Biological testing of chitosan-collagen-based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection-related stenosis in oesophagus

Cell Prolif. 2021 Mar;54(3):e13004. doi: 10.1111/cpr.13004. Epub 2021 Feb 4.

Abstract

Objectives: Endoscopic submucosal dissection (ESD), a preferential approach for early oesophageal neoplasms, inevitably results in oesophageal strictures in patients. Clinical use of glucocorticoids through submucosal injection is beneficial for inhibiting oesophageal stricture following injury; however, it also has limitations, such as dose loss and perforation. Hence, alternatives to glucocorticoid therapy should be developed.

Methods: A novel porous composite scaffold, ChCo-TAMS, composed of chitosan, collagen-I and triamcinolone acetonide (TA) loaded into poly (lactic-co-glycolic) acid (PLGA) microspheres (TAMS), was successfully constructed and subjected to biological testing to ameliorate oesophageal ESD-related stenosis.

Results: The synthesized biomaterials displayed unique properties in inhibiting the activation of macrophages, chemokine-mediated cell recruitment and fibrogenesis of fibroblasts. Further application of the scaffolds in the rat dermal defect and porcine oesophageal ESD model showed that these novel scaffolds played a robust role in inhibiting wound contracture and oesophageal ESD strictures.

Conclusions: The developed composite scaffolds provide a promising clinical medical device for the prevention of post-operative oesophageal stricture.

Keywords: ESD; microsphere; scaffold; stricture; triamcinolone acetonide.

MeSH terms

  • Animals
  • Biocompatible Materials / metabolism
  • Chitosan / metabolism
  • Chitosan / pharmacology*
  • Collagen / drug effects*
  • Collagen / metabolism
  • Constriction, Pathologic / etiology
  • Constriction, Pathologic / pathology*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophageal Stenosis / drug therapy*
  • Esophageal Stenosis / prevention & control
  • Mice
  • Microspheres
  • Triamcinolone / metabolism
  • Triamcinolone Acetonide / administration & dosage
  • Triamcinolone Acetonide / pharmacology

Substances

  • Biocompatible Materials
  • Triamcinolone
  • Collagen
  • Chitosan
  • Triamcinolone Acetonide