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

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.