In situ hydrogel dressing loaded with heparin and basic fibroblast growth factor for accelerating wound healing in rat

• Published in: Materials Science & Engineering C 2020-11, Vol.116, p.111169-111169, Article 111169
• Main Authors: Peng, Jia, Zhao, Hui, Tu, Chengzhao, Xu, Zeqin, Ye, Lin, Zhao, Liang, Gu, Zongheng, Zhao, Dong, Zhang, Jie, Feng, Zengguo
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Bandages; bFGF; Cell proliferation; Dithiothreitol; Drug delivery; Encapsulation; Enzyme-linked immunosorbent assay; Epidermis; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - pharmacology; Fibroblasts; Growth factors; Heparin; Heparin - pharmacology; Hydrogel dressing; Hydrogels; Hydrogels - pharmacology; Immunofluorescence; In vitro methods and tests; In vivo methods and tests; Materials science; Polyethylene glycol; Rats; Staining; Transforming growth factor-b; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Wound Healing
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.111169

In order to accelerate the healing of chronic wound, a hydrogel dressing encapsulating with heparin and basic fibroblast growth factor is prepared by the Michael addition of 4-arm acrylated polyethylene glycol and dithiothreitol. As-prepared hydrogel dressing can combine the advantages of wet healing theory and exogenous growth factor supplement. Furthermore, the encapsulated heparin can play a role in diminishing inflammation and accelerating wound healing in addition to its well-known function of stabilizing basic fibroblast growth factor. In vitro release test shows the hydrogel network is able to sustainably release basic fibroblast growth factor within 10 days by the regulation of heparin, while released growth factor can significantly promote fibroblast's proliferation in vitro. Moreover, the wound healing in rat shows that as-prepared hydrogel dressing could accelerate wound healing in vivo much more effectively compared with blank hydrogel dressing and negative control. Hematoxylin-eosin and Masson's Trichrome staining exhibit the formation of complete and uniform epidermis. Immunohistochemical staining exhibits heparin can help hydrogel dressing to possess low inflammation in early stage, which is beneficial for accelerating wound healing as well as preventing the production of scar tissue. The enzyme-linked immunosorbent assay results demonstrate the exogenous bFGF in hydrogel can significantly upgrade the expressing of vascular endothelial growth factor and transforming growth factor-β in wound site, which indicate better angiogenesis, and better on-site cell proliferation in wound site, respectively. Those results are further demonstrated by immunohistochemical and immunofluorescence staining. Consequently, as-prepared hydrogel dressing shows promising potential to perform better therapy efficacy in clinic for accelerating wound healing. [Display omitted] •As-prepared hydrogel dressing can combine the advantages of wet healing theory and exogenous bFGF treatment.•It was found that addition of bFGF can upgrade the expression of VEGF and TGF-β.•Heparin can not only stabilize bFGF activity and sustainably release it in vivo, but also reduce inflammation.•As-prepared hydrogel dressing can significantly accelerate wound healing in rat model.