© 2005, The Society for Biotechnology, Japan
Bioreactor Design for Tissue Engineering
Ralf Pörtner,1* Stephanie Nagel-Heyer,1 Christiane Goepfert,1 Peter Adamietz,2 and Norbert M. Meenen3 Technische Universität Hamburg-Harburg, Bioprozess- und Bioverfahrenstechnik, Denickestr. 15, 21071 Hamburg, Germany,1 Universitätsklinikum Eppendorf, Institut für Biochemie und Molekularbiologie II, Martinistr. 52, 20246 Hamburg, Germany,2 and Universitätsklinikum Eppendorf, Unfall-, Hand- und Wiederherstellungschirurgie, Martinistr. 52, 20246 Hamburg, Germany3 Received 7 March 2005/Accepted 31 May 2005
Bioreactor systems play an important role in tissue engineering, as they enable reproducible and controlled changes in specific environmental factors. They can provide technical means to perform controlled studies aimed at understanding specific biological, chemical or physical effects. Furthermore, bioreactors allow for a safe and reproducible production of tissue constructs. For later clinical applications, the bioreactor system should be an advantageous method in terms of low contamination risk, ease of handling and scalability. To date the goals and expectations of bioreactor development have been fulfilled only to some extent, as bioreactor design in tissue engineering is very complex and still at an early stage of development. In this review we summarize important aspects for bioreactor design and provide an overview on existing concepts. The generation of three dimensional cartilage-carrier constructs is described to demonstrate how the properties of engineered tissues can be improved significantly by combining biological and engineering knowledge. In the future, a very intimate collaboration between engineers and biologists will lead to an increased fundamental understanding of complex issues that can have an impact on tissue formation in bioreactors. [Key words: tissue engineering, bioreactor, design considerations, cartilage]
The loss and damage of tissues cause serious health problems (1). In the US, almost one-half of the costs for medical treatments are spent on implant devices annually (2). Worldwide, 350 billion USD are expended for substitute of organs (3). The substitution of tissues (such as bone or cartilage) or joints with allograft materials includes the risk of infections by viruses (such as HIV, hepatitis C) or a graft rejection. Artificial implants such as those used in knee or hip replacement, have limitations due to their limited lifespan, insufficient bonding to the bone, and allergic reactions caused by material abrasion. New therapy concepts for practical medical applications are required. To this end, tissue engineered substitutes generated in vitro could open new strategies for the restoration of damaged tissues. The goal of tissue engineering can be defined as the development of cell-based substitutes to restore, maintain or improve tissue function. These substitutes should have organ-specific properties with respect to biochemical activity, microstructure, mechanical integrity and biostability (2). Cell-based concepts include the (i) direct transplantation of isolated cells, (ii) implantation of a bioactive scaffold for the stimulation of cell growth within the original tissue and (iii) implantation of a three di* Corresponding author. e-mail: email@example.com phone: +49-40-42878-2886 fax: +49-40-42878-2909 235
mensional (3D) biohybrid structure of a scaffold and cultured cells or tissue. Furthermore, non implantable tissue structures can be applied as external support devices (e.g., an extracorporal liver support when a compatible donor organ is not readily available [4, 5]) or engineered tissues can be used as in vitro physiological models for studying disease pathogenesis and developing new molecular therapeutics (e.g., drug screening [5, 6]). The generation of 3D tissue substitutes in...