Development of a Collagen-Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation.

Background

Effective regenerative therapeutics for acute and chronic wounds remain a critical unmet need in biomedicine.

Objectives

This study aimed to develop novel collagen-cerium oxide nanoparticle hydrogels designed to enhance cellular metabolism, proliferation, and antioxidant/antimutagenic activity, accelerating wound regeneration in vivo.

Methods

Collagen-nanocerium composites were synthesized by combining a collagen extract with cerium oxide nanoparticles at defined concentrations. In vitro assays using human fibroblasts identified two formulations that enhanced proliferation and metabolic activity by 42-50%. FTIR spectroscopy confirmed chemical interactions within the composite matrix. Toxicity, antioxidant, and antigenotoxic effects were evaluated using Escherichia coli MG1655 lux-biosensors to assess their general toxicity, antioxidant and pro-oxidant activities, and antigenotoxic and promutagenic effects. In vivo efficacy was tested in Wistar rats with full-thickness skin wounds. Treated groups were compared to untreated controls and Dexpanthenol-treated positive controls. On days 3, 7, and 14, healing was assessed clinically, histologically, and morphometrically.

Results

Biosensor analysis demonstrated non-toxicity and antigenotoxic activity of the nanocomposites, reduced DNA damage by up to 45%, providing 31-49% protection against H2O2 and 15-23% against O2- radicals. The animal study results demonstrated significantly accelerated healing with both nanocomposites versus control and comparison groups, evidenced by improved tissue regeneration, reduced inflammation, and increased fibroblast infiltration.

Conclusions

The developed hydrogels exhibit promising pharmacological profiles, including antioxidant, antimutagenic, anti-inflammatory, and pro-regenerative effects validated across in vitro and in vivo models.