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Pedroza, Rene G.

University of British Columbia

Encapsulated beta cell replacement therapies can restore blood glucose control and reduce the need for immunosuppression, and thus should become an attractive alternative for millions of people who currently treat their diabetes with insulin. This work describes two approaches to immobilize pancreatic cells in alginate using: (i) microencapsulation by emulsification and internal gelation in stirred vessels, and (ii) macroencapsulation in fibres by co-axial flow-focusing bioprinting. Scalable generation of microspheres sized 300-800 µm from 5% alginate solutions and higher cell encapsulation yields were attained using grid impellers and by reducing alginate viscosity through thermal treatments. The encapsulation yield was 2-fold higher for 11-µm cells compared to 110-µm aggregates. Also, large numbers of empty microspheres were observed after aggregate encapsulation, likely due to their stochastic distribution in the alginate beads. Microspheres containing aggregates were separated by sedimentation in a continuous density gradient that removed ~50% of the empty bead volume, followed by centrifugation to remove unencapsulated cells. Separation based on density differences could be adapted for other cell microencapsulation technologies by tuning the continuous density gradient as a function of volume fraction per bead. The last part of this thesis, using an analytical mass transfer model, describes the design of cell-laden multi-layered fibres based on avoiding oxygen limitations. Radial displacement of the cell-containing layer, obtained by constraining it between two acellular alginate layers to form an annulus, can increase cell loading per unit length of fibre without compromising cell oxygenation and insulin secretory capacity. This novel bioprinted fibre geometry could be used to encapsulate insulin-producing cells in retrievable devices and leverage oxygenation via passive diffusion as an option to develop carefree alternatives for reversal of diabetes.

Text

2023-03-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/81087

Biomedical Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/