Cross‐linking affects cellular condensation and chondrogenesis in type II collagen‐GAG scaffolds seeded with bone marrow‐derived mesenchymal stem cells |
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| Authors: | Scott M. Vickers Tobias Gotterbarm Myron Spector |
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| Affiliation: | 1. Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139;2. Tissue Engineering, VA Boston Healthcare System, Boston Campus, Room D1‐152, Mail Stop: 151 Research, 150 S. Huntington Ave., Boston, Massachusetts 02130;3. Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115;4. Stiftung Orthop?dische Universit?tsklinik Heidelberg, Heidelberg 69118, Germany |
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| Abstract: | The formation of cartilaginous tissue by chondroprogenitor cells, whether in vivo or in vitro, appears to require a critical initial stage of “condensation” in which intercellular space is reduced through an aggregation of cells, leading to development of cell‐to‐cell junctions followed by chondrocytic differentiation. The objective of this study was to investigate the association of aggregation (condensation) of mesenchymal stem cell (MSCs) and chondrogenesis in vitro. Previous work with chondrocytes indicated that the cross‐link density and related cell‐mediated contraction of collagen scaffolds significantly affects cartilaginous tissue formation within the cell‐seeded construct. Based on this finding, we hypothesized that the cell‐aggregating effect of the contraction of MSC‐seeded collagen scaffolds of lower cross‐link density favors chondrogenesis; scaffolds of higher cross‐link density, which resist cell‐mediated contraction, would demonstrate a lower cell number density (i.e., subcritical packing density) and less cartilage formation. Type II collagen–GAG scaffolds, chemically cross‐linked to achieve a range of cross‐link densities, were seeded with caprine MSCs and cultured for 4 weeks. Constructs with low cross‐link densities experienced cell‐mediated contraction, increased cell number densities, and a greater degree of chondrogenesis (indicated by the chondrocytic morphology of cells, and synthesis of GAG and type II collagen) compared to more highly cross‐linked scaffolds that resisted cellular contraction. These results provide a foundation for further investigation of the mechanisms by which condensation of mesenchymal cells induces chondrogenesis in this in vitro model, and may inform cross‐linking protocols for collagen scaffolds for use in cartilage tissue engineering. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1184–1192, 2010 |
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| Keywords: | stem cells chondrogenesis tissue engineering condensation collagen scaffolds |
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