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Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells

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Abstract

Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.

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Funding

This work was financially supported by the Oklahoma Center for the Advancement of Science and Technology. (Grant # HR13-214).

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Authors and Affiliations

  1. School of Chemical, Biological & Materials Engineering, Sarkeys Energy Center, 100 E Boyd St. Room T-301, Norman, OK, 73019, USA

    Aaron D. Simmons & Vassilios I. Sikavitsas

  2. Stephenson School of Biomedical Engineering, Carson Engineering Center, University of Oklahoma, 202 W Boyd St. Room 107, Norman, OK, 73019, USA

    Vassilios I. Sikavitsas

Authors
  1. Aaron D. Simmons
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  2. Vassilios I. Sikavitsas
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Correspondence to Vassilios I. Sikavitsas.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Simmons, A.D., Sikavitsas, V.I. Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells. Ann Biomed Eng 46, 37–47 (2018). https://doi.org/10.1007/s10439-017-1937-y

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  • DOI: https://doi.org/10.1007/s10439-017-1937-y

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