Microfabrication of Asymmetric, Homogeneous Cell-laden Hydrogel Microcapsules
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Microfabrication of asymmetric, homogeneous cell-laden hydrogel microcapsules Tram T. Dang1+, Qiaobing Xu1+, Kaitlin M. Bratlie1,3, Esther S. O’Sullivan4, Xiao Y. Chen1, Robert Langer1,2 and Daniel G. Anderson2 + These authors contributed equally to the work.
(1) Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, (2) David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , 77 Massachusetts Ave, Cambridge, MA 02139, (3) Department of Anesthesiology, Children Hospital Boston, 300 Longwood Ave, Boston, MA 02115,(4) Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215 ABSTRACT Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the mesh material/surface properties associated with efficient encapsulation were identified. Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucoseresponsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process. INTRODUCTION Cell encapsulation allows for the transplantation of non-autologous cells without the use of immunosuppressive drugs, which have potentially severe side-effects 1. Transplanted living cells are protected from the host immune system because they are encapsulated in a semipermeable hydrogel membrane which allows the diffusion of nutrients and cellular metabolic products while excluding antibodies and immune cells 2. Islets or other insulin-secreting cells are commonly encapsulated by electrostatic droplet generation for transplantation into diabetic hosts3. The electrostatic droplet generator system is appropriate for the continuous production of hydrogel microcapsules from a polymer/cell mixture of an unchanged composition4. However, this apparatus, which requires sterilization of the bioreactor chamber after each use, is not convenient for studies which involve screening a large number of different material formulations5 . Polydimethylsiloxane (PDMS) molds produced via soft-lithography have also been explored as an alternative approach to fabricate hydrogel microcapsules in 2D arrays as well as discrete modules 6-9. However, a potential challenge for this technique is the difficulty of releasing the microcapsules from the PDMS mold without damaging the cells 6-9. Furthermore, this method is still limited by the necessity of a microfabrication process to generate the PDMS membranes and the difficul
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