Design of synthetic extracellular matrices for probing breast cancer cell growth using robust cyctocompatible nucleophilic thiol-yne addition chemistry

Biomaterials
Laura J MacdougallAndrew P Dove

Abstract

Controlled, three-dimensional (3D) cell culture systems are of growing interest for both tissue regeneration and disease, including cancer, enabling hypothesis testing about the effects of microenvironment cues on a variety of cellular processes, including aspects of disease progression. In this work, we encapsulate and culture in three dimensions different cancer cell lines in a synthetic extracellular matrix (ECM), using mild and efficient chemistry. Specifically, harnessing the nucleophilic addition of thiols to activated alkynes, we have created hydrogel-based materials with multifunctional poly(ethylene glycol) (PEG) and select biomimetic peptides. These materials have definable, controlled mechanical properties (G' = 4-10 kPa) and enable facile incorporation of pendant peptides for cell adhesion, relevant for mimicking soft tissues, where polymer architecture allows tuning of matrix degradation. These matrices rapidly formed in the presence of sensitive breast cancer cells (MCF-7) for successful encapsulation with high cell viability, greatly improved relative to that observed with the more widely used radically-initiated thiol-ene crosslinking chemistry. Furthermore, controlled matrix degradation by both bulk and local m...Continue Reading

Citations

Nov 24, 2018·Macromolecular Rapid Communications·Hatice MutluPatrick Theato
Oct 17, 2019·Annals of Biomedical Engineering·Logan A NorthcuttMarjan Rafat
Jan 4, 2019·Tissue Engineering and Regenerative Medicine·Janarthanan Gopinathan, Insup Noh
Jul 10, 2020·Chemical Society Reviews·Maryam RahmatiHåvard J Haugen
Jan 14, 2021·Biomaterials Science·Kanishka FernandoEliza Li Shan Fong
Feb 3, 2021·Tissue Engineering. Part a·Trivia FrazierJeffrey M Gimble
Dec 23, 2021·Advanced Healthcare Materials·Katherine L WileyApril M Kloxin

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