Multifunctional dual drug-loaded Gel-Alg/MINO/MEL composite hydrogel for combating three-dimensional multi-species biofilm and experimental periodontitis treatment.

OBJECTIVES: Adjunctive drug therapy is indispensable in periodontitis treatment. Currently, such pharmacotherapy is not ideal, so new formulations need to be explored to optimize prolonged in situ slow release of active ingredients, biocompatibility, and preparation costs. This study constructed an injectable dual drug delivery composite hydrogel system (Gel-Alg/MINO/MEL) to locally deliver minocycline hydrochloride (MINO) and melatonin (MEL) for antibacterial, anti-inflammatory, antioxidant effects and bone formation. MATERIALS AND METHODS: We tested the release kinetics of Gel-Alg/MINO/MEL, evaluated its in vitro and in vivo biocompatibility, and detected its in vitro effects on multi-species biofilm, pro-inflammatory cytokines, related genes/proteins and reactive oxygen species, as well as in vivo effects on periodontal inflammation and tissue reconstruction. RESULTS: Release kinetics showed Gel-Alg/MINO/MEL continuously released MINO and MEL for over 10 days with good biocompatibility. In vitro, it inhibited biofilm formation, reduced pro-inflammatory cytokines, increased related genes/proteins expression and scavenged excessive reactive oxygen species; in vivo, it relieved periodontal inflammation and promoted tissue reconstruction and collagen fiber attachment. CONCLUSIONS: The Gel-Alg/MINO/MEL hydrogel has promising potential as a local drug delivery system for treating periodontitis, with favorable sustained release and biocompatibility. CLINICAL RELEVANCE: Regular placement of the Gel-Alg/MINO/MEL composite hydrogel in periodontal pockets, in conjunction with basic clinical periodontal treatment, might remodel the bone and soft tissues lost during periodontitis. Therefore, this is expected to be a more effective medication-assisted treatment modality for refractory periodontitis.