Engineering PEG-based hydrogels to foster efficient endothelial network formation in free-swelling and confined microenvironments.
Endothelial cells
Microvascular network
Swelling
Synthetic hydrogel
poly(ethylene glycol)
poly(propargyl-l-glutamate)
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
03
10
2019
revised:
22
02
2020
accepted:
25
02
2020
pubmed:
17
3
2020
medline:
15
5
2021
entrez:
16
3
2020
Statut:
ppublish
Résumé
In vitro tissue engineered models are poised to have significant impact on disease modeling and preclinical drug development. Reliable methods to induce microvascular networks in such microphysiological systems are needed to improve the size and physiological function of these models. By systematically engineering several physical and biomolecular properties of the cellular microenvironment (including crosslinking density, polymer density, adhesion ligand concentration, and degradability), we establish design principles that describe how synthetic matrix properties influence vascular morphogenesis in modular and tunable hydrogels based on commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. We apply these design principles to generate endothelial networks that exhibit consistent morphology throughout depths of hydrogel greater than 1 mm. These PEG8a-based hydrogels have relatively high volumetric swelling ratios (>1.5), which limits their utility in confined environments such as microfluidic devices. To overcome this limitation, we mitigate swelling by incorporating a highly functional PEG-grafted alpha-helical poly (propargyl-l-glutamate) (PPLGgPEG) macromer along with the canonical 8-arm PEG8a macromer in gel formation. This hydrogel platform supports enhanced endothelial morphogenesis in neutral-swelling environments. Finally, we incorporate PEG8a-PPLGgPEG gels into microfluidic devices and demonstrate improved diffusion kinetics and microvascular network formation in situ compared to PEG8a-based gels.
Identifiants
pubmed: 32172030
pii: S0142-9612(20)30167-8
doi: 10.1016/j.biomaterials.2020.119921
pmc: PMC7203641
mid: NIHMS1575392
pii:
doi:
Substances chimiques
Biocompatible Materials
0
Hydrogels
0
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
119921Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008334
Pays : United States
Organisme : NIBIB NIH HHS
ID : U01 EB029132
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
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