Mechanically Strong Silica-Silk Fibroin Bioaerogel: A Hybrid Scaffold with Ordered Honeycomb Micromorphology and Multiscale Porosity for Bone Regeneration

Abstract

Due to the synergic feature of individual components in hybrid (nano)biomaterials, their application in regenerative medicine has drawn a significant attention. Aiming to address all the current challenges of aerogel as a potent scaffold in bone tissue engineering application, we adopted a novel synthesis approach to synergistically improve the pore size regime and mechanical strength in the aerogel. The 3D aerogel scaffold in this study has been synthesized through a versatile one-pot aqueous based sol-gel hybridization/assembly of organosilane tetraethylorthosilicate, TEOS) and silk fibroin (SF) biopolymer followed by unidirectional freeze casting the as-prepared hybrid gel and supercritical drying. The developed ultra-light silica-SF aerogel hybrids demonstrated a hierarchically organized porous structure with interesting honeycomb shaped micromorphology and microstructural alignment (anisotropy) in varied length scales. The average macropore size of hybrid aerogel lied in 0.5-18 micrometer and was systematically controlled with freezecasting conditions. Together with high porosity (91-94%), high Youngs modulus (~ 4-7 MPa, > 3 order of magnitude improvement compared to their pristine aerogel counterparts), and bone-type anisotropy in the mechanical compressive behaviour, the silica-SF hybrid aerogel of this study acted as a very competent scaffold for bone tissue formation. Namely, the results of in vitro assessments revealed that silica-SF aerogel is not only cytocompatible and non-hemolytic but also acted as an open porous microenvironment to trigger the osteoblast cells attachment, growth and proliferation on its surface within 14 days of incubation. Moreover, in order to support the in vitro results, in vivo bone formation within the aerogels implant in the bone defect site has been studied. The X-ray radiology and micro-CT analyses confirmed a significant new bone tissue density formed in the defect site within 25days of implantation. Also, in vivo toxicology studies showed a zero-toxic impact of aerogel implant on the blood biochemical and hematological parameters. Finally, the study clearly shows the potential of aerogel as a bioactive and osteoconductive open porous cellular matrix for successful osseointegration process.