A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes

Authors：Wei, Shikun; Xu, Pengcheng; Yao, Zexin; Cui, Xiao; Lei, Xiaoxuan; Li, Linlin; Dong, Yunqing; Zhu, Weidong; Guo, Rui^*; Cheng, Biao^*

Source：Acta Biomaterialia, 2021, 124: 205-218.

DOI：10.1016/j.actbio.2021.01.046

• Antimicrobial peptide
• Platelet-rich plasma (PRP)
• Hydrogel
• Diabetic infected wound

Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains ( E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-alpha, IL-1 beta and IL-6), enhanced anti-inflammatory factors (TGF-beta 1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing. @@@ Statement of significance @@@ This research article prepares a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of PRP), thus promoting effectively wound healing. The hydrogel showed sustained-release AMP and grow factors capacity, obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and stimulative proliferation and migration of L929 fibroblast cells. In addition, the hydrogel could accelerate wound healing in a diabetic mouse infection and contribute to higher density of collagen deposition, lower bacterial number and balanced inflammatory infiltration. This study provided not only an effective repair hydrogel material for wounds, especially in major infected wounds and diabetic foot ulcers, but also developed an advanced method for PRP application.

• Institution
  广东省人民医院; 广东药学院; 南方医科大学