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

FASEB J. 2019 Sep;33(9):9858-9870. doi: 10.1096/fj.201802600RR. Epub 2019 Jun 5.

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.

Keywords: T2DM; biomaterial; skin wound; sustained release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Experimental*
  • Dosage Forms
  • Drug Liberation
  • Fibroblast Growth Factors / administration & dosage
  • Fibroblast Growth Factors / chemistry
  • Fibroblast Growth Factors / pharmacology*
  • Glucose Tolerance Test
  • Heparin / chemistry*
  • Humans
  • Hydrogels / chemistry*
  • Insulin
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Poloxamer / chemistry*
  • Recombinant Proteins
  • Wound Healing / drug effects*

Substances

  • Blood Glucose
  • Dosage Forms
  • Hydrogels
  • Insulin
  • Recombinant Proteins
  • fibroblast growth factor 21
  • Poloxamer
  • Fibroblast Growth Factors
  • Heparin