A Bioactive Peptide-Functionalized Decellularized Tooth Matrix Composite with Dual Anti-inflammatory and Osteoinductive Effects for Enhanced Bone Regeneration
Bone defects present a significant clinical challenge, impairing facial integrity and essential functions, including mastication and speech. Moreover, current clinical approaches for mandibular defect repair have several limitations. Accordingly, this study aimed to develop and evaluate a novel composite scaffold by loading a bioactive peptide (PAP) onto a decellularized and demineralized tooth matrix (DDTM) to enhance bone regeneration under inflammatory conditions. Teeth scaffolds were prepared by sequential decellularization and demineralization. In vitro assays were used to evaluate cytocompatibility, osteoinductive activity, and anti-inflammatory effects using bone marrow stromal cells and lipopolysaccharide-stimulated RAW 264.7 macrophages. RNA sequencing and pathway enrichment analyses were performed to elucidate underlying mechanisms. In vivo bone regeneration was assessed in a rat calvarial critical-sized defect model using microcomputed tomography, histological staining, and immunohistochemistry. The PAP+Teeth composite significantly upregulated osteogenic markers and suppressed proinflammatory cytokines in vitro. Transcriptomic analyses revealed enrichment of osteogenesis-related pathways alongside downregulation of glycolysis and inflammatory signaling. In vivo, PAP+Teeth exhibited superior bone volume, density, and trabecular organization compared with controls. PAP-functionalized teeth scaffolds exhibit excellent biocompatibility, with dual anti-inflammatory and osteoinductive effects, resulting in significantly enhanced bone regeneration. This composite represents a promising strategy for mandibular defect repair in an inflammatory microenvironment.