ABSTRACT: The combination of multiple physiological (swelling, porosity, mechanical, and biodegradation) and biological (cell/tissue-adhesive, cell proliferation, and hemostatic) properties on a single hydrogel has great potential for skin tissue engineering. Adhesive hydrogels based on polydopamine (PDA) have become the most popular in the biomedical field; however, integrating multiple properties on a single adhesive hydrogel remains a challenge. Here, inspired by the chemistry of mussels, we developed PDA-sodium alginate-polyacrylamide (PDA-SA-PAM)-based hydrogels with multiple physiological and biological properties for skin tissue engineering applications. The hydrogels were prepared by alkali-induced polymerization of DA followed by complexation with SA in PAM networks. The chemical composition of the hydrogels was characterized by X-ray photoelectron spectroscopy. PDA-SA complexed chains were homogeneously dispersed in the PAM network and exhibited good elasticity and excellent mechanical properties, such as a compressive stress of 0.24 MPa at a compression strain of 70% for 0.4PDA-SA-PAM. The adhesive hydrogel also maintained a highly interconnected porous structure (?94% porosity) along with PDA microfibrils. The hydrogel possesses outstanding swelling and biodegradability properties. Owing to the presence of the PDA-SA complex in the PAM network, the hydrogels show good adhesion to various substrates (plastic, skin, glass, computer screens, and leaves); for example, the adhesive strength of the 0.4PDA-SA-PAM to porcine skin was 24.5 kPa. The adhesive component of the PDA-SA chains in the PAM network significantly improves the cell proliferation, cell attachment, cell spreading, and functional expression of human skin fibroblasts (CCD-986sk) and keratinocytes. Moreover, the PDA chains exhibited good hemostatic properties, resulting in rapid blood coagulation. Considering their excellent cell affinity, and rapid blood coagulation ability, these mussel-inspired hydrogels have substantial potential for skin tissue engineering applications.