期刊
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
卷 11, 期 -, 页码 27-40出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jmbbm.2011.12.004
关键词
Relative density; Collagen; Scaffold; Tendon; Gene expression
资金
- NIGMS NIH HHS [T32 GM070421, T32GM070421] Funding Source: Medline
Biomaterials for orthopedic tissue engineering must balance mechanical and bioactivity concerns. This work describes the fabrication of a homologous series of anisotropic collagen-GAG (CG) scaffolds with aligned tracks of ellipsoidal pores but increasing relative densities (rho*/rho s), and we report the role scaffold relative density play S in directing tenocyte bioactivity. Scaffold permeability and mechanical properties, both in tension and compression, were significantly influenced by relative density in a manner predicted by cellular solids models. Equine tenocytes showed greater levels of attachment, metabolic activity, soluble collagen synthesis, and alignment as well as less cell-mediated scaffold contraction in anisotropic CG scaffolds of increasing relative density. Notably, the lowest density scaffolds experienced significant cell-mediated contraction with associated decreases in tenocyte number as well as loss of microstructural integrity, aligned contact guidance cues, and preferential tenocyte orientation over a 14 day culture period. Gene expression analyses suggested tenocyte de-differentiation in the lowest density scaffold while indicating that the highest density scaffold supported significant increases in COMP (4-fold), tenascin-C (3-fold), and scleraxis (15-fold) expression as well as significant decreases in MMP-1 (9-fold) and MMP-13 (13-fold) expression on day 14. These results suggest that anisotropic scaffold relative density can help to modulate the maintenance of a more tendon-like microenvironment and aid long-term tenocyte transcriptomic stability. Overall, this work demonstrates that relative density is a critical scaffold parameter, not only for insuring mechanical competence, but also for directing cell transcriptomic stability and behavior. (C) 2011 Elsevier Ltd. All rights reserved.
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