Heparin‐poloxamer hydrogel‐encapsulated rhFGF21 enhances wound healing in diabetic mice

Abstract

Wound healing, especially for diabetic wounds, is a lengthy and complicated process involving interactions and responses at the protein, cell, and tissue levels. Loading of growth factors into a hydrogel to construct a sustained‐release system is considered a promising approach to improve wound healing. The present study investigates the effect of thermosensitive heparin‐poloxamer (HP) hydrogel–encapsulated recombinant human fibroblast growth factor 21 (rhFGF21) on wound healing in mice with streptozotocin‐induced diabetes mellitus. First, we studied the in vitro release of rhFGF21 from the rhFGF21‐HP coacervate. The results showed that HP might control the release of rhFGF21. Next, we examined the effect of rhFGF21‐HP on skin wound healing in diabetic mice. Our data showed that rhFGF21‐HP significantly improved wound closure; promoted granulation, collagen deposition, and re‐epithelialization; and enhanced the expression of CD31. Moreover, rhFGF21‐HP had obvious advantages in diabetic wound healing. Therefore, the results suggest that the rhFGF21‐HP hydrogel polymer plays an important role in skin wound healing. This work provides a suitable sustained‐release delivery system that can continuously release rhFGF21 and presents a promising therapeutic strategy for wound healing in patients with diabetes.—Liu, H., Zhao, Y., Zou, Y., Huang, W., Zhu, L., Liu, F., Wang, D., Guo, K., Hu, J., Chen, J., Ye, L., Li, X., Lin, L. Heparin‐poloxamer hydrogel–encapsulated rhFGF21 enhances wound healing in diabetic mice. FASEB J. 33, 9858–9870 (2019). http://www.fasebj.org

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

“…A mouse model of type 2 diabetes can be induced by a HFD and a low dose of STZ (Liu et al, 2019;Maremanda et al, 2020). In the present study, mice were fed with a HFD for 12 weeks prior to the injection of STZ.…”

“…Type 2 diabetes mellitus (T2D) was induced via the combination of a high-fat diet (HFD) and a low dose of streptozotocin (STZ) (Liu et al, 2019). Mice aged 6-7 weeks were fed a rodent HFD (in which 60% of calories were derived from fat, Research Diets, New Brunswick, NJ, United States) for 12 weeks, and body weight was measured once a week.…”

Biomimetic Hydrogels to Promote Wound Healing

“…To meet mechanical and bio-functional properties, external and internal stimuli can be incorporated into the hydrogels. Thermo-sensitive crosslinkers are usually utilized to control the hydrogel formation under physiological temperature through incorporation of PEG ( Liu et al, 2019 ) or poly-( N -isopropylacrylamide) ( Luckanagul et al, 2018 ). These thermo-sensitive hydrogels can be injected to form hydrogels in situ and to maintain sustained drug release profile.…”

Gene therapy in wound healing using nanotechnology

“…In addition to using heparin, which prolongs growth factors half‐life by binding to them, the coacervate also included synthetic cations to provide further protection from degradation. Similarly, Liu et al significantly improved wound closure, granulation, re‐epithelialization and collagen deposition through the delivery of recombinant human fibroblast growth factor using heparin‐poloxamer hydrogel 91 . Like other nanofiber structures, this provided a sustained and continuous release of growth factors and even increased CD31 expression, which indicates the presence of endothelial cells in blood vessels, and subsequently, angiogenesis.…”