Polymeric Hydrogels, Bioadhesive Biomaterials and Topical Therapeutics for Oral Mucosal Repair: A Systematic Review of Preclinical Efficacy, Effective Concentrations and Mechanisms of Action

Intraoral mucosal wounds face challenges around continuous salivary clearance, mechanical shear stress and polymicrobial exposure. Despite growing interest in topical interventions, a comprehensive synthesis of the biomaterial’s effective concentrations, bioadhesion strategies and molecular mechanisms remain limited. This systematic review aims to evaluate preclinical animal studies on polymeric hydrogels, bioadhesive biomaterials and topical therapeutics for oral mucosal repair. Following PRISMA 2020 guidelines (PROSPERO: CRD420261443129), three electronic databases were searched (PubMed, Scopus, and Web of Science) until June 2026. Thirty-five preclinical animal studies were evaluated across natural biopolymers, chemically modified/semi-synthetic biopolymers and synthetic hydrogel networks. The reported outcomes were vehicle and dose-dependent, with bioadhesive formulations demonstrating wet tissue adherence and prolonged residence time. The biomolecular findings reveal discrete model-specific associations rather than single unified mechanisms. Formulation of these biomaterials is linked to elevated pro-angiogenic markers (VEGF, CD31), extracellular matrix reorganisation (TGF-β1, Col1A1) and suppression of pro-inflammatory mediators (iNOS, IL-1β and TNF-α). SYRCLE assessment identified low risk selection/attrition bias, but performance/detection bias showed high risk due to unblinded applications. Although topical biomaterials facilitate oral mucosal repair in preclinical models, clinical translation remains constrained by animal model heterogeneity, non-standardised dosing metrics and methodological risk of bias.