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Ultrasound Elastography for Estimation of Regional Strain of Multilayered Hydrogels and Tissue-Engineered Cartilage

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Abstract

Tissue-engineered (TE) cartilage constructs tend to develop inhomogeneously, thus, to predict the mechanical performance of the tissue, conventional biomechanical testing, which yields average material properties, is of limited value. Rather, techniques for evaluating regional and depth-dependent properties of TE cartilage, preferably non-destructively, are required. The purpose of this study was to build upon our previous results and to investigate the feasibility of using ultrasound elastography to non-destructively assess the depth-dependent biomechanical characteristics of TE cartilage while in a sterile bioreactor. As a proof-of-concept, and to standardize an assessment protocol, a well-characterized three-layered hydrogel construct was used as a surrogate for TE cartilage, and was studied under controlled incremental compressions. The strain field of the construct predicted by elastography was then validated by comparison with a poroelastic finite-element analysis (FEA). On average, the differences between the strains predicted by elastography and the FEA were within 10%. Subsequently engineered cartilage tissue was evaluated in the same test fixture. Results from these examinations showed internal regions where the local strain was 1–2 orders of magnitude greater than that near the surface. These studies document the feasibility of using ultrasound to evaluate the mechanical behaviors of maturing TE constructs in a sterile environment.

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Acknowledgments

Research reported in this publication was supported by the National Institute of Biomedical imaging and Bioengineering under award number R01 EB20367-01, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Awards Number P01 AR053622 (JMM, JFW, HB) and AR050208 (JFW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr. Joseph Heebner was the recipient of an ENGAGE fellowship. Funding for ENGAGE 2013 came from the National Center for Regenerative Medicine (http://www.ncrm.us) and proceeds from MSC2011 conference (http://www.mscconference.net). We thank Alexander Lee Rivera for help with scaffold fabrication. The authors have no financial relationships that may cause a conflict of interest. We thank Dr. Victor M. Goldberg, to whom this paper is dedicated, for his interest and encouragement, and for providing the seed money for these studies.

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Correspondence to Joseph M. Mansour.

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Associate Editor Eric M. Darling oversaw the review of this article.

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Chung, CY., Heebner, J., Baskaran, H. et al. Ultrasound Elastography for Estimation of Regional Strain of Multilayered Hydrogels and Tissue-Engineered Cartilage. Ann Biomed Eng 43, 2991–3003 (2015). https://doi.org/10.1007/s10439-015-1356-x

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