Gasotransmitter delivery for bone diseases and regeneration

<p>Endogenous gaseous signaling molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S), collectively called gasotransmitters, regulate various physiological and pathophysiological processes. Thus, they offer significant advantages over traditional small-molecule drugs in treating bone diseases. However, their clinical use is limited by their gaseous nature, extensive reactivity, and short half-life. Also, these gasotransmitters behave as a double-edged sword, providing therapeutic effects at physiological concentrates while exhibiting acute toxicity at high concentrations. Therefore, controlled, sustained, and even targeted delivery of gasotransmitters is highly desirable. In this review, we emphasize recent significant advances in gasotransmitter delivery materials, including the gas-releasing molecules and their delivery platforms. We further focus on the therapeutic application of these gasotransmitters in treating bone diseases, including implant-associate infection, immunomodulation, bone regeneration, osteoporosis, and arthritis, aiming to provide references for the development of novel therapeutic strategies for bone diseases.</p>