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The importance of hydrogen sulfide (H 2 S) in the regulation of multiple physiological functions has been clearly recognized in the over 20 years since it was first identified as a novel gasotransmitter. In bone tissue H 2 S exerts a cytoprotective effect and promotes bone formation. Just recently, the scientific community has begun to appreciate its role as a therapeutic agent in bone pathologies. Pharmacological administration of H 2 S achieved encouraging results in preclinical studies in the treatment of systemic bone diseases, such as osteoporosis; however, a local delivery of H 2 S at sites of bone damage may provide additional opportunities of treatment. Here, we highlight how H 2 S stimulates multiple signaling pathways involved in various stages of the processes of bone repair. Moreover, we discuss how material science and chemistry have recently developed biomaterials and H 2 S-donors with improved features, laying the ground for the development of H 2 S-releasing devices for bone regenerative medicine. This review is intended to give a state-of-the-art description of the pro-regenerative properties of H 2 S, with a focus on bone tissue, and to discuss the potential of H 2 S-releasing scaffolds as a support for bone repair.

Hydrogen Sulfide in Bone Tissue Regeneration and Repair: State of the Art and New Perspectives