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

The importance of hydrogen sulfide (H2S) 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 H2S 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 H2S achieved encouraging results in preclinical studies in the treatment of systemic bone diseases, such as osteoporosis; however, a local delivery of H2S at sites of bone damage may provide additional opportunities of treatment. Here, we highlight how H2S 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 H2S-donors with improved features, laying the ground for the development of H2S-releasing devices for bone regenerative medicine. This review is intended to give a state-of-the-art description of the pro-regenerative properties of H2S, with a focus on bone tissue, and to discuss the potential of H2S-releasing scaffolds as a support for bone repair.