An alginate/poly(N-isopropylacrylamide)-based composite hydrogel dressing with stepwise delivery of drug and growth factor for wound repair

摘要

Anti-inflammation and angiogenesis play an essential role in wound healing. In this study, we developed a composite hydrogel dressing with stepwise delivery of diclofenac sodium (DS) and basic fibroblast growth factor (bFGF) in the inflammation stage and new tissue formation stage respectively for wound repair. Sodium alginate (SA) crosslinked by calcium ion acted as the continuous phase, and thermosensitive bFGF-loaded poly(N-iso-propylacrylamide) nanogels (pNIPAM NGs, LCST1 similar to 33 degrees C) and DS-loaded p(N-isopropylacrylamide-co-acrylic acid) nanogels [p(NIPAM-co-AA) NGs, LCST2 similar to 40 degrees C] acted as the dispersed phase. The synthesized SA/bFGF@pNIPAM/DS@p(NIPAM-co-AA) hydrogel presented a desirable storage modulus of similar to 4500 Pa, a high water equilibrium swelling ratio of similar to 90, an appropriate water vapor transmission rate of similar to 2300 g/m(2)/day, and nontoxicity to human skin fibroblasts. The in vitro thermosensitive cargo delivery of this hydrogel showed that 92% of DS was sustainably delivered at 37 degrees C within the early three days mimicking the inflammation stage, while 80% of bFGF was controlled released at 25 degrees C within the later eight days mimicking new tissue formation stage. The in vivo wound healing of rats showed that this composite hydrogel presented a better healing effect with a wound contraction of 96% at 14 d, less inflammation and higher angiogenesis, than all control groups. These findings indicate SA/bFGF@pNIPAM/DS@p(NIPAM-co-AA) composite hydrogel is a potential dressing for wound repair.