1. Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease.
- Author
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Hong L, Chen G, Cai Z, Liu H, Zhang C, Wang F, Xiao Z, Zhong J, Wang L, Wang Z, and Cui W
- Subjects
- Animals, Biocompatible Materials administration & dosage, Biocompatible Materials therapeutic use, Disease Models, Animal, Drug Liberation, Injections, Mice, Heparin administration & dosage, Heparin therapeutic use, Hydrogels administration & dosage, Hydrogels therapeutic use, Inflammation therapy, Inflammatory Bowel Diseases therapy, Serum Albumin, Bovine administration & dosage, Serum Albumin, Bovine therapeutic use, Thrombosis therapy
- Abstract
Emerging evidence indicates that a vicious cycle between inflammation and microthrombosis catalyzes the pathogenesis of inflammatory bowel disease (IBD). Over-stimulated inflammation triggers a coagulation cascade and leads to microthrombosis, which further complicates the injury through tissue hypoxia and ischemia. Herein, an injectable protein hydrogel with anti-thrombosis and anti-inflammation competency is developed to impede this cycle, cross-linked by silver ion mediated metal-ligand coordination and electronic interaction with sulfhydryl functionalized bovine serum albumin and heparin, respectively. The ex vivo experiments show that the hydrogel, HEP-Ag-BSA, exhibits excellent self-healing ability, injectability, biocompatibility, and sustained drug release. HEP-Ag-BSA also demonstrates anti-coagulation and anti-inflammation abilities via coagulation analysis and lipopolysaccharide stimulation assay. The in vivo imaging confirms the longer retention time of HEP-Ag-BSA at inflammatory sites than in normal mucosa owing to electrostatic interactions. The in vivo study applying a mouse model with colitis also reveals that HEP-Ag-BSA can robustly inhibit inflammatory microthrombosis with reduced bleeding risk. This versatile protein hydrogel platform can definitively hinder the "inflammation and microthrombosis" cycle, providing a novel integrated approach against IBD., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
- Published
- 2022
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