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Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival.

Soheila Ali Akbari Ghavimi1, Trent J Faulkner1, Rama Rao Tata1

  • 1Department of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211, USA.

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Hydrogen sulfide (H2S) protects mesenchymal stem cells (MSCs) from toxic calcium and phosphate levels in bone healing. A novel H2S donor, GluSH, supports MSCs and osteoblast differentiation for bone tissue engineering.

Keywords:
bone regenerationcalcium phosphatecytoprotectionhydrogen sulfidemesenchymal stem cells

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Cell Biology

Background:

  • High local calcium (Ca2+) and phosphate (Pi) concentrations are vital for bone healing but can become cytotoxic.
  • This cytotoxicity leads to mitochondrial dysfunction, oxidative stress, and cell death in mesenchymal stem cells (MSCs).
  • Hydrogen sulfide (H2S) shows potential as a cytoprotective agent to improve MSC tolerance in bone tissue engineering.

Purpose of the Study:

  • To evaluate the cytoprotective effects of H2S on MSCs exposed to cytotoxic Ca2+/Pi concentrations.
  • To determine the optimal concentration of a fast-releasing H2S donor (NaSH) for MSC proliferation.
  • To synthesize and assess a novel sustained-release H2S donor (thioglutamic acid-GluSH) for bone regenerative applications.

Main Methods:

  • Assessed MSC proliferation and differentiation under varying NaSH concentrations.
  • Determined the cytotoxic limit of NaSH for MSCs.
  • Synthesized GluSH and characterized its H2S release profile over 7 days.
  • Evaluated MSC viability and osteogenic differentiation in the presence of cytotoxic Ca2+/Pi and GluSH.

Main Results:

  • A NaSH concentration of 1 mM enhanced MSC proliferation and differentiation, with a toxicity limit observed at 4 mM.
  • The novel donor molecule, GluSH, successfully released H2S at cytoprotective levels for 7 days.
  • MSCs cultured with cytotoxic Ca2+/Pi and GluSH demonstrated enhanced survival and osteogenic differentiation.

Conclusions:

  • H2S, particularly from sustained donors like GluSH, can protect MSCs from cytotoxic ion concentrations.
  • GluSH shows promise for incorporation into calcium phosphate (CaP)-based bone graft substitutes.
  • This approach offers a viable strategy for enhancing bone regeneration in complex applications.