Bioorthogonal "Click Chemistry" Bone Cement with Bioinspired Natural Mimicking Microstructures for Bone Repair

Current bone cement systems often demand free radical or metal-related initiators and/or catalysts for the crosslinking process, which may cause serious toxicity to the human body. In addition, the resultant dense scaffolds may have a prolonged degradation time and are difficult for cells to infiltrate and form new tissue. In this study, we developed a porous "click" organic-inorganic nanohybrid (PO-click-ON) cement that crosslinks via metal-free biorthogonal click chemistry and forms porous structures mimicking the native bone tissue via particulate leaching. Strain-promoted click reaction enables fast and efficient crosslinking of polymer chains with the exclusion of any toxic initiator or catalyst. The resulting PO-click-ON implants supported exceptional in vitro stem cell adhesion and osteogenic differentiation with a large portion of stem cells infiltrated deep into the scaffolds. In vivo study using a rat cranial defect model demonstrated that the PO-click-ON system achieved outstanding cell adsorption, neovascularization, and bone formation. The porous click cement developed in this study serves as a promising platform with multifunctionality for bone and other tissue engineering applications.