TD-1-HrHC, a novel hydroxylated recombinant type III collagen, boosts transdermal efficiency 2077% and repairs skin damage

Effective delivery of therapeutic agents across the skin barrier remains a significant challenge, particularly for large molecules like collagen. While Type III collagen (COL3A) is crucial for tissue repair and skin health, its high molecular weight severely limits topical penetration and therapeutic efficacy. Current collagen-based products often struggle to reach the dermis, where they can exert their full regenerative potential. This study addresses this gap by engineering a fusion protein, combining a potent transdermal peptide (TD-1) with a functional fragment of human collagen III, aiming to enhance both penetration and biological activity.

Researchers engineered a recombinant protein, TD-1-HrHC, by fusing the transdermal peptide TD-1 with a core active fragment of human collagen III. This construct was co-expressed with a specific hydroxylase in the Komagataella phaffii system to ensure proper post-translational modification. Products were purified using hydrophobic interaction chromatography (HIC) and ion-exchange chromatography (IEC). Transdermal efficiency was quantified via trans-well tests, comparing TD-1-HrHC to natural animal-derived collagen III. Efficacy was assessed in HaCat cell models for barrier factor regulation and protein carbonylation, and in a mouse model for damaged skin repair and new collagen induction.

The engineered TD-1-HrHC protein exhibited approximately 11.89% hydroxylation modifications, closely mimicking natural human collagen III. Critically, trans-well tests demonstrated a remarkable 2077% increase in transdermal efficiency for TD-1-HrHC compared to natural animal-derived collagen III. This significant enhancement suggests superior skin penetration. In HaCat cell models, TD-1-HrHC effectively promoted skin damage repair by regulating a series of barrier factors and differentiation factors. Furthermore, it displayed an excellent ability to inhibit protein carbonylation on HaCat cells, a marker of oxidative stress and aging. > In a mouse model, TD-1-HrHC actively promoted the repair of damaged skin and induced the generation of new-born collagen, confirming its regenerative potential in vivo.