Activation of bone tumor-eating macrophages via assembling and co-delivering 3D printed scaffold.

Abstract

The current post-surgery treatment of bone tumors with 3D-printed implants is facing the dilemma of difficulty in reducing the recurrence rate, which is closely related to the inability of the implants to reverse M2 polarization and the loss of tumor phagocytosis of macrophages caused by residual tumor cells. In this study, a multifunctional therapeutic implant activating local tumor-eating macrophages and promote bone regeneration in stages was developed by assembling a co-delivery system that enriched CSF-1R inhibitors within the internal porous structure and immobilizes anti-SIRPɑ on the surface based on boron-nitrogen coordination bonds onto an aldehyde-rich 3D printed calcium phosphate scaffold using dynamic covalent bonds. The phenylboric acid-modified mesoporous silica nanoparticle served as an efficient drug carrier for the enrichment of CSF-1R inhibitor and stable binding of antibodies while preserving their bioactivity. The co-delivery system was assembled onto the calcium phosphate scaffold through loading via the HBC network, enabling sustained release in the targeted treatment area. This efficiently blocked the MCSF/CSF-1R and CD47/SIPRɑ signaling interactions between tumor cells and macrophages, thereby inhibiting M2 polarization of macrophages while preserving their phagocytic activity and inhibiting tumor recurrence. Afterward, gradual disintegration of the assembled structure exposed the calcium phosphate and silicon-based core, which promoted bone tissue repair. In summary, the stably assembled therapeutic scaffold with a co-delivery system targeting the regulation of tumor-eating macrophages in situ provides a new strategy for the suppression of tumor immune escape and recurrence following surgery.