Next Generation Biomaterials Discovery for Regenerative Medicine

Human pluripotent stem cells (hPSCs) have the capability to provide a limitless source of physiologically relevant human tissue for drug screening and therapeutic applications. Differentiated cell types can possess an immature phenotype limiting their scope of use, with hPSC-derived cardiomyocytes a...

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Main Author: Thorpe, Jordan
Format: Thesis (University of Nottingham only)
Language:English
English
Published: 2020
Online Access:https://eprints.nottingham.ac.uk/60661/
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author Thorpe, Jordan
author_facet Thorpe, Jordan
author_sort Thorpe, Jordan
building Nottingham Research Data Repository
collection Online Access
description Human pluripotent stem cells (hPSCs) have the capability to provide a limitless source of physiologically relevant human tissue for drug screening and therapeutic applications. Differentiated cell types can possess an immature phenotype limiting their scope of use, with hPSC-derived cardiomyocytes a prominent example. To truly realise the potential of hPSCs, fully defined and xeno-free culture systems must be in place, that are economically viable for industrial scale application. Additionally, the system must be capable of inducing relevant maturation of states of cell types cultured. In this thesis a readily available and economical polymer library primarily composed of 281 acrylates & acrylamides were screened using polymer microarray technology, totalling 37,103 cell-surface interactions. Serially passaged hPSCs were examined by RT-qPCR, flow cytometry, immunostaining, trilineage differentiation, integrin blocking, and phosphokinase protein arrays. hPSCs maintained trilineage differentiation capability, with inter-cell line differences discovered for expression of SOX2, SOX1, PAX6, and the phosphorylated state of protein kinases – compared to a Matrigel control. Polymers that supported ≥7-day hPSC-CM attachment underwent studies into the contraction and electrophysiology properties of hPSC-CMs on primary amine polymeric surfaces compared to the Matrigel. Minor changes to the maturation state were observed, with further examination required for a definitive conclusion.
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format Thesis (University of Nottingham only)
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English
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spelling nottingham-606612025-02-28T14:55:32Z https://eprints.nottingham.ac.uk/60661/ Next Generation Biomaterials Discovery for Regenerative Medicine Thorpe, Jordan Human pluripotent stem cells (hPSCs) have the capability to provide a limitless source of physiologically relevant human tissue for drug screening and therapeutic applications. Differentiated cell types can possess an immature phenotype limiting their scope of use, with hPSC-derived cardiomyocytes a prominent example. To truly realise the potential of hPSCs, fully defined and xeno-free culture systems must be in place, that are economically viable for industrial scale application. Additionally, the system must be capable of inducing relevant maturation of states of cell types cultured. In this thesis a readily available and economical polymer library primarily composed of 281 acrylates & acrylamides were screened using polymer microarray technology, totalling 37,103 cell-surface interactions. Serially passaged hPSCs were examined by RT-qPCR, flow cytometry, immunostaining, trilineage differentiation, integrin blocking, and phosphokinase protein arrays. hPSCs maintained trilineage differentiation capability, with inter-cell line differences discovered for expression of SOX2, SOX1, PAX6, and the phosphorylated state of protein kinases – compared to a Matrigel control. Polymers that supported ≥7-day hPSC-CM attachment underwent studies into the contraction and electrophysiology properties of hPSC-CMs on primary amine polymeric surfaces compared to the Matrigel. Minor changes to the maturation state were observed, with further examination required for a definitive conclusion. 2020-07-24 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/60661/1/Jordan%20Thorpe%20Thesis%20Final%20Submission.pdf application/pdf en arr https://eprints.nottingham.ac.uk/60661/2/Jordan%20Thorpe%20Thesis%20Redacted%20Submission.pdf Thorpe, Jordan (2020) Next Generation Biomaterials Discovery for Regenerative Medicine. PhD thesis, University of Nottingham.
spellingShingle Thorpe, Jordan
Next Generation Biomaterials Discovery for Regenerative Medicine
title Next Generation Biomaterials Discovery for Regenerative Medicine
title_full Next Generation Biomaterials Discovery for Regenerative Medicine
title_fullStr Next Generation Biomaterials Discovery for Regenerative Medicine
title_full_unstemmed Next Generation Biomaterials Discovery for Regenerative Medicine
title_short Next Generation Biomaterials Discovery for Regenerative Medicine
title_sort next generation biomaterials discovery for regenerative medicine
url https://eprints.nottingham.ac.uk/60661/