4th Annual Mountain West
Biomedical Engineering Conference

Since its conception by Sharpless in 2001, “click chemistry” has promised extremely selective and fully orthogonal reactions that proceed with high efficiency and under a variety of mild conditions. Functional molecules can be easily synthesized via these independently modular reactions and ultimately incorporated into materials with highly defined properties. Though these versatile click reactions have been broadly exploited in many fields including drug discovery, material science, and bioconjugation, the intrinsic toxicity of their synthetic schemes has limited their application in biologically-based systems. This work introduces a robust synthetic strategy where multifunctional macromolecular precursors react via a copper-free click chemistry, enabling the direct encapsulation of cells within click hydrogels for the first time. The step-growth nature of this polymerization process provides ideal network structures with minimal defects and local heterogeneities, ensuring that each cell experiences initially identical material properties. These local properties can be then altered at user-dictated locations in space and time via an orthogonal thiol-ene photocoupling click chemistry that facilitates patterning of biological functionalities within the gel, ultimately providing tailorability of the physical and chemical properties of the cell culture niche in situ. These local manipulations of the gel microenvironment provide an avenue to introduce chemical cues that direct cell function and/or assay cell behavior throughout specific regions within the material. These functionalization reactions are completed in minutes, allowing for real-time manipulation of the cell microenvironment in 3D.