Enzymatic outside-in cross-linking enables single-step microcapsule production for high-throughput three-dimensional cell microaggregate formation.
Cell encapsulation
Cell spheroid
Droplet microfluidics
Enzymatic cross-linking
Hollow microgel
Hydrogel
Journal
Materials today. Bio
ISSN: 2590-0064
Titre abrégé: Mater Today Bio
Pays: England
ID NLM: 101757228
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
02
01
2020
revised:
18
02
2020
accepted:
19
02
2020
entrez:
18
4
2020
pubmed:
18
4
2020
medline:
18
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32300754
doi: 10.1016/j.mtbio.2020.100047
pii: S2590-0064(20)30007-7
pii: 100047
pmc: PMC7152680
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100047Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Control Release. 2011 May 30;152(1):186-95
pubmed: 21291927
Small. 2012 Aug 6;8(15):2356-60
pubmed: 22648761
Angew Chem Int Ed Engl. 2005 Jan 21;44(5):724-8
pubmed: 15612064
Macromol Biosci. 2016 Oct;16(10):1524-1532
pubmed: 27440382
Biomaterials. 2009 Jul;30(20):3371-7
pubmed: 19345991
Eur Cell Mater. 2008 Dec 19;16:92-9
pubmed: 19101892
Nat Mater. 2011 Sep 04;10(11):877-83
pubmed: 21892177
Biomaterials. 2012 May;33(15):3835-45
pubmed: 22369963
Acta Biomater. 2014 Jun;10(6):2551-62
pubmed: 24590158
Acta Biomater. 2014 Jun;10(6):2539-50
pubmed: 24561710
Biomed Microdevices. 2015 Apr;17(2):33
pubmed: 25681969
Adv Mater. 2011 Mar 25;23(12):H90-4
pubmed: 21360782
Cytotechnology. 2007 Jul;54(3):135-43
pubmed: 19003005
Biomaterials. 2012 Apr;33(12):3446-55
pubmed: 22306021
Stem Cell Reports. 2017 Mar 14;8(3):758-772
pubmed: 28196691
Biomaterials. 2009 May;30(13):2544-51
pubmed: 19176242
Eur Cell Mater. 2012 Jun 05;23:387-99
pubmed: 22665161
J Biosci Bioeng. 2007 May;103(5):389-98
pubmed: 17609152
Small. 2017 Jun;13(22):
pubmed: 28452168
Biomaterials. 2009 Oct;30(30):5937-42
pubmed: 19656563
J Cell Sci. 2012 Jul 1;125(Pt 13):3015-24
pubmed: 22797912
Lab Chip. 2019 Jun 7;19(11):1977-1984
pubmed: 31017163
Lab Chip. 2013 Dec 7;13(23):4525-33
pubmed: 24113543
J Biotechnol. 2015 Jul 10;205:14-23
pubmed: 25746901
Biomaterials. 2013 Sep;34(29):7097-105
pubmed: 23800741
J Mater Chem B. 2017 Jul 7;5(25):4835-4844
pubmed: 32263999
Lab Chip. 2016 Apr 21;16(8):1346-9
pubmed: 26999495
Nat Protoc. 2009;4(3):309-24
pubmed: 19214182
Prog Polym Sci. 2012 Jan;37(1):106-126
pubmed: 22125349
Nat Commun. 2019 Sep 25;10(1):4347
pubmed: 31554812
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14843-8
pubmed: 23980147
Nat Rev Mol Cell Biol. 2014 Oct;15(10):647-64
pubmed: 25237826
Biotechnol Prog. 2013 Nov-Dec;29(6):1528-34
pubmed: 23955874
Sci Rep. 2016 Nov 03;6:36011
pubmed: 27808102
Lab Chip. 2011 Jan 21;11(2):246-52
pubmed: 20967338
Acta Biomater. 2007 Jul;3(4):495-501
pubmed: 17275429
Nature. 2006 Jul 27;442(7101):368-73
pubmed: 16871203
Adv Healthc Mater. 2019 Nov;8(22):e1901221
pubmed: 31603632
Adv Drug Deliv Rev. 2014 Apr;69-70:29-41
pubmed: 24636868
J Control Release. 2015 Oct 10;215:39-54
pubmed: 26220617
Free Radic Biol Med. 2010 Nov 1;49(8):1298-305
pubmed: 20673847