Marine-Derived Injectable Hydroxybutyl Chitosan with Tunable Thermoresponsive Properties and Potential Anti-aging Applications.

Skin aging, largely driven by oxidative stress, leads to fibroblast senescence, deterioration of the extracellular matrix, and impaired regenerative capacity; however, effective biomaterial-based interventions remain limited. While marine-derived chitosan offers sustainable antioxidative potential, its poor solubility limits clinical use. In this study, we developed an injectable, thermoresponsive hydroxybutyl chitosan (HBC) hydrogel that combines intrinsic radical-scavenging activity with thermoresponsive modulation of the local hydrated microenvironment. HBC (degree of substitution: 1.88; Mw: 188 ± 34 kDa) demonstrated robust radical scavenging, reaching 80% for hydroxyl radicals at a concentration of 1.6 mg/mL. At 37 °C, HBC exhibited rapid, concentration-dependent gelation (40-60 s), forming hydrogels that exhibited time- and concentration-dependent increases in modulus and a characteristic 40% diameter shrinkage. HBC hydrogel extracts were not cytotoxic, maintaining metabolic activity levels near the positive controls for both L929 fibroblasts and human dermal fibroblasts (HDFs). In a hydrogen peroxide-induced senescence model using HDFs, the 5% HBC hydrogel led to a significant decrease in senescence-associated beta-galactosidase activity (>50%) and mitigated intracellular reactive oxygen species activity. Furthermore, HBC treatment effectively sustained collagen I synthesis. These findings support marine-derived HBC as a multifunctional, thermoresponsive biomaterial with potential for skin-regenerative and anti-aging applications involving oxidative stress modulation.