Calcium Butyrate-Integrated Bioadhesive Hydrogel: a Promising Therapeutic Platform for Inflammation Control and Wound Regeneration

Abstract

Purpose Butyric acid (a short-chain fatty acid) has anti-inflammatory and wound-healing potential but its direct use is limited by instability, odor, and irritancy. This study asked whether loading calcium butyrate (CAB) into a bioadhesive hydrogel suited for dermal delivery would yield acceptable physicochemical performance, sustained release, cytocompatibility, antiinflammatory activity, pro-migratory/wound-closure effects, and non-irritancy. Methods Hydrogels were prepared with carboxymethyl cellulose, xanthan gum, glycerin, and rose water, generating a blank matrix (F1) and a CAB-loaded system (F1-CAB). Formulations were characterized for pH, viscosity, CAB conten in the formulationt, texture/spreadability, rheology/thermal behavior, and in-vitro release kinetics. Biological evaluations followed ISO 10,993 principles using L929 fibroblasts, RAW 264.7 macrophages, and reconstructed human epidermis models. Endpoints included cell viability (cytotoxicity), nitrite inhibition (anti-inflammatory activity) versus CAB alone, fibroblast migration/wound-closure assays, and in-vitro irritation (tissue viability). Results CAB incorporation increased viscosity, bioadhesion, and viscoelastic strength. F1-CAB exhibited shear-thinning behavior and superior thermal stability, consistent with Cat+-mediated crosslinking. CAB release was sustained. The formulation showed excellent cytocompatibility with viability > 70% at all concentrations tested. At 1 mg/mL, F1-CAB produced 34% greater nitrite inhibition than CAB alone. F1-CAB enhanced fibroblast migration in a dose-dependent manner, accelerating wound closure. Reconstructed epidermis viability remained > 80%, indicating non-irritant properties. Conclusion A CAB-loaded bioadhesive hydrogel achieved favorable physicochemical/mechanical profiles, sustained release, robust anti-inflammatory effects, and pro-healing activity while maintaining biocompatibility and non-irritancy. These findings support CAB hydrogels as a promising dermal platform for inflammatory skin conditions and regenerative applications, meriting further preclinical development.