A mechanism for effective cell-seeding in rigid,microporous substrates |
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Authors: | SJ Polak LE Rustom GM Genin M Talcott AJ Wagoner Johnson |
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Institution: | 1. Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 West Springfield Avenue, Urbana, IL 61801, USA;2. Department of Mechanical Engineering and Materials Science, Washington University School of Medicine, St. Louis, MO 60613, USA;3. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 60613, USA;4. Division of Comparative Medicine, Washington University School of Medicine, 660 S. Euclid Ave., Box 8061, St. Louis, MO 60613, USA;5. Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 W. Green St., Urbana, IL 61801, USA |
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Abstract: | Seeding cells into porous ceramic substrates has been shown to improve outcomes in surgical repair of large bone defects, but the physics underlying cellular ingress into such scaffolds remains elusive. This paper demonstrates capillary forces as a novel, yet simple, self-loading or self-seeding mechanism for rigid, microporous substrates. Capillary forces were found to draw cells through a microporous network with interconnections smaller than the diameter of the cells in suspension. Work here emphasizes CaP-based bone scaffolds containing both macroporosity (>100 μm) and microporosity (5–50 μm); these have been shown to improve bone formation in vivo as compared to their macroporous counterparts and also performed better than microporous scaffolds containing BMP-2 by some measures of bone regeneration. We hypothesize that capillary force driven self-seeding in both macro- and micropores may underlie this improvement, and present a mathematical model and experiments that support this hypothesis. The cell localization and penetration depth within these two-dimensional substrates in vitro depends upon both the cell type (size and stiffness) and the capillary forces generated by the microstructure. Additional experiments showing that cell penetration depth in vitro depends on cell size and stiffness suggest that microporosity could be tailored to optimize cell infiltration in a cell-specific way. Endogenous cells are also drawn into the microporous network in vivo. Results have important implications for design of scaffolds for the healing of large bone defects, and for controlled release of drugs in vivo. |
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Keywords: | Bone Porosity Cell seeding Scaffold Microstructure |
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