期刊
MATERIALS TODAY BIO
卷 6, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mtbio.2020.100047
关键词
Cell encapsulation; Droplet microfluidics; Enzymatic cross-linking; Hydrogel; Hollow microgel; Cell spheroid
资金
- Innovative Research Incentives Scheme Vidi from the Netherlands Organization for Scientific Research (NWO) [17522]
- European Research Council (ERC) [759425]
- Dutch Arthritis Foundation [17-1-405]
- Iran National Science Foundation: INSF [95827599]
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.
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