A Disulfide-Sticker Strategy for Marine Adhesive Coatings: From Deciphering Self-Assembly Mechanism to Functional Application in Hair Regeneration

Marine adhesive organisms commonly employ epidermal growth factor (EGF)-like domains for wet attachment, yet the molecular mechanisms guiding their self-assembly remain elusive. Here, we report a disulfide‑sticker strategy in the recombinant scallop adhesive protein Sbp9^Δ. Dynamic disulfide bonds, acting synergistically with Ca²⁺ coordination, orchestrate the multiscale hierarchical self-assembly of Sbp9^Δ by modulating its conformational heterogeneity. Spectroscopic and scattering analyses reveal that disulfide formation acts as a covalent sticker, rigidifying Sbp9^Δ into β-sheet-rich rod-like nanostructures, which direct orderly aggregation into extensive two-dimensional networks. The resulting coating exhibits robust wet adhesion across diverse substrates, accompanied by intrinsic antioxidant activity. As a proof of concept, the biocompatible Sbp9^Δ coating markedly promotes hair regeneration by enhancing angiogenesis, stimulating follicular cell proliferation, and effectively scavenging reactive oxygen species (ROS), exhibiting superior efficacy compared with minoxidil. In a mouse model of androgenetic alopecia, the Sbp9^Δ coating activates the follicular niche through the upregulation of Wnt signaling and the downregulation of calcium signaling, leading to robust hair follicle activation. By integrating insights from marine biology, biophysics, and materials science, this work elucidates a disulfide-mediated assembly paradigm in marine adhesives and translates it into a functional strategy for hair regeneration. © 2026 The Author(s). Advanced Science published by Wiley-VCH GmbH.