A chitosan-based thermosensitive hydrogel incorporating propranolol nanoparticles to promote early osseointegration and peri-implant soft-tissue healing

Abstract

Based on clinical evidence that propranolol enhances bone mineral density, improves early implant stability, and promotes soft-tissue healing, this study investigated whether its local application around dental implants could coordinately promote early osseointegration and gingival tissue repair. To enable localized drug delivery while minimizing systemic adverse effects such as hypotension associated with oral administration, a chitosan-based thermosensitive hydrogel incorporating propranolol-loaded nanospheres was developed and systematically characterized. Cell models related to osseointegration and gingival healing, including MC3T3-E1, Hacats, and HGFs, were used for in vitro evaluation, and an SD rat jaw implant model was established in vivo. Multiple assays, including CCK-8, live/dead staining, scratch assays, immunofluorescence, Alizarin Red staining, histological staining, immunohistochemistry, and micro-CT, were performed to assess cell proliferation, migration, adhesion, osteogenic differentiation, soft-tissue-related protein expression, and early peri-implant healing. The results demonstrated that the hydrogel exhibited favorable drug-loading capacity and sustained release behavior. It significantly enhanced cellular proliferation, migration, and adhesion and upregulated osteogenic markers (BGLAP, BMP2, RUNX2) and gingival healing-related proteins (LAMA3, ITGB4), thereby accelerating early peri-implant bone formation and gingival repair. This study is the first to apply propranolol to the integrated regeneration of peri-implant hard and soft tissues, establishing a dual sustained-release thermosensitive hydrogel system for localized delivery. The findings provide a novel and effective strategy for improving postoperative peri-implant healing.