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Modeling and experimental methods to predict oxygen distribution in bone defects following cell transplantation

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Abstract

We have developed a mathematical model that allows simulation of oxygen distribution in a bone defect as a tool to explore the likely effects of local changes in cell concentration, defect size or geometry, local oxygen delivery with oxygen-generating biomaterials (OGBs), and changes in the rate of oxygen consumption by cells within a defect. Experimental data for the oxygen release rate from an OGB and the oxygen consumption rate of a transplanted cell population are incorporated into the model. With these data, model simulations allow prediction of spatiotemporal oxygen concentration within a given defect and the sensitivity of oxygen tension to changes in critical variables. This information may help to minimize the number of experiments in animal models that determine the optimal combinations of cells, scaffolds, and OGBs in the design of current and future bone regeneration strategies. Bone marrow-derived nucleated cell data suggest that oxygen consumption is dependent on oxygen concentration. OGB oxygen release is shown to be a time-dependent function that must be measured for accurate simulation. Simulations quantify the dependency of oxygen gradients in an avascular defect on cell concentration, cell oxygen consumption rate, OGB oxygen generation rate, and OGB geometry.

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Acknowledgments

This work was supported by National Institutes of Health T32 AR050959, the Cleveland Clinic Foundation, and the Armed Forces Institute of Regenerative Medicine (AFIRM). AFIRM is managed and funded through the US Army Medical Research and Materiel Command (MRMC). The AFIRM has additional funding from the US Navy, the Office of Naval Research, the US Air Force Office of the Surgeon General, the National Institutes of Health, the Veterans Administration, the Cleveland Clinic, and local public and private matching funds. The AFIRM contribution to this publication was supported by a subcontract from Rutgers University, Department of Chemistry and Chemical Biology/NJ Center for Biomaterials, under Cooperative Agreement No. WSIXWH-08-2-0034 from the US Department of Defense, US Army Medical Research Acquisition.

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No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave ND20, Cleveland, OH, 44195, USA

    Christopher M. Heylman & George F. Muschler

  2. Department of Biomedical Engineering, Case Western Reserve University, 319 Wickenden Building, 10900 Euclid Ave, Cleveland, OH, 44106, USA

    Christopher M. Heylman, Sharon Santoso, Melissa D. Krebs, Gerald M. Saidel & Eben Alsberg

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  1. Christopher M. Heylman
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  2. Sharon Santoso
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  3. Melissa D. Krebs
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  4. Gerald M. Saidel
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  6. George F. Muschler
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Correspondence to Christopher M. Heylman.

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Heylman, C.M., Santoso, S., Krebs, M.D. et al. Modeling and experimental methods to predict oxygen distribution in bone defects following cell transplantation. Med Biol Eng Comput 52, 321–330 (2014). https://doi.org/10.1007/s11517-013-1133-7

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  • DOI: https://doi.org/10.1007/s11517-013-1133-7

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