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 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 three-dimensional aerogel scaffold in this study has been synthesized through a versatile one-pot aqueous-based sol−gel hybridization/assembly of organosilane (tetraethyl orthosilicate) and silk fibroin (SF) biopolymer, followed by unidirectional freeze-casting of the as-prepared hybrid gel and supercritical drying. The developed ultralight 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 the hybrid aerogel lied in ∼0.5−18 μm and was systematically controlled with freeze-casting conditions. Together with high porosity (91−94%), high Young's modulus (∼4−7 MPa, >3 order of magnitude improvement compared to their pristine aerogel counterparts), and bone-type anisotropy in the mechanical compressive behavior, the silica-SF hybrid aerogel of this study acted as a very competent scaffold for bone tissue formation. The results of in vitro assessments revealed that the silica-SF aerogel is not only cytocompatible and nonhemolytic but also acted as an open porous microenvironment to trigger osteoblast cell attachment, growth, and proliferation on its surface within 14 days of incubation. Moreover, to support the in vitro results, in vivo bone formation within the aerogel implant in the bone defect site was studied. The X-ray radiology and microcomputed tomography analyses confirmed that a significant new bone tissue density formed in the defect site within 25 days of implantation. Also, in vivo toxicology studies showed a zero-toxic impact of the 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 a successful osseointegration process.

Mussel-inspired agarose hydrogel scaffolds for skin tissue engineering

“…By comparing these samples, it could be seen that AHG without PDA had the most compact structure. It is expected that the hydrogel with a more compact structure possesses more robust mechanical properties, which is in line with previous results [ 22 , [40] , [41] , [42] ]. The presence of PDA in APG3 was further confirmed by energy-dispersive X-ray (EDX) elemental mapping ( Fig.…”

Freeze Casting: From Low‐Dimensional Building Blocks to Aligned Porous Structures—A Review of Novel Materials, Methods, and Applications

“…The developed ultralight aerogels demonstrated a hierarchically organized porous structure with an interesting honeycomb micromorphology and microstructural alignment. [ 105 ]…”

“…While at the atomic‐scale numerous bioresorbable crystalline and amorphous material systems are under investigation for use in tissue engineering, the use of freeze‐casting methods opens up new avenues of progress in the design of biomaterial scaffolds that support cell growth in bone and nerve regeneration. [ 105,142 ] The biomimetic structures that can be formed through freeze‐casting can be tailored to mimic natural extracellular matrices (ECM) in terms of pore structure, chemical composition, and mechanical properties.…”

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…They used a unidirectional freeze-casting approach with ice as the structural directing agent, and adjusted reaction parameters during fabrication process to control the micromorphology of the resulting aerogel. 106 The microstructural pattern provided a platform for the attachment of osteoblast cells for growth, proliferation, osteogenic differentiation, mineralization, and eventual bone formation. The alignment of the materials comprised the morphological pattern of the scaffold, which was also closely related to pore formation.…”