Biointerface-engineered trabecular scaffolds integrating chitosan/icariin self-assembly and mild photothermal...

The regeneration of critical-sized bone defects remains a major clinical challenge due to the lack of scaffold systems capable of coordinating physical and biochemical cues at the biointerface to effectively regulate osteogenesis. Herein, we report a biointerface-engineered, trabecular-like scaffold fabricated by fused deposition modeling, integrating polydopamine-modified hydroxyapatite (pHAP)-reinforced poly(L-lactic acid) with a chitosan/icariin (CA) self-assembled microstructure to synergistically regulate osteogenesis. The pHAP modification markedly enhanced interfacial adhesion, hydrophilicity, mechanical resilience, and near-infrared (NIR) photothermal responsiveness of the scaffold, while the CA self-assembly generated hierarchical microfilaments enabling sustained icariin release and improved cell-material interactions. In vitro studies demonstrated that the multifunctional scaffold significantly promoted bone mesenchymal stem cell adhesion, spreading, and osteogenic differentiation, particularly under mild photothermal stimulation, as evidenced by elevated alkaline phosphatase activity, extracellular matrix deposition, calcium mineralization, and osteogenic gene expression. In vivo implantation in a rat calvarial defect model revealed that the CA-functionalized scaffold markedly accelerated new bone formation, collagen deposition, and neovascularization without eliciting adverse inflammatory responses. Transcriptomic analysis further revealed the activation of osteogenesis- and biointerface-related signaling pathways, including PI3K-Akt signaling and extracellular matrix-receptor interactions, providing mechanistic insight into the scaffold-mediated regenerative effects. Collectively, this study demonstrates that the rational integration of interfacial chemistry, hierarchical microtopology, and photothermal regulation within a single trabecular scaffold offers an effective strategy for synergistically enhancing osteogenesis and angiogenesis, highlighting its potential for bone tissue engineering applications.