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Multiscale Biomaterials for Cell and Tissue Engineering
Başlık:
Multiscale Biomaterials for Cell and Tissue Engineering
Yazar:
Agarwal, Pranay, author.
ISBN:
9780438091641
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (182 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Xiaoming He Committee members: Gunjan Agarwal; Keith Gooch; Yi Zhao.
Özet:
The aim of tissue engineering is to fabricate functional tissue constructs for treating diseases. Contemporary approach for tissue engineering is to embed cells in homogenous three-dimensional (3D) macroscopic scaffolds for mimicking the function of extracellular matrix (ECM) in tissues. However, the native ECM is usually not homogenous and these macroscopic scaffolds are suboptimal due to the limited diffusion length of oxygen and nutrients in cellularized tissues. In this dissertation work, cell microencapsulation and microfluidic technologies are utilized to fabricate multiscale heterogeneous biomaterials for resolving these issues.
First, the development of a novel non-planar microfluidic flow-focusing device for high-throughput encapsulation of mouse embryonic stem cells (mESCs) in a liquid core of microcapsules with an alginate hydrogel shell is reported. Using the non-planar microfluidic device, mESCs can be encapsulated in the core with high viability to form uniform sized aggregates, to mimic the growth of totipotent-pluripotent stem cells in early pre-hatching embryos. Further, it is shown that mESCs cultured in the biomimetic microcapsules have higher pluripotency and differentiation potential than the cells cultured under traditional two-dimensional (2D) condition. Utilizing the same microfluidic device, biomimetic ovarian microtissue consisting of an ovarian follicle embedded in microcapsules with a collagen core and alginate hydrogel shell is fabricated. This miniaturized 3D culture of early secondary preantral follicles facilitate their development to the antral stage. The study revealed the crucial role of mechanical heterogeneity in the mammalian ovary in regulating follicle development and ovulation. It is also demonstrated that the proliferation, differentiation, and development of mESCs and preantral follicles can be modulated by changing the composition of ECM in the core of the microcapsules.
Next, a bottom-up approach for fabricating 3D vascularized human breast tumor model with the core-shell microencapsulation technology is developed. Microtumors (i.e., 3D aggregates of cancer cells) are generated in core-shell microcapsules and used together with human endothelial cells and human adipose derived stem cells (hADSCs) as building blocks to self-assemble into vascularized tumor in collagen hydrogel. The utility of the platform in drug screening is further demonstrated. It is shown that vascularization can render increased cancer resistance to chemotherapy. This vascularized tumor system may be valuable for in vitro drug screening to better predict the drug efficacy in cancer patients. Lastly, a multiscale system for efficient co-delivery of cells and proteins/growth factors in vivo is developed to address the issue of low cell survival associated with cell delivery in vivo. The multiscale delivery system is comprised of therapeutic agents-laden nanoparticles encapsulated in microcapsules (nano-in-micro), hADSCs, and collagen hydrogel. The nano-in-micro system enables sustained release of therapeutic proteins to interact with their receptors on the hADSCs in the system which significantly improves the survival and proliferation of the hADSCs after implantation. This is shown to greatly facilitate the tissue regeneration in an ischemic disease model.
To conclude, this dissertation work demonstrates how microscale encapsulation of cells via microfluidics provides a powerful suite of tools to engineering the cellular microenvironment at micro and macro scales. The technologies and systems described here could potentially help in building tissue engineering constructs that enable treatment of a myriad of human diseases.
Notlar:
School code: 0168
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687031.1) | 687031-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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