Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond

Gaseous mediators are increasingly recognized as critical regulators of human physiology and pathology, offering unique therapeutic opportunities that are fundamentally constrained by challenges in controlled delivery, spatial targeting, and biological specificity when harnessed through advanced delivery technologies. Among them, nitric oxide (NO) has emerged as a central player. Recent advancements have transitioned from conventional donor-based systems with limited control over dose and localization to wearable gas-delivery platforms capable of real-time, patient-specific dosing and frequently coupling with embedded diagnostic functionalities for dynamic feedback and precision control. Importantly, the therapeutic scope of gas biology is expanding beyond NO to encompass other clinically relevant and emerging gases, including O₂, CO, H₂S, H₂, CO₂, SO₂, and Xe. These gases exhibit multifaceted biological effects ranging from cytoprotection and vasoregulation to antimicrobial and anti-inflammatory actions, thereby necessitating innovative material-based and bioresponsive delivery strategies that can interface dynamically with biological systems. By critically assessing progress in material platforms, responsive release mechanisms, and multimodal delivery approaches, this review bridges fundamental gas biology with clinically translatable therapeutic design. We further highlight persistent translational bottlenecks, such as dose control, off-target effects, and long-term safety, while outlining emerging research pathways poised to define the next era of gas-based medicine.