(335g) A Computational and Experimental Design of Toroidal-Spiral Particles As a Cell Macro-Encapsulation System

Cell encapsulation systems for treatment of chronic diseases like type I diabetes serves as an effective mechanism to deliver therapeutic solution from hormone producing cells, such as beta cells or islets of Langerhans. Ideal therapeutic approaches involving transplantation of Islets of Langerhans requires encapsulation with optimal immunoprotection, nutrient and oxygen transport, excellent robustness and retrievability. We aim to design a system based on polymeric self-assembled Toroidal-Spiral Particles (TSP), which feature large encapsulation capacity and ensure large surface area to volume ratio for effective molecular diffusion of nutrients/oxygen.

Formation of TSP is through a self-assembly process that starts with sedimentation and intricate deformation of a polymeric drop in a bulk solution, and ends with solidification by photo-initiated cross-linking of the polymeric matrix.^1,2 In our previously developed fluid-dynamic technology, the generation and dimensions of the toroidal channels are controlled by We, Re and drop/bulk viscosity ratio during drop surface impact and sedimentation. These TSPs have served as a delivery system for proteins and small molecules allowing for dual drug encapsulation with independent release pathways, whose release kinetics can be tailored by the toroidal channel length and width.³

We have further investigated the formation of TSPs with fine-controlled channel morphology and dimensions, exploring different fluid dynamic operating conditions. Of particular interest are the TS channels formed at low Reynolds number and small viscosity ratios. In this work, TSP formation can be described into two stages, (i) drop infusion (below the surface of the bulk), (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 initial conditions for final TS channel structure. Using our creeping-flow numerical simulations of single-drop sedimentation, which closely resemble the experimental shapes, we could monitor and tailor the internal structure of the TSP. These simulations accurately track complex drop configurations initiated from injections at different Re, evaluating additionally the effect of several drop/bulk viscosity ratios. The development of a flow map and understanding the fundamental hydrodynamics interactions will ultimately aid in the design of TSPs with tunable empty channel towards drug delivery and cell encapsulation.

1. Sharma, V., Szymusiak, M., Shen, H., Nitsche, L. C. & Liu, Y. Formation of Polymeric Toroidal-Spiral Particles. Langmuir 28, 729–735 (2012).
2. Szymusiak, M., Sharma, V., Nitsche, L. C. & Liu, Y. Interaction of sedimenting drops in a miscible solution – formation of heterogeneous toroidal-spiral particles. Soft Matter 8, 7556–7559 (2012).
3. Sharma, V. et al. Toroidal-Spiral Particles for Codelivery of Anti-VEGFR-2 Antibody and Irinotecan: A Potential Implant to Hinder Recurrence of Glioblastoma Multiforme. Biomacromolecules 15, 756–762 (2014).
4. Leon Plata, P., Liu, Y. and Nitsche, L. C., Interaction of multiple drops and formation of toroidal-spiral particles, Phys. Rev. Fluids, 3, no. 9 (2018): 093601.