9.2.2.a. Natural Polymers
Existing macromolecules that are present in ECM constitute natural biomaterials. Collagen, gelatin, hydrogels made of hyaluronic acid, fibrin, glycosaminoglycans, alginate, Matrigel, silk, hydroxyapatite, and other substances are among them. These materials have particular benefits, such as mechanical and adhesion qualities similar to those of natural ECM. Table 1 illustrates the utilization of natural biomaterials possessing strong biocompatibility in several studies to develop scaffolds for uterine tissue engineering [98].
Collagen is used extensively in uterine tissue engineering studies because of its advantage in maintaining the biological and structural integrity of the extracellular matrix, and its high abundance, low antigenicity, and mostly on the fact that myometrium consists of collagen in high amounts. Shuong Hong Lü et al (2009) conducted a study with the help of bionics and studied how engineered uterine tissues (EUTs) can produce the same physiological environment as that of in-vivo endometrial layer. This study paved way to study uterine diseases and embryonic development though EUTs. In this study, smooth muscle cells were mixed with Collagen and Matrigel and seeded to give a stromal layer, which was studied further by seeding epithelial cells on it. Similarly, the smooth muscle cells were also mixed with Matrigel to form a layer, and then both stromal & epithelial cells were seeded on this layer. In the first technique, embryos were cultured and studied, which showed blastocysts development, but further studies must be done to investigate embryonic implantation in the EUTs [99].
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Recently, Mesenchymal Stem cells (MSCs) are being used as cell therapy and for tissue regeneration for the treatment of uterine diseases. MSCs can be categorized as coming from bone marrow, umbilical cord, adipose tissue, or human menstrual blood, depending on their cellular source. Because of their ease of collection, minimal immunogenicity, and high proliferative capacity, umbilical cord derived MSCs (UC-MSCs) have been viewed as a prospective source for cell-based therapy. Lijun Ding et al, transplanted bone marrow mesenchymal stem cells (BM-MSCs) on collagen scaffolds, to replace damaged endometrium in rat’s uterus. The collagen scaffolds were degradable, provided a 3D structure for proper adherence, proliferation, and migration without impairing the stem cell genes. This acts as a potential method to explore further to study embryonic development [100].
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Song et al experimented with the regeneration of uterine endometrium for cell replacement therapy by generating endometrium-like cells from human embryonic stem cells (hESCs) and seeded these on a collagen scaffold to replace damaged uterine tissue. The differentiation of the hESCs was induced by coculturing them with endometrial stromal cells, to which other cytokines such as epidermal growth factor, were added. The hESC-derived endometrial cells were then shifted to a collagen scaffold which was transplanted to an animal model (rat). It was observed that the hESC-derived cells survived and recovered the replacement of uterine horns in a rat with severe uterine damage [96].
Wanqing Ji. et. al have used human induced pluripotent stem cells derived from mesenchymal stem cells (hiMSC) and loaded it to a sodium alginate hydrogel and obtained scaffolds using 3D bioprinter. The hydrogel scaffolds obtained indicated permissive in-vitro living environment and high survival duration for hiMSCs when compared to in vivo conditions. They concluded that the hiMSC hydrogel scaffolds played an important role in repair and histological structure of a damaged endometrium and restoring the abilities to support embryos. Development of this multidisciplinary technology can effectively solve many problems in near future and may be administered to patients with endometrial injuries in the future [101,102].
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