Development of a novel hydroxylated recombinant human type III collagen TD-1-HrHC in Komagataella phaffii with transdermal and skin damage repair activity

Background Collagen has been proven to have significant potential applications value in the fields of on medical aesthetics and cosmetics. However, due to its large molecular weight, collagen is difficult to effectively penetrate the skin barrier and reach the designated location to exert the expected activities. Transdermal peptide TD-1 is a short peptide consisting of only 11 amino acids, which can assist proteins such as insulin and cytokines to penetrate the skin barrier and reach the dermis layer. To maximize the transdermal and the efficacy of Collagen III in skincare, the shortest functional fragment that containing a triple helix structure of collagen protein fused with TD-1 were designed and evaluated for its transdermal activity, safety and efficacy. Results The recombinant protein containing transdermal TD-1 fragment and a core active fragment of human collagen III (TD-1-HrHC) was co-expressed together with specific hydroxylase using the K. phaffii expression system, the products were purified by hydrophobic interaction chromatography (HIC) and ion-exchange chromatography (IEC). The TD-1-HrHC contains about 11.89% hydroxylation modifications that are similar to the natural human collagen III. The transdermal efficiency is 2077% measured by trans-well tests compare to the nature Collagen III isolated from animals. In addition, TD-1-HrHC able to promotes skin damage repairing through regulation series of barrier factors and differentiation factors in the HaCat cell model and promotes the repair of damaged skin and induces the generation of new-born collagen in mouse model. Moreover, it also shown an excellent ability to inhibit protein carbonylation on HaCat cells. Conclusion This study demonstrates that TD-1-HrHC can effectively cross the skin barrier and has profound ability to inhibit protein carbonylation of skin and promote skin damage repairing.