All-aqueous microfluidic fabrication of calcium alginate/alkylated chitosan core-shell microparticles with time-sequential functions for promoting whole-stage wound healing

Wound healing comprises a series of complex physiological processes, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Designing new functional biomaterials by biological macromolecules with tailored therapeutic effects to precisely match the unique requirements of each stage is cherished but rarely discussed. Here, we employ all-aqueous microfluidics to fabricate multifunctional core-shell microparticles aimed at promoting whole-stage wound healing. These microparticles feature a core comprising calcium alginate, cellulose nanocrystals and epidermal growth factor, surrounded by a shell made of alkylated chitosan, alginate, and ciprofloxacin (EGF + CNC@Ca-ALG/CIP@ACS core-shell microparticles, D-CSMP). Response surface methodology (RSM) with a combination of central composite rotatable design (CCRD) is used to meticulously optimize the fabrication processes, endowing the resulting D-CSMP with superior capabilities for efficiently encapsulating and controlled releasing CIP and EGF tailored to each stage aligning the healing timeline. The developed D-CSMP demonstrate notable time-sequential functionalities, including promoting blood coagulation, enhancing hemostasis, and exerting antibacterial effects. Furthermore, in a skin injury model, D-CSMP significantly expedite and enhance the chronic wound healing process. In conclusion, our core-shell microparticles with notable time-sequential functions present a versatile and robust approach for wound treatment and related biomedical applications.