Biofabrication of Gas-Foamed, Macroporous Nanofiber–Hydrogel Composites with Tunable Mechanics and mTCP Bioactivation for Advanced Bone Tissue Regeneration

Hydrogels, a type of water-filled 3D polymeric material, have been widely used in biomedicine for their enhanced cytocompatibility, easy availability, cost-effectiveness, and tunable mechanical properties. However, the requirement for stiff matrices for bone tissue engineering applications limits the use of soft hydrogel-like polymeric materials and requires extensive structural and biomechanical interventions. The dense polymeric network configuration also limits cellular infiltration into stiff hydrogel constructs. A composite of electrospun nanofibers with soft hydrogel matrices, called a nanofiber hydrogel composite (NHC), has recently gained tremendous attention for mitigating such challenges. However, the cellular infiltration of such systems remains a significant challenge that must be addressed to enhance their suitability for applications involving thicker constructs. Here, we report the fabrication of a gelatin-based macroporous nanofiber hydrogel composite (NHC) with osteoinductive microtricalcium phosphate (mTCP) fillers for potential applications in bone tissue engineering. Electrospun, silk-fibroin-based nanofiber mats were ultrasonically shredded and mixed with a gelatin-based hydrogel precursor solution containing mTCP fillers. The in situ fabricated gel block was made porous using a modified gas foaming technique and was further investigated using the MG63 osteoblastic cell line of human origin to study its potential application in bone tissue engineering. The porous NHC fabrication reported in this article has the potential to be used for scaffolds with tunable mechanical properties according to the user's needs and, therefore, can be applied in a wide range of future biomedical and tissue engineering applications.