DEVELOPMENT OF A 3D ZWITTERIONIC HYDROGEL SYSTEM FOR CELL CULTURE AND EXTRACELLULAR VESICLES
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Since the release of Extracellular vesicles (EVs) has been recognized as a common method of intercellular communication between cells, they are essential in various biological processes and possess significant therapeutic potential. Maintaining high-quality control of donor cell cultures and EVs is critical for effective loading and delivery.[1] However, current methods for EV production face substantial limitations. Consequently, enhancing the production of natural EVs through the development and utilization of high-capacity "cell factories" is a promising strategy to achieve a substantial quantity of EVs, ensuring their integrity, preserving their biological activity, and maintaining reproducibility. Although previous research has shown the effectiveness of 3D zwitterionic scaffolds in supporting the growth of suspension hematopoietic stem and progenitor cells, the application of hydrogels for 3D culturing of EV-producing cells like human embryonic kidney (HEK) cells and neutrophils has not been extensively explored due to challenges such as limited hydrolytic stability, inadequate functionality, and inefficient synthesis processes.[2] In this study, we introduce an efficient method for synthesizing functional poly(carboxybetaine) (PCB) and TMAO-derived zwitterionic polymers (PTMAO), providing access to star-shaped zwitterionic polymers with excellent hydrolytic stability, superior functionality, and adjustable stiffness under physiological conditions.[3] The newly developed zwitterionic hydrogel system facilitates the direct encapsulation of cells and the release of EVs in a user-friendly manner. The 3D culture of HEK cells using the hydrogel shows EVs production with high yield, underscoring the potential of this innovative zwitterionic hydrogel system for scalable EVs production.