Non-destructive detection of matrix stabilization correlates with enhanced mechanical properties of self-assembled articular cartilage

Anne K. Haudenschild, Benjamin E. Sherlock, Xiangnan Zhou, Jerry C. Hu, J. Kent Leach, Laura Marcu, Kyriacos A Athanasiou

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Tissue engineers rely on expensive, time-consuming, and destructive techniques to monitor the composition, microstructure, and function of engineered tissue equivalents. A non-destructive solution to monitor tissue quality and maturation would greatly reduce costs and accelerate the development of tissue-engineered products. The objectives of this study were to (a) determine whether matrix stabilization with exogenous lysyl oxidase-like protein-2 (LOXL2) with recombinant hyaluronan and proteoglycan link protein-1 (LINK) would result in increased compressive and tensile properties in self-assembled articular cartilage constructs, (b) evaluate whether label-free, non-destructive fluorescence lifetime imaging (FLIm) could be used to infer changes in both biochemical composition and biomechanical properties, (c) form quantitative relationships between destructive and non-destructive measurements to determine whether the strength of these correlations is sufficient to replace destructive testing methods, and (d) determine whether support vector machine (SVM) learning can predict LOXL2-induced collagen crosslinking. The combination of exogenous LOXL2 and LINK proteins created a synergistic 4.9-fold increase in collagen crosslinking density and an 8.3-fold increase in tensile strength as compared with control (CTL). Compressive relaxation modulus was increased 5.9-fold with addition of LOXL2 and 3.4-fold with combined treatments over CTL. FLIm parameters had strong and significant correlations with tensile properties (R 2  = 0.82; p < 0.001) and compressive properties (R 2  = 0.59; p < 0.001). SVM learning based on FLIm-derived parameters was capable of automating tissue maturation assessment with a discriminant ability of 98.4%. These results showed marked improvements in mechanical properties with matrix stabilization and suggest that FLIm-based tools have great potential for the non-destructive assessment of tissue-engineered cartilage.

Original languageEnglish (US)
JournalJournal of Tissue Engineering and Regenerative Medicine
StatePublished - Jan 1 2019


  • autofluorescence
  • biomechanics
  • cartilage
  • imaging
  • non-destructive monitoring
  • tissue engineering

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


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