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High-Throughput Production of Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor

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Abstract

Microencapsulation of human mesenchymal stromal cells (MSCs) via electrospraying has been well documented in tissue engineering and regenerative medicine. Herein, we report the use of microencapsulation, via electro-spraying, for MSC expansion using a commercially available hydrogel that is durable, optimized to MSC culture, and enzymatically degradable for cell recovery. Critical parameters of the electrospraying encapsulation process such as seeding density, correlation of microcapsule output with hydrogel volume, and applied voltage were characterized to consistently fabricate cell-laden microcapsules of uniform size. Upon encapsulation, we then verified ∼10× expansion of encapsulated MSCs within a vertical-wheel bioreactor and the preservation of critical quality attributes such as immunophenotype and multipotency after expansion and cell recovery. Finally, we highlight the genetic manipulation of encapsulated MSCs as an example of incorporating bioactive agents in the capsule material to create new compositions of MSCs with altered phenotypes.

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Acknowledgements

This research was conducted with support by under Contract number T0067 from the Advanced Regenerative Medicine Institute, BioFAB USA and Grant Nos. R01EB012521 (BP) and R01EB02872 (BP) awarded by the National Institutes of Health.

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Conceptualization: BP, MT. Execution of Experiments: MT, PJ, RB. Formal Analysis: MT, PJ, RB. Manuscript Preparation: MT, PJ, RB. Funding Acquisition: BP.

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Correspondence to Biju Parekkadan.

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Single donor bone marrow was donated for purchase from Lonza (Walkersville, MD, USA). Lonza obtained permission for its use in research applications by written informed consent.

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Teryek, M., Jadhav, P., Bento, R. et al. High-Throughput Production of Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor. Biotechnol Bioproc E 28, 528–544 (2023). https://doi.org/10.1007/s12257-023-0020-9

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