Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival.

Though crucial for natural bone healing, local calcium ion (Ca 2+ ) and phosphate ion (P i ) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H 2 S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca 2+ /P i concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H 2 S donor, were applied to assess the influence of H 2 S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca 2+ (32 mM) and/or P i (16 mM). To controllably deliver H 2 S over time, a novel donor molecule (thioglutamic acid-GluSH) was synthesized and evaluated for its H 2 S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H 2 S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca 2+ /P i concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H 2 S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications.