Abstract

The Asherman’s syndrome, also known as intrauterine adhesion, often follows endometrium injuries resulting from dilation and curettage, hysteroscopic resection, and myomectomy as well as infection. It often leads to scarring formation and female infertility. Pathological changes mainly include gland atrophy, lack of vascular stromal tissues and hypoxia and anemia microenvironment in the adhesion areas. Surgical intervention, hormone therapy and intrauterine device implantation are the present clinical treatments for Asherman’s syndrome. However, they do not result in functional endometrium recovery or pregnancy rate improvement. Instead, an increasing number of researches have paid attention to the reconstruction of biomimetic endometrium interfaces with advanced tissue engineering technology in recent decades. From micro-scale cell sheet engineering and cell-seeded biological scaffolds to nano-scale extracellular vesicles and bioactive molecule delivery, biomimetic endometrium interfaces not only recreate physiological multi-layered structures but also restore an appropriate nutritional microenvironment by increasing vascularization and reducing immune responses. This review comprehensively discusses the advances in the application of novel biocompatible functionalized endometrium interface scaffolds for uterine tissue regeneration in female infertility.

Highlights

  • Secondary infertility is the most common type of female infertility worldwide, often because of endometrium injuries and subsequent intrauterine adhesion (IUA)

  • The findings indicated implantable adiposederived stem cells (ADSC) sheets attached closely to the injured uterine and facilitated endometrium repair by providing a biomimetic trophic support that was vital for cell proliferation

  • The findings showed a 31.2% improvement of pregnancy rate in the application of collagen binding domain (CBD)/vascular endothelial growth factor (VEGF) collagen (50.0%) compared with local VEGF injection only (18.8%)

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Summary

INTRODUCTION

Secondary infertility is the most common type of female infertility worldwide, often because of endometrium injuries and subsequent intrauterine adhesion (IUA). OMEC, oral mucosal epithelial cell; ADSC, adipose-derived stem cell; dEMSC, decidualized endometrial stromal cell; En-PSC, endometrial perivascular cell; CYR61, cysteine-rich angiogenic inducer 61; BMSC, bone marrow mesenchymal stem cell; BMNC, bone marrow mononuclear cell; UCMSC, umbilical cord derived mesenchymal stem cell; hESC, human embryonic stem cell; CBD, collagen binding domain; bFGF, basic fibroblast growth factor; MMP, matrix metalloprotein; ECM, extracellular matrix; mTOR, mammalian target of rapamycin; ERK 1/2, extracellular regulated protein kinases 1/2; SDS, sodium dodecyl sulfate; SD, Sprague Dawley. The functionalized nanoscaffold delivered SDF-1α from SF-BC membrane carrier and induced uterine cell migration in vitro and increased endometrium thickness and number of fetuses They explained the effects of functionalized BC scaffold as it improved migration and regeneration of glandular epithelial cells, which were vital for decidualization, implantation, and embryo development. Lin et al (2012) loaded CBD/VEGF on the collagen scaffold for improving angiogenesis and endometrium re-epithelialization They compared different release manners of VEGF, including CBD and native injection, in the regeneration of full-thickness injury of rat uterus. These researches indicate that decellularized biomaterials are helpful to functional uterus regeneration, due to their biocompatibility, regulation of cell survival and homing, and topological support (Table 1)

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