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A Rationally Engineered COL17A1-Mimetic Recombinant Peptide Regulating Basement Membrane Biointerfaces and Epidermal Redox Homeostasis
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DOI：10.1016/j.eng.2026.07.019.png)
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Abstract
En 中文
Type XVII collagen (COL17A1) deterioration compromises basement membrane (BM) integrity, disrupts dermal–epidermal adhesion, and contributes to skin barrier dysfunction under ultraviolet (UV) and oxidative stress. However, restoring COL17A1-associated extracellular functions remains a key challenge in skin-directed biomaterial design. Here, we report RCP17, a sequence-optimized COL17A1-mimetic recombinant peptide engineered by rationally integrating five functional ectodomain segments into a compact multidomain construct. This domain-integration strategy minimizes redundant collagen repeats while enabling the coordinated reinforcement of BM biointerfaces and the regulation of redox homeostasis. Molecular and biophysical characterization verified the identity, purity, and collagen-like structural features of RCP17. Molecular docking predicted structurally plausible interactions with epidermal growth factor receptor (EGFR) and integrin β4 (ITGB4), and surface plasmon resonance analysis further confirmed a measurable micromolar-affinity interaction between RCP17 and the EGFR ectodomain. In keratinocytes and ex vivo human skin explants, RCP17 upregulated COL17A1 expression and preserved BM architecture; furthermore, it was associated with EGFR–tissue inhibitor of metalloproteinases 1 (TIMP1)–matrix metalloproteinase (MMP)-related proteolytic regulation. In parallel, RCP17 attenuated oxidative stress, as supported by H2O2/N-acetylcysteine (NAC) rescue assays, nuclear factor erythroid 2-related factor 2 (NRF2)-associated antioxidant responses, and Ca2+–calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)–AMP-activated protein kinase (AMPK)-related signaling changes. Transmission electron microscopy further revealed that RCP17 partially preserved hemidesmosome-associated ultrastructure and maintained lamina lucida–lamina densa continuity under UV stress. In a double-blind, placebo-controlled human efficacy study (n = 71; Institutional Review Board (IRB) No. E20240228A), topical RCP17 was well-tolerated and associated with favorable changes in noninvasive skin biophysical and imaging parameters, including hydration, erythema, wrinkle-related parameters, dermal density, gloss, and elasticity-related indices. Collectively, these findings establish RCP17 as a translationally relevant COL17A1-mimetic recombinant biomaterial that supports BM structural preservation and redox regulation in human skin models, demonstrating a functional domain-integration strategy for engineering multifunctional, collagen-inspired peptides for skin biointerface modulation and photodamage-associated skin protection.
Keywords:
Type XVII collagen
Recombinant biomaterial
Basement membrane
Skin biointerface
EGFR–TIMP1–MMP
CAMKK2–AMPK–NRF2
Oxidative stress
Human efficacy study
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