Dual-functional probiotic hydrogel with puerarin integration for microbiota-neuroimmune regulation in antibiotic-free periodontitis therapy

Periodontitis is an inflammatory disease caused by the imbalance of the periodontal microbial ecosystem. Traditional treatment methods not only kill pathogenic bacteria but also inhibit the growth of beneficial bacteria, thereby disrupting the balance of the oral microbial ecosystem. In this study, chitosan, hyaluronic acid, and puerarin were coated on live Lactobacillus rhamnosus to form probiotic-based PSCLR nanoparticles. Subsequently, these nanoparticles were encapsulated in hydrogel microspheres through emulsion polymerization and immobilized in the hydrogel network via the covalent cross-linking of methacrylate-modified hyaluronic acid. This hydrogel restores the balance of oral microbiota by reducing pathogenic bacteria and promoting probiotic diversity, which helps maintain ecological stability and minimize risks associated with microbial community dysbiosis. In addition, puerarin in the gel achieves analgesic and neuromodulatory effects by specifically antagonizing the P2X₃ receptor, which affects pain transmission. This study provides a potential strategy for the antibiotic-free treatment of periodontitis and the neuropathic pain associated with it.