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

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.

Phosphoserine enhanced Cu-doped bioactive glass dynamic dual-network hydrogel for craniofacial bone defect repair

Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect reconstruction.However,in most hybrid hydrogels,poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties,clinical manipulation and repair efficacy.In this article,we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass(CuBG)and phosphoserine(PS),in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network.PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels.The CuBG/PS hydrogels exhibited suitable rheological properties(injectable,self-healing,shape-adaptable),bone tissue integrating ability and anti-bacterial property.Meanwhile,we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo,particularly when the ratio of CuBG to PS is lower than 3(9CB/3PS).This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.

Workflow and Principles for Precisely Designing a Custom-Made Polyetheretherketone Implant Applied in Irregular Craniofacial Bone Defects

Irregular craniofacial bone defects caused by craniofacial fractures always result in craniofacial bone and contour asymmetry and should therefore be reconstructed.Polyetheretherketone(PEEK)is an ideal substitute for autologous bone grafts and has been widely used in craniofacial bone defect reconstruction.The precise design of custom-made PEEK implants is particularly important to optimise reconstruction.Herein,the workflow and principles for the design and manufacture of PEEK implants are summarised,and a protocol for the precise design of an irregular craniofacial bone defect PEEK implant is presented.According to the method and principles,the design flow was efficient and could be standardised,and design errors could be avoided as much as possible.