Biorheology 43 (2006) 497–507 IOS Press
497
Dynamic deformational loading results in selective application of mechanical stimulation in a layered, tissue-engineered cartilage construct
Kenneth W. Ng a , Robert L. Mauck a, , Lauren Y. Statman a , Evan Y. Lin a , Gerard A. Ateshian b and Clark T. Hung a,
Cellular Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA b Musculoskeletal Biomechanics Laboratory, Departments of Biomedical and Mechanical Engineering, Columbia University, New York, NY, USA
Abstract. The application of dynamic physiologic loading to a bilayered chondrocyte-seeded agarose construct with a 2% (wt/vol) top layer and 3% (wt/vol) bottom layer was hypothesized to (1) improve overall construct properties and (2) result in a tissue that mimics the mechanical inhomogeneity of native cartilage. Dynamic loading over the 28 day culture period was found to signicantly increase bulk mechanical and biochemical properties versus free-swelling culture. The initial depth-distribution of the compressive Young's modulus (EY ) reected the intrinsic properties of the gel in each layer and a similar trend to the native tissue, with a softer 2% gel layer and a much stiffer 3% gel layer. After 28 days in culture, free-swelling conditions maintained this general trend while loaded constructs possessed a reverse prole, with signicant increases in EY observed only in the 2% gel. Histological analysis revealed preferential matrix formation in the 2% agarose layer, with matrix localized more pericellularly in the 3% agarose layer. Finite element modeling revealed that, prior to signicant matrix elaboration, the 2% layer experiences increased mechanical stimuli (uid ow and compressive strain) during loading that may enhance chondrocyte stimulation and nutrient transport in that layer, consistent with experimental observations. From these results, we conclude that due to the limitations in 3% agarose, the use of this type of bilayered construct to construct depth-dependent inhomogeneity similar to the native tissue is not likely to be successful under long-term culture conditions. Our study underscores the importance of other physical properties of the scaffold that may have a greater inuence on interconnected tissue formation than intrinsic scaffold stiffness. Keywords: Cartilage, tissue engineering, inhomogeneity, digital image correlation, agarose, scaffold design
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