Abstract
Mechanical signals such as fluid flow shear stresses are strong regulators for directing the organization of vascular networks. Comprehending the coordination between vascular structure and flow dynamics within complex tissue architecture is crucial. With this understanding, one could adjust the organization within engineered tissues by manipulating the tissue microenvironment and associated flows. However, it is challenging due to the limitations in the pre-clinical models and the optical inaccessibility and aseptic nature of these models. Creating efficient engineering tools to manipulate both in vivo and in vitro vascular organization using mechanical signals is the goal. This thesis describes three main strategies (i) to probe (ii) to perturb and (iii) to predict the vascular organization using multidisciplinary approaches.
Firstly, a transparent ex ovo chicken chorioallantoic membrane (CAM) engineered platforms were developed and multimodal imaging techniques such as laser speckle contrast imaging (LSCI) and side-stream dark field (SDF) microscopy systems were applied to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocyte movements within individual blood vessels of developing chick embryo. Additionally, using biofabricated vascularized tissue model, the application of LSCI and SDF were demonstrated to study flow perfusion effects in a non-invasive fashion. Secondly, novel perturbations tools were developed to study the multivariable organizational parameters, using external shapes and flows. This provides us with valuable information that can be translated to an in vitro tissue engineering setting. Finally, hybrid computational models were developed to predict the microvasculature evolution and their responses to external mechanical and chemical signals.
Together, this thesis introduces several innovative approaches and multidisciplinary concepts that facilitate the development and tuning of vascular organization within both native and engineered tissues.
Firstly, a transparent ex ovo chicken chorioallantoic membrane (CAM) engineered platforms were developed and multimodal imaging techniques such as laser speckle contrast imaging (LSCI) and side-stream dark field (SDF) microscopy systems were applied to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocyte movements within individual blood vessels of developing chick embryo. Additionally, using biofabricated vascularized tissue model, the application of LSCI and SDF were demonstrated to study flow perfusion effects in a non-invasive fashion. Secondly, novel perturbations tools were developed to study the multivariable organizational parameters, using external shapes and flows. This provides us with valuable information that can be translated to an in vitro tissue engineering setting. Finally, hybrid computational models were developed to predict the microvasculature evolution and their responses to external mechanical and chemical signals.
Together, this thesis introduces several innovative approaches and multidisciplinary concepts that facilitate the development and tuning of vascular organization within both native and engineered tissues.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 14 Jan 2025 |
Place of Publication | Enschede |
Publisher | |
Print ISBNs | 978-90-3665-6425-0 |
Electronic ISBNs | 978-90-365-6426-7 |
DOIs | |
Publication status | Published - Jan 2025 |