Extracellular matrix hydrogels for endometrial regeneration
File(s)
Author(s)
Chan, Maxine
Type
Thesis
Abstract
Intrauterine scarring is an important cause of infertility and other adverse pregnancy outcomes. Current treatments do not specifically address the pathological process of fibrosis and are not highly effective, particularly when it comes to functional endometrial regeneration. This thesis explored a biomaterials approach to preventing intrauterine adhesions and hypothesised that an endometrial ECM hydrogel has favourable bioactive properties to prevent fibrosis and to promote endometrial repair. A new protocol for decellularising porcine endometrial ECM was described and the decellularised ECM was then comprehensively characterised using various biomolecular tools to demonstrate the preservation of important ECM proteins and matrix-bound nanovesicles, with exosome-like properties. An injectable and sprayable, thermo-responsive hydrogel was made from decellularised endometrial ECM, with gelation properties that made it suitable for in vivo applications. Using various in vitro assays, endometrial ECM hydrogel was demonstrated to be compatible with endometrial cells, improve angiogenesis and possess immunomodulatory properties. It was also capable of mitigating the effect of TGF-1 in an in vitro endometrial fibrosis experiment. A reliable mouse model of intrauterine fibrosis was developed, using ethanol to induce endometrial damage. Applying endometrial ECM hydrogel in this model demonstrated primary prevention of endometrial damage in 60% of the ECM-treated group. ECM hydrogel treatment also significantly reduced the gene expression of Collagen I in the ethanol-injured uterine horns. These results demonstrated the favourable effect of endometrial ECM hydrogel for limiting intrauterine fibrosis and will pave the way for further studies on secondary prevention of scarring and fertility preservation.
Version
Open Access
Date Issued
2022-05-30
Date Awarded
01/03/2023
Advisor
Stevens, Molly
Smith, J Richard
Saso, Srdjan
Sponsor
Wellbeing of Women (Charity)
Grant Number
RG2123
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)