Figure 3.

Snail mucus-derived innovations in wound healing and drug delivery. (a) Dried snail-mucus glue (d-SMG) mechanism in wound healing. Snail adhesive: The snail-mucus hydrogel has a double-network structure. Proteins form a 3D skeleton that binds with linear snail glycosaminoglycan (s-GAG), resulting in supramolecular entanglement. This is further reinforced by electrostatic interactions between positive amino or guanidine groups and negatively charged sulfate and carboxyl groups in s-GAG. Other bonds, such as hydrogen, π–π, and hydrophobic interactions, are prevalent due to the high presence of hydroxyl, aromatic, and aliphatic amino acids. Divalent cations (Ca²⁺ and Mg²⁺) in the mucus modify gel elasticity via complexation and electrostatic interactions, resulting in a naturally resilient and cohesive snail adhesive. Tissue adhesion: On moist tissue surfaces, water blocks hydrogen bond receptors and donors, restricting interactions. The hydrophilic nature of sulfated GAG in d-SMG, attributed to its rich sulfates, carboxyl, and hydroxyl groups, effectively absorbs water. This removal of interface water facilitates supramolecular interactions, promoting tissue adhesion. Adapted with permission from ref (6). Copyright 2023 Springer Nature. (b) AFG/GelMA hydrogel for wound healing. This bioinspired hydrogel is formed by covalently linking the polyanionic snail glycosaminoglycan (AFG) with positively charged methacrylated gelatin (GelMA) polymers. Upon exposure to light, it undergoes in situ gelation directly at the wound site, establishing an array of covalent and noncovalent bonds that ensure rapid solidification. Mechanistically, the AFG within the hydrogel binds to inflammatory cytokines, inhibiting the TLR4/NF-κB signaling pathway. This results in an improved wound microenvironment by lowering inflammatory cytokine levels and fostering macrophage M2 polarization, which further supports epithelialization, angiogenesis, and collagen deposition. Adapted with permission from ref (41). Copyright 2023 Elsevier. (c) Gelatin and snail slime-based patches. Gelatin-based films demonstrate increased flexibility, stretchability, and adhesion with higher slime content and are proposed for cutaneous drug delivery. With Fluconazole as a model drug, snail slime also prevented drug recrystallization, enhancing skin permeation and film flexibility. Adapted with permission from ref (69). Copyright 2021 Elsevier.