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Regenerating dynamic organs using biomimetic patches.

ABSTRACT: The regeneration of dynamic organs remains challenging because they are intrinsically anisotropic and undergo large volumetric deformation during normal or pathological function. This hampers the durability and applicability of regenerative medicine approaches. To address the challenges of organ dynamics, a new class of patches have emerged with anisotropic and auxetic properties that mimic native tissue biomechanics and accommodate volumetric deformation. Here, we outline the critical design, materials, and processing considerations for achieving optimal patch biomechanics according to target pathology and summarize recent advances in biomimetic patches for dynamic organ regeneration. Furthermore, we discuss the challenges and opportunities which, if overcome, would open up new applications in organ regeneration and expedite the clinical translation of patch-based therapeutics.

SUBMITTER: Chansoria P

PROVIDER: S-EPMC8831394 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Regenerating dynamic organs using biomimetic patches.

Chansoria Parth P Etter Emma L EL Nguyen Juliane J

Trends in biotechnology 20210816 3

The regeneration of dynamic organs remains challenging because they are intrinsically anisotropic and undergo large volumetric deformation during normal or pathological function. This hampers the durability and applicability of regenerative medicine approaches. To address the challenges of organ dynamics, a new class of patches have emerged with anisotropic and auxetic properties that mimic native tissue biomechanics and accommodate volumetric deformation. Here, we outline the critical design, m ...[more]

PMID: 34412924

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Project description:Background & aimsThe adult liver is the main detoxification organ and routinely is exposed to environmental insults but retains the ability to restore its mass and function upon tissue damage. However, extensive injury can lead to liver failure, and chronic injury causes fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, the transcriptional regulation of organ repair in the adult liver is incompletely understood.MethodsWe isolated nuclei from quiescent as well as repopulating hepatocytes in a mouse model of hereditary tyrosinemia, which recapitulates the injury and repopulation seen in toxic liver injury in human beings. We then performed the assay for transposase accessible chromatin with high-throughput sequencing specifically in repopulating hepatocytes to identify differentially accessible chromatin regions and nucleosome positioning. In addition, we used motif analysis to predict differential transcription factor occupancy and validated the in silico results with chromatin immunoprecipitation followed by sequencing for hepatocyte nuclear factor 4α (HNF4α) and CCCTC-binding factor (CTCF).ResultsChromatin accessibility in repopulating hepatocytes was increased in the regulatory regions of genes promoting proliferation and decreased in the regulatory regions of genes involved in metabolism. The epigenetic changes at promoters and liver enhancers correspond with the regulation of gene expression, with enhancers of many liver function genes showing a less accessible state during the regenerative process. Moreover, increased CTCF occupancy at promoters and decreased HNF4α binding at enhancers implicate these factors as key drivers of the transcriptomic changes in replicating hepatocytes that enable liver repopulation.ConclusionsOur analysis of hepatocyte-specific epigenomic changes during liver repopulation identified CTCF and HNF4α as key regulators of hepatocyte proliferation and regulation of metabolic programs. Thus, liver repopulation in the setting of toxic injury makes use of both general transcription factors (CTCF) for promoter activation, and reduced binding by a hepatocyte-enriched factor (HNF4α) to temporarily limit enhancer activity. All sequencing data in this study were deposited to the Gene Expression Omnibus database and can be downloaded with accession number GSE109466.

Dataset Information

Regenerating dynamic organs using biomimetic patches.

Publications

Regenerating dynamic organs using biomimetic patches.

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