KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats.

Abstract

OBJECTIVE:

The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats.

RESEARCH DESIGN AND METHODS:

In this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0.

RESULTS:

A 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31.

CONCLUSIONS:

A KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.

• Authors: Xuanxin Yang, Rongshuai Yang, Min Chen, Qingde Zhou, Yingying Zheng, Chao Lu, Jianing Bi, Wenzhe Sun, Tongzhou Huang, Lijia Li, Jianxiang Gong, Xiaokun Li, Qi Hui, Xiaojie Wang
• Journal: BMJ open diabetes research & care (BMJ Open Diabetes Res Care) Vol. 8 Issue 1 (05 2020) ISSN: 2052-4897 [Electronic] England
• PMID: 32434772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Fibroblast Growth Factor 10
• Hydrogels
• Vascular Endothelial Growth Factor A
• fibroblast growth factor 21
• Poloxamer
• Fibroblast Growth Factors

Topics

• Animals
• Cell Proliferation
• Diabetes Mellitus, Experimental (drug therapy)
• Fibroblast Growth Factor 10
• Fibroblast Growth Factors
• Homeostasis
• Humans
• Hydrogels
• Inflammation (drug therapy)
• Poloxamer
• Rats
• Vascular Endothelial Growth Factor A
• Wound Healing