Periodontitis is a common inflammatory periodontal disease characterized by the destruction of bone tissue and requires an integrated treatment approach. In this study, an intelligent scaffold based on a collagen-hyaluronic matrix was developed that provides pH-dependent metronidazole release and prolonged delivery of recombinant bone morphogenetic protein-2 (rhBMP-2). Scaffold demonstrated pronounced antimicrobial activity against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, inhibiting the formation of bacterial biofilms by 75±6% compared with the control. The kinetics of metronidazole release showed significant pH sensitivity: at pH 5.5, 78±5% of the drug was released in 72 hours, whereas at physiological pH 7.4, only 25±3% was released. In vitro studies have confirmed excellent cytocompatibility of the scaffold with osteoblast-like MC3T3-E1 cells and a significant increase in the expression of osteogenic markers (Runx2, OCN, COL1A1). In vivo experiments on a rat periodontitis model revealed that the use of a scaffold leads to the restoration of 78±6% of bone volume after 8 weeks, which significantly exceeds the results of standard treatment (45±5%). Histological analysis confirmed the formation of mature bone tissue with pronounced vascularization in the experimental group. The developed scaffold is a promising combined system for the treatment of periodontitis, combining targeted antimicrobial therapy and active stimulation of tissue regeneration. The results obtained open up new possibilities for the clinical application of intelligent biomaterials in regenerative periodontology.
