Patterning Three-Dimensional Hydrogel Microenvironments Using Hyperbranched Polyglycerols for Independent Control of Mesh Size and Stiffness

• Published in: Biomacromolecules 2017-04, Vol.18 (4), p.1393-1400
• Main Authors: Pedron, Sara, Pritchard, Amanda M, Vincil, Gretchen A, Andrade, Brenda, Zimmerman, Steven C, Harley, Brendan A. C
• Format: Article
• Language: English
• Subjects: Animals; biochemical compounds; Biochemical Phenomena; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Biophysical Phenomena; cell culture; Cell Culture Techniques; Cell Proliferation - physiology; Cell Survival - physiology; Cells, Cultured; chemical bonding; Cross-Linking Reagents - chemistry; crosslinking; diffusivity; Elastic Modulus; encapsulation; extracellular matrix; Extracellular Matrix - chemistry; Glycerol - chemical synthesis; Glycerol - chemistry; hydrogels; Hydrogels - chemical synthesis; Hydrogels - chemistry; mechanical properties; microstructure; Molecular Structure; polyethylene glycol; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polymers - chemical synthesis; Polymers - chemistry; Stem Cells - cytology; Swine
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/acs.biomac.7b00118

The extracellular matrix is an environment rich with structural, mechanical, and molecular signals that can impact cell biology. Traditional approaches in hydrogel biomaterial design often rely on modifying the concentration of cross-linking groups to adjust mechanical properties. However, this strategy provides limited capacity to control additional important parameters in 3D cell culture such as microstructure and molecular diffusivity. Here we describe the use of multifunctional hyperbranched polyglycerols (HPGs) to manipulate the mechanical properties of polyethylene glycol (PEG) hydrogels while not altering biomolecule diffusion. This strategy also provides the ability to separately regulate spatial and temporal distribution of biomolecules tethered within the hydrogel. The functionalized HPGs used here can also react through a copper-free click chemistry, allowing for the encapsulation of cells and covalently tethered biomolecules within the hydrogel. Because of the hyperbranched architecture and unique properties of HPGs, their addition into PEG hydrogels affords opportunities to locally alter hydrogel cross-linking density with minimal effects on global network architecture. Additionally, photocoupling chemistry allows micropatterning of bioactive cues within the three-dimensional gel structure. This approach therefore enables us to tailor mechanical and diffusive properties independently while further allowing for local modulation of biomolecular cues to create increasingly complex cell culture microenvironments.