There is a strong scientific and clinical need for advanced in vivo simulation systems (IVSS, e.g., bioreactors) that support the maintenance of various tissue types in vitro in order to study disease pathogenesis in vitro, The goal of this proposal is to develop a bioreactor system that better approximates physiological environments while utilizing advances in non-destructive biomedical imaging techniques to study the structure and function of engineered or native tissues. The outcome of this work will be an instrumentation system to study the effects of environmental factors on tissue development and tissue disease states. The novelty of the system is in the non-destructive assessment capabilities combined with advanced controllable close-loop mechanical, biochemical and fluidic control systems to better mimic physiological conditions. Recent advances by the team involved in this proposal in bioreactor systems design have contributed to the combination of dynamic multi-dimensional mechanical stimulation with precise and accurate control over the biochemical and fluidic environments for ligament tissue engineering. Combining this expertise with noninvasive imaging techniques (microscopy, NMR) offers a unique opportunity to determine many important bioengineering parameters in situ. The objective of Phase I (R21) is to demonstrate proof-of-principle for a new reactor vessel design that supports the growth and development of ligament tissue (as an exemplary model based on our preliminary studies) while interfacing non-destructive imaging systems (e.g., microscopy and MRI). Phase II (R33) will seek to expand the reactor vessel design to support the growth and study of additional disc-like tissue types such as bone plugs. In parallel, modular reactor vessel cartridges and advanced IVSS close-loop mechanical, biochemical and fluidic control systems will be designed and developed while continually ensuring the reactor vessel is able to interface the selected imaging systems. An interdisciplinary team of investigators from Tufts University, Harvard University, MIT and Massachusetts General Hospital have combined their expertise to address the complexities of this topic, many of whom have longstanding collaborations in tissue engineering and bioreactor designs.
