Tricolor Visible Wavelength-Selective Hydrogels for Cell Encapsulation and Release

Over the past decade, photoresponsive biomaterials have birthed a surge of innovation in targeted drug delivery and 4D cell culture. Compared to other material-modifying stimuli (e.g., pH, enzymes, heat etc.), light is a particularly powerful stimulus for targeted drug delivery, uniquely affording spatiotemporal control in an orthogonally specified manner with different wavelengths. Despite its established promise in laboratory settings, significant challenges remain in pushing these technologies to the clinic. Current photosensitive materials are constrained by their reliance on high-energy UV light which is poorly penetrant through human tissue, limiting the depths to which they may be used for <i>in vivo</i> treatment. Additionally, photoresponsive materials developed thus far most typically respond to one or potentially two distinct wavelengths, thereby missing significant opportunities for reaction multiplexing by taking advantage of the entire spectrum of visible and IR light. <u>In this work, I will discuss our recent results in designing and synthesizing a series of visible light-responsive cytocompatible polymer crosslinkers for next-generation hydrogel photodegradation</u>. Translating well-established photochemistries of ruthenium polypyridyl complexes and <i>ortho</i>-nitrobenzyl moieties into the biomaterials space, we have created a series of crosslinkers that selectively respond to either red, green, or blue light. When incorporated within step-growth polymeric hydrogel networks, stable gels are formed that are highly sensitive to low-intensity visible light irradiation, reversing gelation within seconds through up to 2 cm of tissue. Reaction cytocompatibility ensures that cells in gels exhibit excellent viability throughout encapsulation, long-term culture, and photorecovery for downstream single-cell analysis. Permitting for the first time sequential photodegradation events deep within living tissue, we anticipate that these user-programmable biomaterial systems will pave a new and sustainable route to clinical drug delivery.