Biodegradable scaffolds

Abstract

In some embodiments, the present invention provides compositions that comprise: (1) a biodegradable polymer matrix; and (2) at least one biodegradable reinforcing particle that is dispersed in the matrix. In some embodiments, the biodegradable reinforcing particle is selected from the group consisting of porous oxide particles and porous semiconductor particles. In additional embodiments, the compositions of the present invention further comprise a (3) porogen particle that is also dispersed in the matrix. In further embodiments, the compositions of the present invention are also associated with one or more active agents. In various embodiments, the active agents are associated with the biodegradable polymer matrix, the biodegradable reinforcing particle, and/or the porogen particle. In various embodiments, the compositions of the present invention may be utilized as scaffolds, such as scaffolds for treating bone defects. Further embodiments of the present invention pertain to methods of making the compositions of the present invention.

What is claimed is: 
     
         1 . A composition comprising:
 (a) a biodegradable matrix comprised of at least one unsaturated polymer; and   (b) at least one biodegradable reinforcing particle dispersed in the matrix, wherein the at least one biodegradable reinforcing particle is selected from the group consisting of porous oxide particles and porous semiconductor particles.   
     
     
         2 . The composition of  claim 1 , wherein the biodegradable matrix comprises an unsaturated biodegradable polymer. 
     
     
         3 . The composition of  claim 2 , wherein the at least one unsaturated polymer comprises poly(propylene fumarate) (PPF). 
     
     
         4 . The composition of  claim 1 , further comprising hydrogel porogen particles, dispersed within the biodegradable matrix. 
     
     
         5 . The composition of  claim 4 , wherein the hydrogel porogen particles comprise at least one of alginates, fibrins, gelatins, and poly(lactic-co-glycolic acid) (PLGA). 
     
     
         6 . The composition of  claim 1 , further comprising at least one of biocompatible vesicles, liposomes, and micelles. 
     
     
         7 . The composition of  claim 1 , further comprising at least one active agent. 
     
     
         8 . The composition of  claim 7 , wherein the at least one active agent is selected from the group consisting of therapeutics, imaging agents, anti-inflammatory agents, antibiotics, proteins, platelet rich plasma, stem cells, degradation inducers of porous particles, and combinations thereof. 
     
     
         9 . The composition of  claim 4 , wherein the hydrogel porogen particles further comprise at least one biodegradable porous particle. 
     
     
         10 . The composition of  claim 9 , wherein the at least one biodegradable porous particle is a silicon porous particle. 
     
     
         11 . The composition of  claim 9 , wherein a surface of the at least one biodegradable porous particle is modified with a biodegradable polymer. 
     
     
         12 . The composition of  claim 11 , wherein the biodegradable polymer comprises agarose, a hydrogel, poly(lactic-co-glycolic acid) (PLGA), or a combination thereof. 
     
     
         13 . The composition of  claim 11 , wherein the at least one biodegradable porous particle facilitates or controls at least one of intracellular delivery of an active agent, bio-distribution of an active agent, stability of an active agent, and internalization of the porous particle by one or more cells or organelles. 
     
     
         14 . The composition of  claim 1 , wherein the at least one biodegradable reinforcing particle comprises a degradation inducer of one or more hydrogel porogen particles. 
     
     
         15 . The composition of  claim 14 , wherein the one or more hydrogel porogen particles comprise alginate. 
     
     
         16 . The composition of  claim 14 , wherein the degradation inducer comprises sodium citrate. 
     
     
         17 . The composition of  claim 1 , wherein at least one biodegradable reinforcing particle comprises a mesoporous silica particle. 
     
     
         18 . The composition of  claim 17 , wherein the mesoporous silica particle further comprises at least one active agent, at least one imaging agent, or a combination thereof. 
     
     
         19 . The composition of  claim 18 , wherein the at least one imaging agent comprises barium sulfate. 
     
     
         20 . The composition of  claim 1 , wherein at least one biodegradable reinforcing particle comprises elongated, rod-like microparticles, nanoparticles, or a combination thereof. 
     
     
         21 . The composition of  claim 1 , wherein the at least one biodegradable reinforcing particle is bound to the biodegradable matrix. 
     
     
         22 . The composition of  claim 21 , wherein the at least one biodegradable reinforcing particle is covalently bound to the biodegradable matrix through an acrylate moiety on a surface of the at least one biodegradable reinforcing particle. 
     
     
         23 . The composition of  claim 22 , wherein the biodegradable reinforcing particle further comprises at least one active agent. 
     
     
         24 . The composition of  claim 23 , wherein at least one active agent is selected from the group consisting of therapeutics, imaging agents, anti-inflammatory agents, antibiotics, proteins, platelet-rich plasma, cells, degradation inducers of porous particles, and combinations thereof. 
     
     
         25 . A composition comprising:
 (a) a biodegradable polymer matrix comprising poly(propylene fumarate);   (b) a population of biodegradable reinforcing particles, dispersed within the biodegradable polymer matrix, and comprised of porous oxide particles, porous semiconductor particles, or a combination thereof;   (c) a population of hydrogel porogen particles dispersed within the biodegradable matrix, and comprised of poly(lactic-co-glycolic acid) (PLGA); and   (d) at least one active agent.   
     
     
         26 . The composition of  claim 25 , wherein the at least one active agent is comprised within one or more of the biodegradable reinforcing particles, or within the population of hydrogel porogen particles. 
     
     
         27 . The composition of  claim 25 , wherein the population of hydrogel porogen particles comprises at least one of alginates, fibrins, and gelatins. 
     
     
         28 . The composition of  claim 25 , wherein the at least one active agent comprises an imaging agent, a therapeutic agent, or a combination thereof. 
     
     
         29 . The composition of  claim 25 , formulated as an injectable. 
     
     
         30 . A pharmaceutical formulation, suitable for human injection, that comprises:
 (a) a biodegradable polymer matrix comprising poly(propylene fumarate);   (b) at least one biodegradable reinforcing particle dispersed in the polymer matrix, wherein the at least one biodegradable reinforcing particle is selected from the group consisting of porous oxide particles and porous semiconductor particles; and   (c) a population of hydrogel porogen particles, dispersed within the biodegradable polymer matrix, that comprise poly(lactic-co-glycolic acid) (PLGA), and at least one therapeutic agent.