Squid Suckerin-Spider Silk Fusion Protein Hydrogel for Stem Cell-Secretome Delivery in Chronic Wounds

The squid sucker ring teeth, used in tandem with the suckers on the squid’s tentacles to capture prey, is comprised of mainly suckerin, a protein material. Squid suckerin is a promising biopolymer for wound dressings due to its biocompatibility, antibacterial properties, and its ability to form gels/films of varying mechanical properties. However, issues such as low recombinant solubility and the requirement of harsh photochemical means for gel/film formation hinders suckerin’s suitability for encapsulation and delivery of stem cell-secretome, which is a bioactive yet sensitive therapeutic shown to overcome persistent wound inflammation and accelerate wound healing. Via bioinspired design, we developed a novel squid suckerin-spider silk fusion protein hydrogel, where the fusion of key spider silk sequences conferred high solubility and heat-induced gelation properties that enabled encapsulation of secretome without denaturation. The protein hydrogel is capable of long-term delivery of secretome via protein-protein interaction. Additionally, due to its modular design, we incorporated cell adhesion peptides to promote biocompatibility of the hydrogel. In our results, we demonstrate the secretome-loaded hydrogel potential for clinical use via accelerated healing of excisional chronic wounds <i>in vivo</i>.