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Enzymatic outside-in cross-linking enables single-step microcapsule production for high-throughput three-dimensional cell microaggregate formation

Van Loo, B ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1016/j.mtbio.2020.100047
  3. Publisher: Elsevier B.V , 2020
  4. Abstract:
  5. Cell-laden hydrogel microcapsules enable the high-throughput production of cell aggregates, which are relevant for three-dimensional tissue engineering and drug screening applications. However, current microcapsule production strategies are limited by their throughput, multistep protocols, and limited amount of compatible biomaterials. We here present a single-step process for the controlled microfluidic production of single-core microcapsules using enzymatic outside-in cross-linking of tyramine-conjugated polymers. It was hypothesized that a physically, instead of the conventionally explored biochemically, controlled enzymatic cross-linking process would improve the reproducibility, operational window, and throughput of shell formation. Droplets were flown through a silicone delay line, which allowed for highly controlled diffusion of the enzymatic cross-linking initiator. The microcapsules' cross-linking density and shell thickness is strictly depended on the droplet's retention time in the delay line, which is predictably controlled by flow rate. The here presented hydrogel cross-linking method allows for facile and cytocompatible production of cell-laden microcapsules compatible with the formation and biorthogonal isolation of long-term viable cellular spheroids for tissue engineering and drug screening applications. © 2020 The Author(s)
  6. Keywords:
  7. Cell encapsulation ; Cell spheroid ; Droplet microfluidics ; Enzymatic cross-linking ; Hollow microgel ; Hydrogel ; Amines ; Cells ; Conjugated polymers ; Controlled drug delivery ; Crosslinking ; Cytology ; Drops ; Hydrogels ; Microfluidics ; Microstructure ; Process control ; Screens (sizing) ; Silicones ; Throughput ; Tissue ; Tissue engineering ; Cell encapsulations ; Cell spheroids ; Controlled diffusion ; Cross-linking density ; Cross-linking process ; Microgel ; Single-step process ; Cell engineering
  8. Source: Materials Today Bio ; Volume 6 , 2020
  9. URL: https://www.sciencedirect.com/science/article/pii/S2590006420300077