title: One-step generation of cell-laden microgels using double emulsion drops with a sacrificial ultra-thin oil shell.
abstract: Cell-laden microgels with highly uniform sizes have significant potential in tissue engineering and cell therapy due to their capability to provide a physiologically relevant three-dimensional (3D) microenvironment for living cells. In this work, we present a simple and efficient microfluidic approach to produce monodisperse cell-laden microgels through the use of double emulsion drops with an ultra-thin oil shell as the sacrificial template. Specifically, the thin oil shell in double emulsion spontaneously dewets upon polymerization of the innermost precursor drop and subsequent transfer into an aqueous solution, resulting in direct dispersion of microgels in the aqueous phase. Compared to conventional single emulsion-based techniques for cell encapsulation, this one-step approach prevents prolonged exposure of cells to the oil phase, leading to high-throughput cell encapsulation in microgels without compromising the cell viability. Moreover, this approach allows us to culture cells within a 3D microgel which mimics the extracellular matrix, thus enabling long-term cell functionality. This microfluidic technique represents a significant step forward in high-throughput cell microencapsulation technology and offers a potentially viable option to produce cell-laden microgels for widespread applications in tissue engineering and cell therapies.
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu.
authors.forename: Chang-Hyung
authors.initials: CH
authors.lastname: Choi
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu and School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116023, PR China.
authors.forename: Huanan
authors.initials: H
authors.lastname: Wang
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu.
authors.forename: Hyomin
authors.initials: H
authors.lastname: Lee
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu.
authors.forename: June Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Mao
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. weitz@seas.harvard.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002470:Cell Survival; D018914:Cells, Immobilized / Q000166:cytology*; D060833:Cellular Microenvironment; D004285:Dogs; D004655:Emulsions; D004987:Ethers / Q000737:chemistry; D005240:Feasibility Studies; D017611:Fluorine Compounds / Q000737:chemistry; D006801:Humans; D020100:Hydrogels; D057927:Hydrophobic and Hydrophilic Interactions; D020014:K562 Cells; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D044085:Microfluidics / Q000295:instrumentation*; D008899:Mineral Oil / Q000737:chemistry; D041681:NIH 3T3 Cells; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation
chemical_list: D001672:Biocompatible Materials; D004655:Emulsions; D004987:Ethers; D017611:Fluorine Compounds; C472825:HFE-7500; D020100:Hydrogels; D013501:Surface-Active Agents; D008899:Mineral Oil