Pitaya-inspired microcarrier/hydrogel composite for chronic wound healing: One-pot preparation, tailorable structures, and versatile functionalization

Development of hydrogel-based constructs that integrate active substances appears to be a promising direction for treating chronic wounds. However, their practical applications are not satisfied as expected and limited by cumbersome fabrication processes, high production costs, uncontrolled compositions, and lacking multiple functions into one platform. Herein, inspired by the structure of a pitaya, a microcarrier-embedded hydrogel-based construct is designed via one-pot microfluidic emulsification. The hydrogel matrix like the creamy white flesh of a pitaya is composed of snail mucus and alginate, possessing demanded bio-adhesion, bio-activity, and bio-compatibility. The embedded microcarriers like the small black seeds of a pitaya are composed of mesoporous silica nanoparticles and poly(lactic-co-glycolic acid), serving as an excellent device to control drug de-livery. Benefited from the emulsion manipulation ability of microfluidic system, the content ratio of embedded microcarriers in hydrogel matrix, and the respective compositions of embedded microcarriers and hydrogel matrix are all variable to adapt to the individualized treatment. Importantly, the pitaya-inspired microcarrier/ hydrogel composite (PMH) can be further functionalized by introducing specific actives into its hierarchical compartments. After encapsulating silver nanoparticles and angiogenic molecules into the hydrogel matrix and embedded microcarriers respectively, both in vitro and in vivo experiments demonstrate that PMH can prevent bacteria invasion, promote cell function, and accelerate wound healing under diabetic conditions with enhanced epidermis regeneration, collagen deposition, blood vessel formation, and skin function recovery. Collectively, taking advantages of its one-pot preparation, tailorable structures, and versatile functionalization, the broad application of PMH in chronic wound management and other biomedical fields is anticipated.