Calcium crosslinked macroporous bacterial cellulose scaffolds with enhanced in situ mineralization and osteoinductivity for cranial bone regeneration

The inherent biological inertness and lack of three-dimensional (3D) macroporous structures greatly hinder the use of pristine bacterial cellulose (BC) as a tissue engineering scaffold for bone regeneration. To address this issue, we developed a simple and effective strategy to fabricate a BC-based scaffold with excellent bioactivity and macroporous structure by crosslinking short-cut BC nanofibers using Ca2+. The Ca2+ crosslinked macroporous BC scaffold (MPBC@Ca) presents better structural stability due to the enhanced cellulose hydration. Importantly, the Ca2+ on the surface of BC nanofibers can serve as an active nucleation site to accelerate the deposition of hydroxyapatite (HAp), which is beneficial for the construction of biomimetic bone tissue extracellular matrix (ECM) microenvironment. The HAp-deposited MPBC@Ca scaffolds (HAp-MPBC@Ca) with biomimetic ECM microenvironment have excellent cytocompatibility and enhanced osteogenic differentiation of stem cells in vitro. Furthermore, the results of in vivo tests revealed that the HAp-MPBC@Ca scaffold has favorable osteoinductivity and accelerates cranial bone tissue regeneration. This study proposes a novel strategy to improve the bioactivity of BC and presents the great potential of biomimetic ECM microenvironment BC-based scaffold for repairing large cranial bone defects.