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

Le résumé fourni par la source

Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging 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 micro-continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60 wt% hydroxyapatite resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect, which is expected to enhance surface contact with surrounding tissue and facilitate biointegration. The antioxidative properties of citrate polymers prevent long-term inflammatory responses. The CSS stimulates osteogenesis in vitro and in vivo. Within 4 weeks in a calvarial critical-sized bone defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Through spatial transcriptomics, we demonstrated the comprehensive biological processes of CSS for prompt osseointegration. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

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