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 (∼75% by weight) and with varying mechanical properties (38 ± 1.0 to 181 ± 5.9 kPa). These macroporous scaffolds have ∼80% porosity with an average pore size of 60 μm. 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 (∼35% release) and FITC-BSA (∼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 ∼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.
Keywords: biocompatible; biodegradable; cross-linking; drug delivery; hybrid scaffolds; ice-templating; mechanical; mesoporous silica materials; release; silk.