Future Challenges and Opportunities of Extracellular Matrix Hydrogels in Female Reproductive Medicine

Abstract

Bioengineering and reproductive medicine have progressed shoulder to shoulder for several decades. A key point of overlap is the development and clinical translation of technologies to support reproductive health, e.g., scaffold-free constructs, polymeric scaffolds, bioprinting or microfluidics, and hydrogels. Hydrogels are the focus of intense study, and those that are derived from the extracellular matrix (ECM) of reproductive tissues and organs are emerging as promising new players given their results in pre-clinical models. This literature review addresses the recent advances in the use of organ-specific ECM hydrogels in reproductive medicine, considering the entire female reproductive tract. We discuss in-depth papers describing the development of ECM hydrogels, their use in in vitro models, and their in vivo application in preclinical studies. We also summarize the functions of hydrogels, including as grafts, carriers for cell transplantation, or drug depots, and present the potential and possible scope for use of ECM hydrogels in the near future based on recent scientific advances.

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

“…Alternatively, when the hUC-PRP was loaded into the EndoECM hydrogel, molecular alterations led to improved tissue regeneration, but the injured endometrium was not completely restored, preventing the mice from achieving similar pregnancy rates to the sham group. We suspect these findings are related to the low concentration of hUC-PRP mixed with the EndoECM hydrogel (15% v/v; which had previously been described as sufficient in the pancreas ( Zhang et al , 2020a ) and other tissues ( Francés-Herrero et al , 2022b ), but might not be adequate in the endometrium) and suggest testing higher concentrations of hUC-PRP in future investigations. Interestingly, we found embryo weight at 2 weeks of gestation (E14.5) was similar with respect to control embryos, indicating the treatments did not alter early embryo development.…”

“…Hydrogels are by far the most prominently used bioengineering strategy for female reproductive medicine ( Francés-Herrero et al , 2022a ) and are composed of hydrophilic polymeric networks, which can deliver controlled drug-release into target wounds ( Narayanaswamy and Torchilin, 2019 ). Since ECM-based hydrogels are proven to mimic the physicochemical properties of the tissue of origin, we hypothesized they could provide the perfect environment for tissue regeneration ( Francés-Herrero et al , 2022b ). Due to their spatiotemporal control over the mobilization of therapeutic agents into the tissue of interest, hydrogels loaded with peripheral blood PRP have previously been demonstrated to be highly effective therapeutic strategies, promoting tissue regeneration, wound healing efficiency, vascularization and suitable biocompatibility ( Xu et al , 2017 ; Zhang et al , 2020a , b , 2021 ).…”

A Review on Biomedical Application of Polysaccharide-Based Hydrogels with a Focus on Drug Delivery Systems

“…Clotrimazole, an anti-fungal drug used in the form of hydrogel to manage vaginitis, can be considered a perfectly matched example in this field to clarify the importance of hydrogels for the vaginal DDS [93]. Regarding this topic, Buckenmeyer et al studied premature ovarian failure via extracellular matrix (ECM) ovarian hydrogels as a follicle carrier, which is schematically represented in Figure 4 [94,95]. This figure represents the strategies for regenerating the intervertebral disc using extracellular matrix and decellularized tissue-based extracellular matrix (ECM).…”

Human Umbilical Cord-Based Therapeutics: Stem Cells and Blood Derivatives for Female Reproductive Medicine

“…Thus far, only collagen-derived scaffolds have been applied in clinical trials, for patients affected by POI [200] and AS [67,217]. However, tissue-specific hydrogel scaffolds that mimic the target microenvironment are quickly emerging as alternatives, since they potentiate the restorative effects [247], as has been demonstrated with murine models of AS [230].…”