Center for Technology & Engineering, Harvard Medical School
Benchtop Bioreactor for growth of Anterior Cruciate Ligament tissue

David Kaplan, Ph.D., Biomedical Engineering Department – Tufts University
Greg Altman, Ph.D., Biomedical Engineering Department – Tufts University
Peter Stark
Dale Larson, Director, Center for Technology & Engineering - Harvard Medical School

A novel bioreactor system will be developed that can provide a broad range of environmental stimuli for tissue engineering studies. The goal of the project is to provide the tissue-engineer with an improved reactor system to be better able to understand the effects of perfusion, gas transport, mechanical forces, and biochemical stimuli on cell and tissue differentiation and development in vitro. This advance is critical if tissues engineered in vitro are to be attained that better duplicate tissue structure and function in vivo. Furthermore, the proposed reactor will reduce the need to develop tissue-specific reactors as is currently the mode in the field today. This advanced reactor system will build upon an initial bioreactor design developed to permit the application of complex multi-dimensional strain to cells growing on matrices in the reactor. This system was used to induce differentiation of adult stems cells via multi-dimensional cyclic strain into ligament forming cells, without the need for exogenous cell signaling factors; a major advance in the field. We plan to build upon this initial success by enhancing the bioreactor to broaden its utility for these types of studies. The proposed system will be expanded to provide multi-dimensional load-control, process control, and fluidic and reagent handling systems to explore developmental cascades for a variety of tissues including ligaments, tendons, arteries, muscle, bone, cartilage, and nerves, as well as fundamental studies of cellular and tissue responses.

Key new features of this bioreactor will be:

1. control of stress and strain (force and displacement) during tissue growth;
2. monitoring and control of key process variables during growth of tissue;
3. automated fluidics system to provide the capability of adding reagents, adding and removing growth medium, and collecting samples of the growth medium as it exits the tissue;
4. Windows interface executed under software control.

This bioreactor will offer researchers the ability to develop an improved understanding of the science of tissue engineering by providing them with a programmable instrument with a broader range of environmentally-relevant features to mimic the in vivo environment. The system has the potential to become a platform used widely in the field of tissue engineering thereby accelerating progress in the field.