Silk-Mesoporous Silica-Based Hybrid Macroporous Scaffolds using Ice-Templating Method: Mechanical, Release, and Biological Studies

Development of biocompatible, biodegradable, and drug-eluting macroporous three-dimensional scaffolds that mimic the extracellular matrix of cells remains an important challenge in tissue engineering. In this endeavor, we report the preparation of self-standing macroporous scaffold composed of the natural biopolymer silk fibroin and mesoporous silica particle using the ice-templating strategy. Using methanol as a physical cross-linker, we were able to make self-standing scaffolds with very high mesoporous silica content (similar to 75% by weight) and with varying mechanical properties (38 +/- 1.0 to 181 +/- 5.9 kPa). These macroporous scaffolds have similar to 80% porosity with an average pore size of 60 mu m. Scaffolds that encapsulated the small molecule doxorubicin (as a model drug) and macromolecule fluorescein isothiocyanate conjugate-bovine serum albumin (FITC-BSA) (as a model protein) were also prepared. We demonstrate that the release behavior of encapsulated molecules like doxorubicin (similar to 35% release) and FITC-BSA (similar to 47% release) is largely influenced by their interaction with the mesoporous silica particles and the silk fibroin. The biodegradability property of silk hybrid scaffolds is also determined in the presence of protease enzyme, which demonstrates similar to 90% degradation in 21 d. Biological studies on ice-templated hybrid silk scaffolds demonstrate excellent biocompatibility, which indicates that hybrid scaffolds are promising candidate for therapeutically relevant repair and regeneration of soft tissues such as tendon and nascent bone.