Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs

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Bettahalli, N.M.S. and Vicente, J. and Moroni, L. and Higuera, G.A. and Blitterswijk, C.A. van and Wessling, M. and Stamatialis, D.F. (2011) Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs. Acta Biomaterialia, 7 (9). pp. 3312-3324. ISSN 1742-7061

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Abstract:Sufficient nutrient and oxygen transport is a potent modulator of cell proliferation in in vitro tissue-engineered constructs. The lack of oxygen and culture medium can create a potentially lethal environment and limit cellular metabolic activity and growth. Diffusion through scaffold and multi-cellular tissue typically limits transport in vitro, leading to potential hypoxic regions and reduction in the viable tissue thickness. For the in vitro generation of clinically relevant tissue-engineered grafts, current nutrient diffusion limitations should be addressed. Major approaches to overcoming these include culture with bioreactors, scaffolds with artificial microvasculature, oxygen carriers and pre-vascularization of the engineered tissues. This study focuses on the development and utilization of a new perfusion culture system to provide adequate nutrient delivery to cells within large three-dimensional (3D) scaffolds. Perfusion of oxygenated culture medium through porous hollow fiber (HF) integrated within 3D free form fabricated (FFF) scaffolds is proposed. Mouse pre-myoblast (C2C12) cells cultured on scaffolds of poly(ethylene-oxide-terephthalate)–poly(butylene-terephthalate) block copolymer (300PEOT55PBT45) integrated with porous HF membranes of modified poly(ether-sulfone) (mPES, Gambro GmbH) is used as a model system. Various parameters such as fiber transport properties, fiber spacing within a scaffold and medium flow conditions are optimized. The results show that four HF membranes integrated with the scaffold significantly improve the cell density and cell distribution. This study provides a basis for the development of a new HF perfusion culture methodology to overcome the limitations of nutrient diffusion in the culture of large 3D tissue constructs.
Item Type:Article
Copyright:© 2011 Elsevier
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Science and Technology (TNW)
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Link to this item:http://purl.utwente.nl/publications/80637
Official URL:http://dx.doi.org/10.1016/j.actbio.2011.06.012
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