Optimizing natural human-derived decellularized tissue materials for periodontal bone defect repair

Periodontal disease is a major contributor to tooth loss worldwide in adults. Particularly, periodontal bone defect is a common clinical condition, yet current therapeutic strategies exhibit limited effectiveness. Recently, natural bone graft materials have attracted considerable interest for enhancing bone defect repair due to their superior biocompatibility and osteogenic capabilities. Nevertheless, clinically applicable human-derived biomaterials to boost bone regeneration are currently not accessible. Here, enlightened by the decellularization technique, we successfully prepared the human decellularized alveolar bone and tooth dentin tissues from healthy individuals and obtained micro-sized bioactive decellularized extracellular matrix (dECM) particles for treatment of periodontal bone defects. After characterizing the two representative dECM tissues and particles by multiple physiochemical approaches, we revealed that both human decellularized alveolar bone matrix particles (hDABMPs) and human decellularized tooth dentin matrix particles (hDTDMPs) possessed excellent biocompatibility. Furthermore, both biomaterials significantly enhanced the proliferation and osteogenic differentiation of human dental follicle stem cells, potentially contributing to periodontal bone formation. Indeed, in a rat model, both types of dECM microparticles were found to facilitate tissue regeneration at periodontal bone defect sites, demonstrating comparable efficacy for promoting bone defect repair. Collectively, this study provides an important basis for clinical exploration of natural human-derived micro-sized biomaterials for periodontal bone defect repair and opens a new path for periodontal disease treatment strategies.