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The influence of chondrocyte source on the manufacturing reproducibility of human tissue engineered cartilage

Cornell Affiliated Author(s)

Author

J.M. Middendorf
N. Diamantides
B. Kim
C. Dugopolski
S. Kennedy
E. Blahut
Itai Cohen
L.J. Bonassar

Abstract

Multiple human tissue engineered cartilage constructs are showing promise in advanced clinical trials but identifying important measures of manufacturing reproducibility remains a challenge. FDA guidance suggests measuring multiple mechanical properties prior to implantation, because these properties could affect the long term success of the implant. Additionally, these engineered cartilage mechanics could be sensitive to the autologous chondrocyte source, an inherently irregular manufacturing starting material. If any mechanical properties are sensitive to changes in the autologous chondrocyte source, these properties may need to be measured prior to implantation to ensure manufacturing reproducibility and quality. Therefore, this study identified variability in the compressive, friction, and shear properties of a human tissue engineered cartilage constructs due to the chondrocyte source. Over 200 constructs were created from 7 different chondrocyte sources and tested using 3 distinct mechanical experiments. Under confined compression, the compressive properties (aggregate modulus and hydraulic permeability) varied by orders of magnitude due to the chondrocyte source. The friction coefficient changed by a factor of 5 due to the chondrocyte source and high intrapatient variability was noted. In contrast, the shear modulus was not affected by changes in the chondrocyte source. Finally, measurements on the local compressive and shear mechanics revealed variability in the depth dependent strain fields based on chondrocyte source. Since the chondrocyte source causes large amounts of variability in the compression and local mechanical properties of engineered cartilage, these mechanical properties may be important measures of manufacturing reproducibility. Statement of significance: Although the FDA recommends measuring mechanical properties of human tissue engineered cartilage constructs during manufacturing, the effect of manufacturing variability on construct mechanics is unknown. As one of the first studies to measure multiple mechanical properties on hundreds of human tissue engineered cartilage constructs, we found the compressive properties are most sensitive to changes in the autologous chondrocyte source, an inherently irregular manufacturing variable. This sensitivity to the autologous chondrocyte source reveals the compressive properties should be measured prior to implantation to assess manufacturing reproducibility. © 2021

Date Published

Journal

Acta Biomaterialia

Volume

131

Number of Pages

276-285,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85111018009&doi=10.1016%2fj.actbio.2021.07.003&partnerID=40&md5=2a71036f65cb4fa531cfeb53a5504266

DOI

10.1016/j.actbio.2021.07.003

Research Area

Group (Lab)

Itai Cohen Group

Funding Source

BMMB-153646
DGE-1650441
DMR-1807602

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