Scaglioni, Dominic;
(2024)
Utilising Instructive Hydrogels to Model Embryonic Heart and Organ Development in vitro.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
During development, the heart transforms from a linear tube to a multichambered organ. This process requires orchestration of both mechanical and chemical cues between primordial cardiac tissues and the surrounding environment. However, there remains a significant disparity between the amount of available human data and data acquired from animal studies. To date, existing in vitro models are unable to replicate the defined cellular features and microarchitectural structures of the early embryonic heart. By using a recently developed bioprinting technology that enables the photo-crosslinking of biopolymers within hydrogels, we created a novel 3D tissue-engineered in vitro model of the linear heart tube. We were able to finely tune the stiffness of the hydrogel over biologically matched ranges by modulating the bioprinting parameters. This enabled patterning of mechanical properties with micrometric resolution allowing us to investigate the impact of hydrogel biomechanics on cell phenotype. Our bioprinted hydrogel scaffolds enabled robust differentiation of human induced pluripotent stem cell derived cardiomyocytes (hiPSCs-CMs) with the formation of a single cell layer around the hydrogel scaffold with correct polarisation, coupled with representative morphology and geometry to the linear heart tube in vivo. The mechanical properties of the hydrogel scaffolds were designed to be compliant with hiPSC-CM contraction with corresponding changes in the luminal cross-section depending on scaffold stiffness. The inclusion of multilamellar lipid nanoparticles within these bio-printable hydrogel structures also enabled the regional patterning of hiPSC-CMs to generate discrete ventricular-like and atrial-like lineages by modulating retinoic acid signalling. Ultimately, this in vitro model of early-stage human heart development lays the foundation to explore the mechanisms that drive human cardiogenesis and presents a novel method for in vitro cell patterning to mimic in vivo developmental processes in vitro.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Utilising Instructive Hydrogels to Model Embryonic Heart and Organ Development in vitro |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10192941 |
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