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 so...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.展开更多
基金National Research Foundation of Korea(2021R1A6A3A14039205)(Mirae Kim)National Institutes of Health/National Institute of Dental and Craniofacial Research(R01DE030480)(Russell R.Reid).
文摘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.
