Hydrogels for Gasotransmitter Delivery: Nitric oxide, carbon monoxide, and hydrogen sulfide

Gasotransmitters, gaseous signaling molecules including Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), maintain myriad physiological processes. Low levels of gasotransmitters are often associated with specific problems or diseases, so NO, CO, and H2S hold potential in treating bacterial infections, chronic wounds, myocardial infarction, ischemia, and various other diseases. However, their clinical applications as therapeutic agents are limited due to their gaseous nature, short half-life, and broad physiological roles. One route toward the greater application of gasotransmitters in medicine is through localized delivery. Hydrogels are attractive biomedical materials for the controlled release of embedded therapeutics as they are typically biocompatible, possess high water content, have tunable mechanical properties, and are injectable in certain cases. Hydrogel-based gasotransmitter delivery systems began with NO, and hydrogels for CO and H2S have appeared over the last decade. In this review, we highlight the biological importance of gasotransmitters and discuss the fabrication of hydrogel materials, distinguishing between methods used to physically encapsulate small molecule gasotransmitter donor compounds or chemically tether them to a hydrogel scaffold. We also detail the release behavior and potential therapeutic applications of recently reported gasotransmitter-releasing hydrogels. Finally, we envision what the future of this field might hold and describe challenges that need to be addressed moving forward.