A Disulfide-Sticker Strategy for Marine Adhesive Coatings: From Deciphering Self-Assembly Mechanism to Functional...

Area of Science:

• Biomaterials Science
• Marine Biology
• Regenerative Medicine

Background:

• Marine organisms utilize epidermal growth factor (EGF)-like domains for wet adhesion, but their self-assembly mechanisms are not fully understood.
• Understanding these mechanisms can lead to novel biomaterials for applications like tissue regeneration.

Purpose of the Study:

• To elucidate the molecular mechanisms of self-assembly in marine adhesive proteins.
• To develop a novel biomaterial for hair regeneration based on marine adhesive strategies.

Main Methods:

• Recombinant scallop adhesive protein Sbp9Δ was engineered with a disulfide-sticker strategy.
• Dynamic disulfide bonds and Ca2+ coordination were investigated for their role in protein self-assembly using spectroscopic and scattering analyses.
• The Sbp9Δ coating's wet adhesion, antioxidant activity, and efficacy in promoting hair regeneration in a mouse model of androgenetic alopecia were evaluated.

Main Results:

• Disulfide formation in Sbp9Δ acts as a covalent sticker, promoting β-sheet-rich nanostructure formation and hierarchical self-assembly into 2D networks.
• The Sbp9Δ coating demonstrated robust wet adhesion and intrinsic antioxidant activity.
• Sbp9Δ coating significantly promoted hair regeneration by enhancing angiogenesis, stimulating follicular cell proliferation, scavenging reactive oxygen species (ROS), and activating the follicular niche via Wnt signaling.

Conclusions:

• A disulfide-mediated hierarchical self-assembly paradigm was elucidated for marine adhesives.
• The engineered Sbp9Δ protein provides a biocompatible coating with robust wet adhesion and antioxidant properties.
• This marine-inspired strategy offers a promising new therapeutic approach for hair regeneration, outperforming minoxidil in preclinical models.