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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.

SUBMITTER: Frances-Herrero E

PROVIDER: S-EPMC8998701 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Francés-Herrero Emilio E Rodríguez-Eguren Adolfo A Gómez-Álvarez María M de Miguel-Gómez Lucía L Ferrero Hortensia H Cervelló Irene I

International journal of molecular sciences 20220329 7

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 thei ...[more]

PMID: 35409119

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Project description:The extracellular matrix (ECM) is a complex assembly of hundreds of proteins forming the architectural scaffold of multicellular organisms. In addition to its structural role, the ECM conveys signals orchestrating cellular phenotypes. Alterations of ECM composition, abundance, structure, or mechanics have been linked to diseases and disorders affecting all physiological systems, including fibrosis and cancer. Deciphering the protein composition of the ECM and how it changes in pathophysiological contexts is thus the first step toward understanding the roles of the ECM in health and disease and toward the development of therapeutic strategies to correct disease-causing ECM alterations. Potentially, the ECM also represents a vast, yet untapped reservoir of disease biomarkers. ECM proteins are characterized by unique biochemical properties that have hindered their study: they are large, heavily and uniquely posttranslationally modified, and highly insoluble. Overcoming these challenges, we and others have devised mass-spectrometry-based proteomic approaches to define the ECM composition, or "matrisome," of tissues. This first part of this review provides a historical overview of ECM proteomics research and presents the latest advances that now allow the profiling of the ECM of healthy and diseased tissues. The second part highlights recent examples illustrating how ECM proteomics has emerged as a powerful discovery pipeline to identify prognostic cancer biomarkers. The third part discusses remaining challenges limiting our ability to translate findings to clinical application and proposes approaches to overcome them. Lastly, the review introduces readers to resources available to facilitate the interpretation of ECM proteomics datasets. The ECM was once thought to be impenetrable. Mass spectrometry-based proteomics has proven to be a powerful tool to decode the ECM. In light of the progress made over the past decade, there are reasons to believe that the in-depth exploration of the matrisome is within reach and that we may soon witness the first translational application of ECM proteomics.

Project description:BackgroundMedical training through specialization and even subspecialization has contributed significantly to clinical excellence in treating single acute conditions. However, the needs of complex patients go beyond single diseases, and there is a need to identify a group of generalists who are able to deliver cost-effective, holistic care to patients with multiple comorbidities and multi-faceted needs. Community hospitals (CHs) are a critical part of Singapore's shift toward a community-centric care model as the population ages. Community Hospitals of the Future ("CHoF") represent a series of emerging conversations around approaches to reimagine and redesign care delivery in a CH setting in response to changing care needs.MethodsAn environmental scan in the CH landscape using semi-structured interviews was conducted with 26 senior management, management, and working-level staff from seven community hospitals in Singapore. This environmental scan aims to understand the current barriers and future opportunities for CHs; to guide how CHs would have to shift in terms of (i) care delivery and resourcing, (ii) information flow, and (iii) financing; and to conceptualize CHoF to meet the changing care needs in Singapore.FindingsThe analysis of all transcripts revealed four broad sections of themes: (i) current care delivery in CHs, (ii) current challenges of CHs, (iii) future opportunities, and (iv) challenges in reimagining CHs. An emerging theme regarding the current key performance indicators used also surfaced. Resource limitations and financing structure of CH surfaced as limitations to expanding its capability. However, room for expansion of CH roles tapping on the current expertise were acknowledged and shared.ConclusionWith the current issues of (i) rapidly aging population, (ii) specialist-centric healthcare system, and (iii) fragmentation of care ecosystem, there is a need to further understand how CHoF can be modeled to better tackle them. Therefore, several important questions have been devised to land us in a microscopic view on how to develop CHoF in the right constructs. Demographic changes, patient segmentation, service and regulatory parameters, patient's perspective, care delivery, and financial levers (or lack of) are some of the categories that the interview questions looked into. Therefore, the data gathered would be used to guide and refine the concept of CHoF.

Project description:In vitro embryo culture often falls short of mimicking the physiological dynamism occurring in the reproductive tract, prompting developmental plasticity in mammalian embryos with consequential genotypic and phenotypic deviations. Recent research highlights the potential of biological derivatives in in vitro culture to mitigate these effects, being the extracellular matrix (ECM) one of the most important components in retaining structural and biological signals derived from the native source tissue. Current bioengineering techniques could provide ECM-based biomaterials mimicking the native environment and offering optimal embryonic development. Rabbit oviducts (n = 24) were decellularized and solubilized to create tissue-specific ECM (OviECM) hydrogels. Following physicochemical characterization, these hydrogels were applied as coatings for the in vitro culture of two-cell embryos over 48 h, along with embryos cultured under In vitro control conditions (n = 218/group), which were subsequently transferred to recipient females. A subset of embryos was recovered on day 6 for transcriptomic analysis (n = 75-80/group), while the remaining embryos were used to assess implantation and birth rates. Rabbit weights were monitored over 20 weeks post-delivery, with blood tests conducted at weeks 8 and 20. Bayesian inference methods were used for statistical analysis. Differences were considered relevant if P ≥ 0.8 (80%). No differences in embryo development and morphology were detected between the OviECM coating and In vitro control conditions. However, embryos cultured on these coatings exhibited upregulation of pathways involved in antigen presentation and immune system activation, as well as, increased cellular response to external stimulus and intracellular protein transport. The implantation and live birth rates were significantly higher in the coating group than in the In vitro control group (30.8% vs. 26.1% and 21.2% vs. 18.1%, respectively). During the first 20 weeks of life, the animals from the coating group showed higher weights than the In vitro control group P0 > 0.8. The animals of both experimental groups showed normal blood parameters. Implementation of OviECM coatings allows for improving in vitro conditions and decreases postnatal phenotypic deviations after assisted reproductive technology (ART). This study could initiate a new embryo culture techniques era to guarantee that ART is utilized in the most efficient and safest possible practice.

Dataset Information

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

Publications

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

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