A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.