Bioengineering of the Uterus

Abstract

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.

Keywords: Endometrium; Scaffold; Stem cells; Tissue engineering; Uterus.

Fig. 1

Therapeutic strategies for bioengineering of the uterus. Currently, scaffolds for the regeneration of the uterus are divided into two categories: (1) a decellularized scaffold that is prepared from the uterus or uterine tissue derived from the donor through removal of cellular components by single or combined physical, chemical, and enzymatic treatments; (2) synthetic or natural materials made of collagen, gelatin, fibrin, silk sponge, poly(glycolic acid), poly(glycerol sebacate), and poly(lactic-co-glycolic acid) through condensation, polymerization, and crosslinking. To regenerate the uterus, these scaffolds with or without the addition of various types of cells including uterine cells and mesenchymal stem cells are implanted directly into the defective uterus. Alternatively, the cells alone are transplanted directly into the defective uterus. UtCs, uterine cells; MSCs, mesenchymal stem cells; ESCs, embryonic stem cells; iPSCs, induced pluripotent stem cells