Electrospun SF/PHBV nanofibers loaded with berberine as a bioactive wound dressing: Accelerating diabetic wound healing and alleviating hypertrophic scar
Hongyu Lv, Siyuan Wang, Ming He, Xue Y. Zhu, Peng He, Ruochen Sun, Zitong Jia, Ziming Wang, Wenwen Zhao, Zhangfeng Zhong, Yantao Han
Abstract
The study of BBR-loaded SF/PHBV nanofibrous membrane on wound healing in diabetic mice and the therapeutic effect of hypertrophic scar in rabbits. • Berberine (BBR), the active ingredient of Chinese medicine, was loaded in the SF/PHBV nanofibers (namely SF/PHBV-BBR) to perform multiple pharmacological properties. • SF/PHBV-BBR accelerated diabetic wound healing by anti-inflammatory and anti-oxidative activities in diabetic mouse model. • SF/PHBV-BBR inhibited the scar hyperplasia through the TGF-β1/Smad3 signaling pathway in the rabbit ear model. The development of innovative wound dressings that can accelerate diabetic wound healing and alleviate hypertrophic scar has aroused intensive attraction in the clinics. In this study, the nanofibrous wound dressings constructed with a blend of silk fibroin (SF) and poly-3-hydroxybutyric acid-co-3-hydroxyvaleric acid (PHBV) were designed and fabricated. Meanwhile, berberine (BBR) were loaded in the SF/PHBV nanofibers to enhance the pharmacological effects. Firstly, material characterisation and biological characteristics of SF/PHBV-BBR dressings were investigated. The addition of BBR didn’t change the mechanical properties and biocompatibility of SF/PHBV nanofiber dressings. Then in vitro experiment proved that SF/PHBV-BBR nanofiber dressings obviously decreased the releases of inflammatory factors TNF-ɑ and IL-6, inhibited inflammatory proteins COX-2 and iNOS expression, and also suppressed oxidative stress responses of activated macrophages. Subsequently, in vivo study showed that SF/PHBV-BBR nanofiber dressings with high dose of BBR significantly promoted the healing of diabetic wounds in mice by significantly enhancing wound closure rates, accelerating angiogenesis, and improving collagen matrix deposition. Additionally, SF/PHBV-BBR obviously alleviated scar hyperplasia in rabbit by inhibiting fibroblast activation mediated by transforming growth factor-β1 (TGF-β1)/Smad3 pathway. Our study offered a promising alternative dressing materials for the treatment of hard-to-heal diabetic wounds and hypertrophic scars.