Development of a dynamic bioreactor system for orthopaedic tissue engineering applications.

摘要

Bone voids caused by physical trauma or surgery result in excess of 500,000 surgical bone graft procedures annually. Bone filler materials, used to expedite the healing process, currently include autografts, demineralized bone, and a limited selection of synthetic implant materials. Limitations in available autograft donor material, donor site morbidity and physiological response to acellular materials expound the need for cell-based tissue-engineered graft alternatives. Orthopaedic tissue engineering is seeking to provide these alternative treatments through the combined use of novel bioreactor technology, three-dimensional biomaterial scaffolds and multipotent cell sources derived from the patient.; An innovative bioreactor design has been developed to accommodate the in vitro culture requirements necessary to accurately model the in vivo conditions found in normal bone. Research progression stems from the preliminary design to experimental aims of increasing complexity as characterized by the following themes and objectives: (1) Bioreactor design and preliminary dynamic experiments. (2) Characterization of temporal cell-material interactions under static conditions to evaluate potential biomaterials for use in future dynamic bioreactor experiments. (3) Cell response to interactive perfusion and hydrostatic stimuli to effectively demonstrate the full bioreactor potential in modeling the in vivo environment. (4) Co-culture configuration for cultivating an osteochondral plug as a demonstration of the inherent flexible nature of the modular bioreactor design.; The bioreactor design underwent an evolution as manual components and limiting physical factors were replaced with computer controlled automation and advanced solutions for optimal three-dimensional cell culture. Preliminary experiments provided refinement in experimental protocols, techniques and endpoint assays. Early studies provided a steep learning curve in bioreactor application and favorable design modifications. In the end, the bioreactor system became a valuable tool in the development and evaluation of three-dimensional tissue-engineered cellular constructs for potential orthopaedic applications.