•The eLHBC wound dressing was inspired by the adhesion mechanism of mussels.•The ε-Poly-l-lysine endowed eLHBC with highly efficient antimicrobial activity.•The BMSCs were encapsulated in eLHBC to promoting cell proliferation.•The biomimetic tissue-affinity hydrogel could promote complete skin regeneration. Hydrogels have gained great attentions as wound dressing. Binding to the tissue and preventing wound infection were the basic requirements for an “ideal dressing”. We employed l-DOPA and ε-Poly-l-lysine to modify thermo-sensitive hydroxybutyl chitosan (HBC) to obtain (l-DOPA) - (ε-Poly-l-lysine)-HBC hydrogels (eLHBC). The eLHBC exhibited an almost 1.5 fold (P < 0.01) increase in wet adhesion strength compared to HBC. Upon the introduction of ε-Poly-l-lysine, eLHBC presented inherent antimicrobial property and prevented wound infection and inflammation response. Bone marrow mesenchymal stem cells (BMSCs) encapsulated in the eLHBC (BMSCs ⊂ eLHBC) could secret cytokins and growth factors via paracrine and promote the migration of fibroblast cells. BMSCs ⊂ eLHBC enhanced the complete skin-thickness wound healing via promoting collagen deposition and inhibiting infection and inflammation in vivo with wound closure rate being above 99 % after 15 days. The bioinspired, tissue-adhesive eLHBC could serve as advanced wound dressings for facilitating tissue repair and regeneration.