Microencapsulation of cells
Encapsulation can serve a multitude of purposes from improving cell cultivation in vitro to providing a physical barrier during transplantation in vivo. Cell culture is enhanced as core-shell microcapsules allow for the cells to aggregate into 3D spheroids, improving cellular communication and mimicking native architecture. Microencapsulated cells also can be cultured at a higher density since the capsule protects the cells from excessive sheer forces that are necessary to enhance nutrient and oxygen diffusion. Transplantation of cellular therapy also is improved with encapsulation as the physical barrier prevents immune destruction and avoids the need for immunosuppressive medications and their sequelae.
Our team has been employing microfluidics to fabricate cell-carrying hydrogel microcapsules of uniform diameter and cell number. We have demonstrated that both stem cells and adult cells may be encapsulated and maintained within these hydrogel carriers over long periods of time without losing viability or function.
Incorporating heparin, an extracellular matrix component, into the shell of these hydrogel microcapsules also serves as a reservoir for growth factors that have heparin-binding domains. Subsequently, heparin-containing capsules demonstrate improved cell viability and function while reducing growth factor requirements.
Experiments are underway to differentiate pluripotent stem cells into hepatocytes inside microcapsules.
Microencapsulation of cells using a droplet microfluidic device
The left panel shows the microfluidic encapsulation system developed by our team that allows us to entrap single cells in core-shell droplets that are later cross-linked to become hydrogel microcapsules. The right panel shows that encapsulation conditions have been optimized to ensure high cell viability and high efficiency of cell loading into microcapsules. Because microcapsules contain a hydrogel shell and aqueous core, entrapped single cells rapidly aggregate to form spheroids.
Key publications
Gwon K, Choi D, de Hoyos-Vega JM, Baskaran H, Gonzalez-Suarez AM, Lee S, Hong HJ, Nguyen KM, Dharmesh E, Sugahara G, Ishida Y, Saito T, Stybayeva G, Revzin A. Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor. Bioactive Materials. 2023.
Gwon K, Hong HJ, Gonzalez-Suarez AM, Slama MQ, Choi D, Hong J, Baskaran H, Stybayeva G, Peterson QP, Revzin A. Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors. Bioactive Materials. 2022.
Siltanen C, Diakatou M, Lowen J, Haque A, Rahimian A, Stybayeva G, Revzin A. One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids. Acta Biomaterialia. 2017.
Siltanen C, Yaghoobi M, Haque A, You J, Lowen J, Soleimani M, Revzin A. Microfluidic fabrication of bioactive microgels for rapid formation and enhanced differentiation of stem cell spheroids. Acta Biomaterialia. 2016.