Self-Healing Boronic Acid-Based Hydrogels for 3D Co-cultures

• Published in: ACS macro letters Vol. 7; no. 9; pp. 1105 - 1110
• Main Authors: Smithmyer, Megan E, Deng, Christopher C, Cassel, Samantha E, LeValley, Paige J, Sumerlin, Brent S, Kloxin, April M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-09-2018
• ISSN: 2161-1653; 2161-1653
• DOI: 10.1021/acsmacrolett.8b00462

Synthetic hydrogels have been widely adopted as well-defined matrices for three-dimensional (3D) cell culture, with increasing interest in systems that enable the co-culture of multiple cell types for probing both cell–matrix and cell–cell interactions in studies of tissue regeneration and disease. We hypothesized that the unique dynamic covalent chemistry of self-healing hydrogels could be harnessed for not only the encapsulation and culture of human cells but also the subsequent construction of layered hydrogels for 3D co-cultures. To test this, we formed hydrogels using boronic acid-functionalized polymers and demonstrated their self-healing in the presence of physiologically relevant cell culture media. Two model human cell lines, MDA-MB-231 breast cancer cells and CCL151 pulmonary fibroblasts, were encapsulated within these dynamic materials, and good viability was observed over time. Finally, self-healing of cut hydrogel “blocks” laden with these different cell types was used to create layered hydrogels for the generation of a dynamic co-culture system. This work demonstrates the utility of self-healing materials for multidimensional cultures and establishes approaches broadly useful for a variety of biological applications.