Book Description

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.