The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats†

Miki, Fumie; Maruyama, Tetsuo; Miyazaki, Kohji; Takao, Tomoka; Yoshimasa, Yushi; Katakura, Satomi; Hihara, Hanako; Uchida, Sayaka; Masuda, H.; Uchida, Hiroshi; Nagai, Toshihiro; Shibata, Shinsuke; Tanaka, Mamoru

doi:10.1093/biolre/ioz004

Cited by 34 publications

(31 citation statements)

References 37 publications

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“…In addition, the excellent biomechanical properties guaranteed uterine regeneration for a long term in vivo. Miki et al (2019) found orientation in the smooth muscle cells and ECM was a vital factor of correct tissue topology and functional uterine regeneration by a decellularized scaffold from 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).…”

Section: Decellularized Biomimetic Scaffolds For Severe Uterine Injurmentioning

confidence: 87%

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

Han

2020

Front. Bioeng. Biotechnol.

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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 nanoscale 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.

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Section: Decellularized Biomimetic Scaffolds For Severe Uterine Injurmentioning

confidence: 87%

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

Han

2020

Front. Bioeng. Biotechnol.

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“…They also prepared an ECM scaffold from rat small intestine, but, unlike the uterine scaffold, it had no supportive capacity. These results collectively indicate that the ECM and architecture of the uterine scaffold retain functionality and determine the orientation and topology of regenerated uterine tissue [ 83 ]. Santoso et al [ 84 ] and Hellström et al [ 86 , 87 ] independently demonstrated that uterine scaffolds prepared by different protocols had similar capacities as supportive materials to regenerate uterine tissue in rats.…”

Section: Uterine Tissue Engineeringmentioning

confidence: 98%

“…Decellularization and recellularization techniques for regeneration of the uterus have emerged since 2013 as shown in Table 2 [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98].…”

Section: Decellularization and Recellularization Strategymentioning

confidence: 99%

“…Moreover, placement of an acellular scaffold onto a partially excised rat uterus promoted recellularization and regeneration of uterine tissues and achievement of pregnancy nearly comparable to that in an intact uterus [ 82 ]. The same group showed that disoriented placement of the scaffold onto a partially excised rat uterus resulted in regeneration of the uterine tissue but with aberrant structures including ectopic location of glands and an abnormal lining of smooth muscle layers [ 83 ]. They also prepared an ECM scaffold from rat small intestine, but, unlike the uterine scaffold, it had no supportive capacity.…”

Section: Uterine Tissue Engineeringmentioning

confidence: 99%

“…Furthermore, the use of animals larger than rats and mice, ideally primates, would be better for the characterization and validation of a decellularized scaffold in terms of clinical applications. On the other hand, compared to synthetic or natural materials, the ECM and architecture preserved in a decellularized scaffold may determine the orientation and topology of the regenerated uterine tissue [ 83 ]. Therefore, in clinical testing of bioengineering methods, it would be preferable if the decellularized scaffold were prepared from a human uterus followed by transplantation in a proper orientation to fabricate the complex structure of the uterus.…”

Section: Uterine Tissue Engineeringmentioning

confidence: 99%

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Bioengineering of the Uterus

Yoshimasa

Maruyama

2021

Reprod. Sci.

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Impairment of uterine structure and function causes infertility, pregnancy loss, and perinatal complications in humans. Some types of uterine impairments such as Asherman’s syndrome, also known as uterine synechiae, can be treated medically and surgically in a standard clinical setting, but absolute defects of uterine function or structure cannot be cured by conventional approaches. To overcome such hurdles, partial or whole regeneration and reconstruction of the uterus have recently emerged as new therapeutic strategies. Transplantation of the whole uterus into patients with uterine agenesis results in the successful birth of children. However, it remains an experimental treatment with numerous difficulties such as the need for continuous and long-term use of immunosuppressive drugs until a live birth is achieved. Thus, the generation of the uterus by tissue engineering technologies has become an alternative but indispensable therapeutic strategy to treat patients without a functional or well-structured uterus. For the past 20 years, the bioengineering of the uterus has been studied intensively in animal models, providing the basis for clinical applications. A variety of templates and scaffolds made from natural biomaterials, synthetic materials, or decellularized matrices have been characterized to efficiently generate the uterus in a manner similar to the bioengineering of other organs and tissues. The goal of this review is to provide a comprehensive overview and perspectives of uterine bioengineering focusing on the type, preparation, and characteristics of the currently available scaffolds.

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Strategies for managing Asherman's syndrome and endometrial atrophy: Since the classical experimental models to the new bioengineering approach

Miguel-Gómez

Romeu

Pellicer

et al. 2021

Molecular Reproduction Devel

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Endometrial function is essential for embryo implantation and pregnancy, but managing endometrial thickness that is too thin to support pregnancy or an endometrium of compromised functionality due to intrauterine adhesions is an ongoing challenge in reproductive medicine. Here, we review current and emerging therapeutic and experimental options for endometrial regeneration with a focus on animal models used to study solutions for Asherman's syndrome and endometrial atrophy, which both involve a damaged endometrium. A review of existing literature was performed that confirmed the lack of consensus on endometrial therapeutic options, though promising new alternatives have emerged in recent years (platelet-rich plasma, exosomes derived from stem cells, bioengineering-based techniques, endometrial organoids, among others). In the future, basic research using established experimental models of endometrial pathologies (combined with new high-tech solutions) and human clinical trials with large population sizes are needed to evaluate these emerging and new endometrial therapies.

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The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats†

Cited by 34 publications

References 37 publications

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

Bioengineering of the Uterus

Strategies for managing Asherman's syndrome and endometrial atrophy: Since the classical experimental models to the new bioengineering approach

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