Document Type

Article

Version Deposited

Published Version

Publication Date

12-1-2018

Publication Title

Nature Communications

DOI

10.1038/s41467-018-03021-5

Abstract

3D microenvironmental parameters control cell behavior, but can be challenging to investigate over a wide range of conditions. Here, a combinatorial hydrogel platform is developed that uses light-mediated thiol-norbornene chemistry to encapsulate cells within hydrogels with biochemical gradients made by spatially varied light exposure. Specifically, mesenchymal stem cells are photoencapsulated in norbornene-modified hyaluronic acid hydrogels functionalized with gradients (0–5 mM) of peptides that mimic cell-cell or cell-matrix interactions, either as single or orthogonal gradients. Chondrogenesis varied spatially in these hydrogels based on the local biochemical formulation, as indicated by Sox9 and aggrecan expression levels. From 100 combinations investigated, discrete hydrogels are formulated and early gene expression and long-term cartilage-specific matrix production are assayed and found to be consistent with screening predictions. This platform is a scalable, highthroughput technique that enables the screening of the effects of multiple biochemical signals on 3D cell behavior.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2018

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Published Citation

Vega, S.L., Kwon, M., Song, K., Wang, C., Mauck, R., Han, L., & Burdick, J. (2018). Combinatorial hydrogels with biochemical gradients for screening 3D cellular microenvironments. Nature Communications, 9:614.

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