume within the tissue for at least 6 weeks. 
     
     
         117 . The method of  claim 111 , wherein at least a portion of the silk fibroin particles retain at least 50% of their original volume within the tissue for at least 3 months. 
     
     
         118 . The method of  claim 111 , wherein at least a portion of the silk fibroin particles are adapted to degrade no more than 50% of their original volume in at least 3 months. 
     
     
         119 . The method of  claim 111 , wherein the silk fibroin is mixed with a biocompatible polymer to form mixed polymer particles, wherein the biocompatible polymer comprises polycaprolactone. 
     
     
         120 . The method of  claim 111 , wherein the composition comprises at least one active agent. 
     
     
         121 . The method of  claim 120 , wherein the active agent is an anesthetic. 
     
     
         122 . The method of  claim 111 , wherein the composition comprises hyaluronic acid. 
     
     
         123 . The method of  claim 111 , wherein the composition further comprises a dermal filler. 
     
     
         124 . The method of  claim 123 , wherein the dermal filler is selected from the group consisting of poly(methyl methacrylate) microspheres, hydroxylapatite, poly(L-lactic acid), hyaluronic acid, collagen, and any combinations thereof. 
     
     
         125 . The method of  claim 111 , wherein the injection is performed subcutaneously, submuscularly, or intramuscularly. 
     
     
         126 . The method of  claim 111 , wherein the tissue is a soft tissue. 
     
     
         127 . The method of  claim 126 , wherein the soft tissue is selected from the group consisting of a tendon, a ligament, skin, a breast tissue, a fibrous tissue, a connective tissue, a muscle, and any combinations thereof. 
     
     
         128 . The method of  claim 111 , wherein the silk fibroin particles have a size from 10 μm to 1500 μm. 
     
     
         129 . The method of  claim 111 , wherein the pores have a size from 1 μm to 1000 μm. 
     
     
         130 . The method of  claim 111 , wherein the injection carrier comprises a saline solution.