Chitosan-based dressings loaded with neurotensin--an efficient strategy to improve early diabetic wound healing

Acta Biomater. 2014 Feb;10(2):843-57. doi: 10.1016/j.actbio.2013.09.040. Epub 2013 Oct 10.


One important complication of diabetes mellitus is chronic, non-healing diabetic foot ulcers (DFUs). This study aims to develop and use dressings based on chitosan derivatives for the sustained delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. Three different derivatives, namely N-carboxymethyl chitosan, 5-methyl pyrrolidinone chitosan (MPC) and N-succinyl chitosan, are presented as potential biomaterials for wound healing applications. Our results show that MPC has the best fluid handling capacity and delivery profile, also being non-toxic to Raw 264.7 and HaCaT cells. NT-loaded and non-loaded MPC dressings were applied to control/diabetic wounds to evaluate their in vitro/in vivo performance. The results show that the former induced more rapid healing (50% wound area reduction) in the early phases of wound healing in diabetic mice. A NT-loaded MPC foam also reduced expression of the inflammatory cytokine TNF-α (P<0.001) and decreased the amount of inflammatory infiltrate on day 3. On day 10 MMP-9 was reduced in diabetic skin (P<0.001), significantly increasing fibroblast migration and collagen (COL1A1, COL1A2 and COL3A1) expression and deposition. These results suggest that MPC-based dressings may work as an effective support for sustained NT release to reduce DFUs.

Keywords: Chitosan derivatives; Diabetic foot ulcers; Neurotensin; Wound dressings; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bandages*
  • Biocompatible Materials / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chitosan / analogs & derivatives
  • Chitosan / chemical synthesis
  • Chitosan / chemistry*
  • Collagen / genetics
  • Collagen / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetic Foot / pathology*
  • Gene Expression Profiling
  • Glutathione / metabolism
  • Humans
  • Hydroxyproline / metabolism
  • Inflammation / pathology
  • Kinetics
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Neurotensin / pharmacology*
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry
  • Skin / drug effects
  • Skin / pathology
  • Steam
  • Wound Healing / drug effects*


  • Biocompatible Materials
  • Cytokines
  • N-succinyl-chitosan
  • Pyrrolidinones
  • Steam
  • carboxymethyl-chitosan
  • methylpyrrolidinone chitosan
  • Neurotensin
  • Collagen
  • Chitosan
  • Matrix Metalloproteinase 9
  • Glutathione
  • Hydroxyproline