Biomolecular strategies for cell surface engineering

Cell encapsulation;Islet transplantation;Cell surface engineering;Layer-by-layer self assembly;Thrombomodulin;Conformal coating

Wilson, John Tanner ; Biomedical Engineering

University:Georgia Institute of Technology

Department:Biomedical Engineering

关键词: Cell encapsulation;    Islet transplantation;    Cell surface engineering;    Layer-by-layer self assembly;    Thrombomodulin;    Conformal coating;   

Others  :  https://smartech.gatech.edu/bitstream/1853/33846/1/wilson_john_t_200905_phd.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

Islet transplantation has emerged as a promising cell-based therapy for the treatment of diabetes, but its clinical efficacy remains limited by deleterious host responses that underlie islet destruction.In this dissertation, we describe the assembly of cell surface-supported thin films that confer molecular-level control over the composition and biophysicochemical properties of the islet surface with implications for improving islet engraftment. Specifically, the process of layer-by-layer (LbL) polymer self assembly was employed to generate nanothin films of diverse architecture with tunable properties directly on the extracellular surface of individual islets.Importantly, these studies are the first to report in vivo survival and function of nanoencapsulated cells, and have helped establish a conceptual framework for translating the diverse applications of LbL films to cellular interfaces. Additionally, through proper design of film constituents, coatings displaying ligands and bioorthogonally reactive handles may be generated, providing a modular strategy for incorporating exogenously derived regulators of host responses alongside native constituents of the islet surface.Towards this end, a strategy was developed to tether thrombomodulin to the islet surface in a site-specific manner, thereby facilitating local generation of the powerful anti-inflammatory agent, activated protein C.Collectively, this work offers novel biomolecular strategies for cell surface engineering with broad biomedical and biotechnological applications in cell-based therapeutics and beyond.