Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration

Approaches to regenerating bone often rely on the integration of biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches face challenges due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60% hydroxyapatite content resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite, customizable in situ to fit the defect. This hybrid phasic porous CSS mimics the bone microenvironment (inorganic and organic) while allowing independent control of each material phase (rigid and soft). The CSS stimulates osteogenic differentiation in vitro and in vivo. Moreover, it promotes M2 polarization and blood vessel ingrowth, which are crucial for supporting bone formation. Our comprehensive micro-CT analysis revealed that within 4 weeks in a critical-size defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.