Reduced hydraulic permeability of three-dimensional collagen scaffolds attenuates gel contraction and promotes the growth and differentiation of mesenchymal stem cells |
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| Authors: | Vahid Serpooshan Marion Julien Oliver Nguyen Huifen Wang Ailian Li Naser Muja Janet E Henderson Showan N Nazhat |
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| Institution: | 1. Department of Mining and Materials Engineering, Faculty of Engineering, McGill University, 3610 University Street, Montreal, Quebec, Canada H3A 2B2;2. JTN Wong Laboratories for Bone Engineering, Faculty of Medicine, McGill University Health Centre, 740 Avenue Dr. Penfield, Montreal, Quebec, Canada H3A 1A4;1. School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou, 510640, China;2. Department of Mechanical Engineering, McGill University, Montreal, Quebec, H3A0C3, Canada;1. School of Engineering, University of British Columbia, 3333 University Way, Kelowna, BC V1V 1V7, Canada;2. Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), Department of Bioengineering, University of California – Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA;3. Department of Chemical and Biological Engineering, The University of British Columbia, 2360 East Mall, Vancouver, BC V6T 1Z3, Canada;4. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario M5S 3G8, Canada;1. Department of Mechanical Engineering & Materials Science, Washington University in St. Louis, St. Louis, MO, USA;2. Department of Physics, National Taiwan University, Taipei, Taiwan;3. Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA;4. ?Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran??;1. Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK;2. Division of Surgery and Interventional Science, University College London, London, UK;3. Tissue Repair and Engineering Centre, Institute of Orthopaedics, Division of Surgery and Interventional Science, UCL Stanmore Campus, Brockley Hill, London HA7 4LP, UK;1. Sport Innovation and Technology Center (SITC), Universiti Teknologi MalaysiaJ, Johor, Malaysia;2. Medical Device Technology Group, Faculty of Biomedical Engineering and Health Science, Universiti Teknologi Malaysia, Johor, Malaysia;3. Griffith School of Engineering, Griffith University, Australia |
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| Abstract: | Optimal scaffold characteristics are essential for the therapeutic application of engineered tissues. Hydraulic permeability (k) affects many properties of collagen gels, such as mechanical properties, cell–scaffold interactions within three dimensions (3D), oxygen flow and nutrient diffusion. However, the cellular response to 3D gel scaffolds of defined k values has not been investigated. In this study, unconfined plastic compression under increasing load was used to produce collagen gels with increasing solid volume fractions. The Happel model was used to calculate the resulting permeability values in order to study the interaction of k with gel mechanical properties and mesenchymal stem cell (MSC)-induced gel contraction, metabolism and differentiation in both non-osteogenic (basal medium) and osteogenic medium for up to 3 weeks. Collagen gels of fibrillar densities ranging from 0.3 to >4.1 wt.% gave corresponding k values that ranged from 1.00 to 0.03 μm2. Mechanical testing under compression showed that the collagen scaffold modulus increased with collagen fibrillar density and a decrease in k value. MSC-induced gel contraction decreased as a direct function of decreasing k value. Relative to osteogenic conditions, non-osteogenic MSC cultures exhibited a more than 2-fold increase in gel contraction. MSC metabolic activity increased similarly under both osteogenic and non-osteogenic culture conditions for all levels of plastic compression. Under osteogenic conditions MSC differentiation and mineralization, as indicated by alkaline phosphatase activity and von Kossa staining, respectively, increased in response to an elevation in collagen fibrillar density and decreased gel permeability. In this study, gel scaffolds with higher collagen fibrillar densities and corresponding lower k values provided a greater potential for MSC differentiation and appear most promising for bone grafting purposes. Thus, cell–scaffold interactions can be optimized by defining the 3D properties of collagen scaffolds through k adjustment. |
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