Multifunctional Thermoresponsive Microcarriers for High‐Throughput Cell Culture and Enzyme‐Free Cell Harvesting

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2021-11, Vol.17 (44), p.e2103192-n/a
• Main Authors: Dabiri, Seyed Mohammad Hossein, Samiei, Ehsan, Shojaei, Shahla, Karperien, Lucas, Khun Jush, Bardia, Walsh, Tavia, Jahanshahi, Maryam, Hassanpour, Sadegh, Hamdi, David, Seyfoori, Amir, Ahadian, Samad, Khademhosseini, Ali, Akbari, Mohsen
• Format: Article
• Language: English
• Subjects: Cell Adhesion; Cell Culture Techniques; Cell Proliferation; Composition; Controlled release; Enzymes; enzyme‐free cell harvesting; Gelatin; gelatin methacryloyl; Growth factors; Humans; Hydrogels; interpenetrating hydrogel microcarriers; Mechanical properties; Methacrylates; Microfluidics; Nanotechnology; Polydispersity; Polyethylene glycol; Polyisopropyl acrylamide; Room temperature; Size distribution; Stiffness; temperature‐responsive microcarriers
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202103192

An effective treatment of human diseases using regenerative medicine and cell therapy approaches requires a large number of cells. Cultivation of cells on microcarriers is a promising approach due to the high surface‐to‐volume ratios that these microcarriers offer. Here, multifunctional temperature‐responsive microcarriers (cytoGel) made of an interpenetrating hydrogel network composed of poly(N‐isopropylacrylamide) (PNIPAM), poly(ethylene glycol) diacrylate (PEGDA), and gelatin methacryloyl (GelMA) are developed. A flow‐focusing microfluidic chip is used to produce microcarriers with diameters in the range of 100–300 μm and uniform size distribution (polydispersity index of ≈0.08). The mechanical properties and cells adhesion properties of cytoGel are adjusted by changing the composition hydrogel composition. Notably, GelMA regulates the temperature response and enhances microcarrier stiffness. Human‐derived glioma cells (U87) are grown on cytoGel in static and dynamic culture conditions with cell viabilities greater than 90%. Enzyme‐free cell detachment is achieved at room temperature with up to 70% detachment efficiency. Controlled release of bioactive molecules from cytoGel is accomplished for over a week to showcase the potential use of microcarriers for localized delivery of growth factors to cell surfaces. These microcarriers hold great promise for the efficient expansion of cells for the industrial‐scale culture of therapeutic cells. In this article, multifunctional microcarriers for high‐throughput cell culture are engineered. These microcarriers support cell growth, have the ability to locally deliver biomolecules such as growth factors to the attached cells, and allow for subsequent cell harvesting via altered environmental temperature. These microcarriers are highly promising for industrial‐scale culture of therapeutic cells for cell‐based therapies and regenerative medicines.