The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field, such as collagen or hyaluronic acid, etc. However, the biosafety and efficacy of these implants are still challenged. In this study, a skin damage animal model was prepared by UV-photoaging and recombinant humanized type III collagen (rhCol III) was applied as a bioactive material to implant
in vivo
to study its biological effect, comparing with saline and uncrosslinked hyaluronic acid (HA). Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment. Histological observation, specific gene expression and other molecular biological methods were applied by the end of the animal experiment. The results indicated that rhCol III could alleviate the skin photoaging caused by UV radiation, including reduce the thickening of epidermis and dermis, increase the secretion of Collagen I (Col I) and Collagen III (Col III) and remodel of extracellular matrix (ECM). Although the cell-material interaction and mechanism need more investigation, the effect of rhCol III on damaged skin was discussed from influence on cells, reconstruction of ECM, and stimulus of small biological molecules based on current results. In conclusion, our findings provided rigorous biosafety information of rhCol III and approved its potential in skin repair and regeneration. Although enormous efforts still need to be made to achieve successful translation from bench to clinic, the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.