Publication
Mechanosensing microcapsules to direct stem cell differentiation for tissue regeneration applications
| Summary: | The ultimate goal of tissue engineering and regenerative medicine (TERM) is to unlock the therapeutic potential of stem cells, precisely directing their fate towards desired functions to develop biomimetic tissues in vitro, requiring novel approaches to recapitulate the functionality and architectural features of native tissues. In natural tissues, cells are arranged into functional units or building blocks collaborating to regulate development and maintain normal body functions. Cells within their microenvironment are controlled by various mechanical and biochemical signals received from their niche which dictate their stemness, multipotency, and ultimately regulate their differentiation phenotype. A better understanding of these environmental factors enables improved control over cell fate for biomedical purposes. Moreover, bottom-up approaches facilitate the development of modular biomimetic constructs mimicking the complexity, heterogeneity, and biological functions of native tissues. Therefore, this PhD proposal aimed to design new strategies to recapitulate key functional features of the native environment. To achieve this, liquefied microcapsules were developed as mechanosensing platforms to explore the regulation of stem cell fate by engineering their microenvironment with customized stimulation features. The effects of two important mechanical cues, shear stress and hydrostatic pressure, were investigated on adipose derived mesenchymal stem cells (MSC) cultured within microcapsules as building blocks. To further enhance the functionality of the developed biomimetic tissues, we introduced a new approach for creating heterogeneous microenvironments with decoupled microand macroenvironments within a single three dimensional construct, achieved by incorporating liquefied-based compartments into hydrogel systems. Ultimately, liquefied microcapsules were employed for development of a hybrid bioink composed of building blocks customized with a biological cue to guide the encapsulated cells. Taken together, our studies highlight the significance of mechanical cues for TERM applications and illustrate how to achieve functional biomimetic architectures by assembling living functional units with tailored stimulation properties. |
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| Main Authors: | Hasankolaei, Maryam Ghasemzadeh |
| Subject: | Mechanical cues Osteogenic differentiation Heterogeneous microenvironments Modular assembly Bioprinting |
| Year: | 2024 |
| Country: | Portugal |
| Document type: | doctoral thesis |
| Access type: | embargoed access |
| Associated institution: | Universidade de Aveiro |
| Language: | English |
| Origin: | RIA - Repositório Institucional da Universidade de Aveiro |
| Summary: | The ultimate goal of tissue engineering and regenerative medicine (TERM) is to unlock the therapeutic potential of stem cells, precisely directing their fate towards desired functions to develop biomimetic tissues in vitro, requiring novel approaches to recapitulate the functionality and architectural features of native tissues. In natural tissues, cells are arranged into functional units or building blocks collaborating to regulate development and maintain normal body functions. Cells within their microenvironment are controlled by various mechanical and biochemical signals received from their niche which dictate their stemness, multipotency, and ultimately regulate their differentiation phenotype. A better understanding of these environmental factors enables improved control over cell fate for biomedical purposes. Moreover, bottom-up approaches facilitate the development of modular biomimetic constructs mimicking the complexity, heterogeneity, and biological functions of native tissues. Therefore, this PhD proposal aimed to design new strategies to recapitulate key functional features of the native environment. To achieve this, liquefied microcapsules were developed as mechanosensing platforms to explore the regulation of stem cell fate by engineering their microenvironment with customized stimulation features. The effects of two important mechanical cues, shear stress and hydrostatic pressure, were investigated on adipose derived mesenchymal stem cells (MSC) cultured within microcapsules as building blocks. To further enhance the functionality of the developed biomimetic tissues, we introduced a new approach for creating heterogeneous microenvironments with decoupled microand macroenvironments within a single three dimensional construct, achieved by incorporating liquefied-based compartments into hydrogel systems. Ultimately, liquefied microcapsules were employed for development of a hybrid bioink composed of building blocks customized with a biological cue to guide the encapsulated cells. Taken together, our studies highlight the significance of mechanical cues for TERM applications and illustrate how to achieve functional biomimetic architectures by assembling living functional units with tailored stimulation properties. |
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Funded activities
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