All-aqueous microfluidic printing of multifunctional bioactive microfibers promote whole-stage wound healing

Abstract

Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.