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Design and Fabrication of Toroidal Spiral Particles for Multi-compound Delivery and Cell Encapsulation
thesisposted on 01.05.2021, 00:00 by Paola Andrea Leon Plata
Cell encapsulation and drug delivery systems serve as an effective mechanism to deliver therapeutic solution from drugs and cells. Fabrication of encapsulating technologies for multiple compounds or specific cells type, size and metabolic requirements might be challenging. We optimize our previously developed fluid-dynamic technology based one single drop self-assembly process to produce solid toroidal-spiral (TS) particles. These particles served as a delivery system whose payload release kinetic is tailored by the toroidal channel length and width. In this thesis, we explore further the design of a system capable of tuning the encapsulation capacity for a single compound or cells and multiple compounds within on delivery system, TSPs. Furthermore, these TSPs are designed to ensure large surface area to volume ratio for effective molecular diffusion in/out of the encapsulated mass. Throughout this study we investigated the formation of TSPs with fine-controlled channel morphology and dimensions, studying different fluid dynamic operating conditions. Of particular interest are the toroid-channels formed at low Reynold number and small drop/bulk viscosity ratios. In this work, TSP formation can be described into two stages, (i) drop infusion (below surface), (ii) subsequent sedimentation and entrainment of bulk solution. Initial infusion rate, Re and viscosity ratio affect the initial drop shape and tail length, which are crucial on final TS channel structure. We characterized the dimensions of the particles formed at various fluid dynamic conditions. Low Re number and viscosity ratio (>1) of the polymer drop to the bulk solution are desirable to obtain T-S particles of reasonable size and sufficient loading capacity, which are of particular interest for cell encapsulation and drug delivery. We demonstrate the feasibility to fabricate these particles at various PEGDA compositions and the encapsulation of human islets of Langerhans towards the treatment of type 1 diabetes. Encapsulated islets showed excellent in vitro viability and cell functionality. Preliminary biocompatibility of the TSPs on C57BL/6 mice shows minimal inflammatory response after intraperitoneal space transplantation. Furthermore, using creeping-flow numerical simulations of a single drop and multiple drop sedimentation, we could monitor and tailor single particles internal structure and effective entrapment of multiple drops into a single TSP.