Injectable bioactive akermanite/alginate composite hydrogels for in situ skin tissue engineering

Abstract

In situ tissue engineering holds great promise in regenerative medicine owing to the utilization of the body's own regenerative capacity via recruiting host endogenous stem cells or tissue-specific progenitor cells to the site of injury. In this study, an injectable bioactive akermanite/alginate composite hydrogel was prepared for in situ tissue engineering using an akermanite bioceramic as a bioactive cross-linking component to provide bioactive ions such as Ca, Mg and Si. These bioactive ions on the one hand cross-link alginate to form injectable hydrogels in the presence of acidic amino acids and on the other hand function as bioactive stimuli to activate the wound healing process. The bioactive hydrogel exhibits specific activity in regulating cell behavior such as migration, proliferation and differentiation both in vitro and in vivo. Most interestingly, using a chronic wound healing model, we demonstrated for the first time that the composite hydrogel significantly enhances the healing of chronic wounds by recruiting stem cells, stimulating cell proliferation, and enhancing blood vessel formation and re-epithelialization. Our results indicate that the injectable bioactive composite hydrogels act as in situ tissue engineering scaffolds to stimulate the regeneration of skin tissue, and utilizing the interaction between the bioactive bioceramics and biopolymers, in which bioceramics function as both cross-linking agents and bioactive factors, is a versatile strategy for designing multifunctional bioactive biomaterials for wound healing and tissue engineering applications.