INTEGRATION OF HOLLOW FIBER MEMBRANES IMPROVES NUTRIENT SUPPLY IN 3D TISSUE CONSTRUCTS

• Published in: International journal of artificial organs 2011-08, Vol.34 (8), p.645-645
• Main Authors: Stamatialis, D F, Bettahalli, NMS, Vicente, J, Moroni, L, Higuera, G A, Groen, N, Steg, H, Unadkat, H, de Boer, J, van Blitterswijk, CA, Wessling, M
• Format: Article
• Language: English
• ISSN: 0391-3988

Objectives: Despite the great progress in tissue engineering, development of clinically relevant size tissues with complex architecture remains a great challenge mostly due to limitations of nutrient and oxygen delivery to the cells. This study focuses on the development and utilization of a new perfusion culture system using hollow fiber membranes to provide adequate nutrient delivery to the cells within large three-dimensional (3D) scaffolds. Methods: Three-dimensional scaffolds were created by (i) rolling pre-seeded electrospun sheets around porous hollow fiber (HF) membranes and (ii) by integration of HF within free form fabricated (FFF) scaffolds. The culture of pre-myoblast (C2C12) cells under static and dynamic conditions on these scaffolds was investigated in a dedicated bioreactor. In fact, dynamic medium perfusion occurred via the HF lumen and around the 3D scaffolds. Various parameters such as fiber transport properties, fiber positioning within a scaffold, and medium flow conditions were optimized. The scaffolds were analyzed using scanning electron microscopy (SEM), histology and DNA assay. Results: The hollow fibers act as additional source of nutrients and oxygen to the cells by providing medium through the porous walls in a controlled manner at low shear stress. The SEM analysis and histology shows clearly that only integration of fibers achieves homogenous cell distribution within the scaffolds whereas the total DNA assay shows quantitatively high cell proliferation within the scaffolds. In the case of the electrospun multilayer scaffolds, cell migration occurs within the construct (shown using pre-labeled C2C12 cells) illustrating the potential of using our concept for developing more complex tissues. Conclusions: This study demonstrated the proof of concept of using polymeric hollow fibers as artificial capillaries for nutrient delivery to rather large 3D tissue constructs and could provide a basis for a new culture methodology for developing such constructs.