Modulating Oxidative Stress and Inflammatory Responses of Aloe vera–Silk Fibroin–Chitosan Gel Formulation in Macrophages and Diabetic Fibroblasts Under Chronic Inflammatory-like Conditions

Chronic and diabetic wounds are characterized by persistent inflammation, excessive oxidative stress, and impaired cellular responses, collectively leading to delayed tissue repair. This study aimed to evaluate a thermoresponsive gel incorporating Aloe vera (AV) extracts and silk fibroin (SF), focusing on its biocompatibility, anti-inflammatory, antioxidant, and pro-regenerative potential. The AV: SF mixture and gel formulation were evaluated in macrophage-like THP-1 cells, and human diabetic dermal fibroblasts (HDdF) under non-induced and LPS/IL-6/TNF-α-induced inflammatory conditions. Both formulations maintained high cell viability across all cell types, indicating good biocompatibility. Under inflammatory conditions, both the AV: SF mixture and gel significantly reduced intracellular ROS levels and suppressed TNF-α and IL-1β secretion. In addition, NF-κB p65 activation was attenuated in both macrophage-like THP-1 cells and HDdF. Macrophage-like THP-1 cells displayed the M2 (CD80low/CD206high) phenotype, indicating modulation of macrophage polarization toward wound remodeling and repair. Overall, the AV: SF-based gel system demonstrated coordinated antioxidant, anti-inflammatory, and pro-regenerative effects in vitro. These findings support its potential as a multifunctional biomaterial for modulating inflammation-associated cellular dysfunction in chronic and diabetic wound environments.