Rna based biomaterial for tissue engineering applications

Abstract

The present disclosure provides compositions and methods useful for tissue engineering including a composition having chemically modified RNA (cmRNA) encapsulated in or complexed with a non-viral delivery vehicle and a biocompatible, bioresorbable scaffold and methods of using the composition to regenerate, for example, bone tissue.

1 . A composition comprising chemically modified RNA (cmRNA) encapsulated in or complexed with a non-viral delivery vehicle and a biocompatible, bioresorbable scaffold. 
     
     
         2 . The composition of  claim 1  wherein the cmRNA encodes a protein that enhances cartilage regeneration, enhances bone regeneration, enhances ligament regeneration, enhances tendon regeneration, or enhances repair of cardiac, liver, bladder or muscle tissue. 
     
     
         3 . The composition of  claim 1  wherein the delivery vehicle comprises microparticles or nanoparticles. 
     
     
         4 . The composition of  claim 1  wherein the delivery vehicle comprises cationic or non-cationic polymers. 
     
     
         5 . The composition of  claim 4  wherein the delivery vehicle comprises PEI, chitosan, cyclodextrin or dendrimers. 
     
     
         6 . The composition of  claim 4  wherein the delivery vehicle comprises cationic liposomes or cationic emulsions. 
     
     
         7 . The composition of  claim 1  wherein the delivery vehicle comprises a synthetic polymer. 
     
     
         8 . The composition of  claim 7  wherein the synthetic polymer comprises PEI, PLGA, PLA, or PAMAM. 
     
     
         9 . The composition of  claim 8  wherein the PEI comprises branched PEI. 
     
     
         10 . The composition of  claim 1  wherein the delivery vehicle comprises complexes of cmRNA and the non-viral delivery vehicle that are encapsulated in a synthetic polymer. 
     
     
         11 . The composition of  claim 1  wherein the cmRNA encodes at least one of BMPs, osteocalcin, type I collagen, core binding factor, VEGF, PDGF, IGFI, IGFII, TGF-beta, antibody to sclerostin or the antigen binding fragment thereof, or antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) or the antigen binding fragment thereof, or osterix or at least one of HGF, TNF-alpha, IL6, bFGF, IGFII, NGF, neuregulin, or activin. 
     
     
         12 . The composition of  claim 1  wherein the scaffold comprises a natural polymer. 
     
     
         13 . The composition of  claim 12  wherein the natural polymer comprises collagen, proteoglycan, alginate, chitosan or extracellular matrix. 
     
     
         14 . The composition of  claim 1  wherein the scaffold comprises a synthetic polymer. 
     
     
         15 . The composition of  claim 14  wherein the synthetic polymer comprises PLA, PGLA, PLLA or polystyrene. 
     
     
         16 . The composition of  claim 1  wherein the cmRNA comprises 5-methylcytidine-5′-triphosphate, pseudoundine-5′-triphosphate, or combinations thereof. 
     
     
         17 . A method to enhance tissue regeneration in vivo comprising administering an effective amount of the composition of  claim 1  to a tissue of a mammal in need thereof. 
     
     
         18 . The method of  claim 17  wherein the tissue is bone. 
     
     
         19 . The method of  claim 17  wherein the composition is administered to a bone defect in the mammal or introduced to the jaw of the mammal. 
     
     
         20 . A method to enhance tissue regeneration ex vivo comprising introducing an effective amount of the composition of  claim 1  to cells of a mammal.