A radix dipsaci-loaded gelatin methacryloyl nanocomposite hydrogel with slow release and osteogenic effects.

Abstract

Periodontitis induce alveolar bone destruction, which may result in tooth loosening, exfoliation, or oral functional impairment in severe cases. The development of novel therapeutic agents with sustained efficacy and robust mechanical properties represents a critical unmet need for clinical management of bone defect-related diseases. We investigated the efficacy of Radix Dipsaci (RD), a traditional Chinese medicinal herb, and its derivatives in bone defect therapy by incorporating RD into a nanocomposite hydrogel composed of gelatin methacryloyl (GelMA) and silicate nanoplatelets (SN), yielding an RD-loaded nanocomposite hydrogel (GelMA-SN-RD). The engineered hydrogel exhibited prolonged degradation kinetics, enhanced mechanical properties, and sustained, gradual release of RD bioactive components. GelMA-SN-RD hydrogel significantly upregulated the expression of osteogenesis-related genes and proteins in both physiological and inflammatory microenvironments. In vitro studies using MC3T3-E1 osteoblasts revealed that GelMA-SN-RD hydrogel possessed excellent biocompatibility, significantly increased alkaline phosphatase activity, upregulated osteogenic gene/protein expression, and promoted extracellular matrix mineralization. Moreover, we were delighted to discover that RD endowed the GelMA-SN-RD hydrogel with outstanding activity against Porphyromonas gingivalis. In vivo evaluation in a rat periodontitis model via micro-computed tomography (micro-CT) and immunohistochemical analysis further validated the hydrogel's superior bone regenerative capacity and anti-inflammatory effects, as evidenced by enhanced new bone formation and reduced inflammatory cell infiltration. Collectively, these findings highlight the promising potential of GelMA-SN-RD nanocomposite hydrogel as a dual-function biomaterial for bone tissue engineering applications, integrating mechanical support, controlled drug release, osteogenic induction, antibacterial and anti-inflammatory activity.