Abstract
About this talk
Introduction: Large mandibular bone defects are characterized by ischemia, hypoxia, insufficient vascularization, and impaired bone remodeling. A bone-matrix-inspired functionalized hydrogel scaffold was developed to promote angiogenesis and restore bone remodeling under hypoxic conditions.
Materials and methods: Piezoelectric ZnO nanoparticles with a hydrothermal carbon coating were synthesized via a hydrothermal process and further functionalized with L-arginine through Zn²⁺ coordination and coating-mediated adhesion. The resulting nanoparticles were incorporated into a bioink to fabricate 3D-printed porous hydrogel scaffolds. Scaffold physicochemical properties, biodegradability, and ion-release behavior were characterized, while molecular dynamics simulations were used to investigate functionalized interfacial interactions. Under normoxic (21% O₂) and hypoxic (1% O₂) conditions, osteogenic, osteoclastic, and angiogenic responses were evaluated in vitro. Transcriptomics, network pharmacology, molecular docking, and cellular assays were integrated to investigate the underlying osteogenesis–angiogenesis coupling mechanisms. In vivo regenerative efficacy was assessed in a murine mandibular defect model at 4 and 8 weeks. Data are presented as mean ± standard deviation (n ≥ 3) and analyzed by one-way ANOVA followed by Tukey's test (P < 0.05).
Results: The scaffold exhibited a well-defined porous architecture, good biocompatibility, and favorable biodegradability. It promoted balanced bone remodeling by activating TRPM7-mediated Ca²⁺ signaling, increasing ALP, COL1A1, RUNX2, and OCN expression while suppressing osteoclast-related genes, including Rank, Rankl, and Mcsf. Under hypoxia, the scaffold preserved mitochondrial function in BMSCs and enhanced paracrine signaling, thereby improving cellular adaptation to the hypoxic microenvironment. In HUVECs, it modulated NO signaling and increased VEGF, CD31, and NOS3 expression, promoting angiogenesis. In vivo, the scaffold enhanced osteogenesis–angiogenesis coupling, promoted new bone formation and maturation, reduced osteoclastic activity, and substantially improved mandibular bone regeneration.
Conclusion: This bone-matrix-inspired 3D-printed hydrogel scaffold coordinated osteogenesis, bone remodeling, and angiogenesis in an ischemic and hypoxic microenvironment. Integrating biomimetic design with hypoxia-adaptive regulation offers a promising strategy for ischemic and hypoxic bone regeneration.
Keywords: Bone-matrix-inspired structure; functionalized 3D printing; osteogenesis–angiogenesis coupling; hypoxia adaptation; bone regeneration
Speaker
About the speaker
