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Bioengineered organs not so far away by Heather Woolwine Public Relations Imagine a world where physicians order custom made organs and tissue for patient procedures; a world where health care and engineering become so intertwined, it’s difficult to tell where one discipline begins and another ends because the two mesh so well together. For those involved with the MUSC Bioengineering Program, this world is not so far away thanks to new research space at the Children’s Research Institute and a committed relationship with Clemson University’s well-known school of engineering. “It not only makes sense to work together because it’s cost efficient, but also because Clemson needs a close association with the medical center and we don’t have a bioengineering department,” said Dan Knapp, Ph.D., MUSC Clemson-MUSC bioengineering program director and professor of Pharmacology. “Historically, Clemson has placed an emphasis on biomaterials like replacement joints and are now moving towards living tissue. The key theme in our collaborative effort is tissue engineering.” “Bioengineering is one key research field that promotes the fast translation of fundamental biology and engineering discoveries, design and development into  real clinical scenarios,” said Xuejen Wen, M.D., Ph.D., MUSC Bioengineering. “We are fortunate to work in the new CRI building. The research facilities are top notch and certainly serve as major incentive for conducting quality research,” said Anand Ramamurthi, Ph.D., MUSC Bioengineering.  “The concept of open lab spaces is a first here, but as we are learning more each day, a very cleverly planned move to encourage us to interact and exchange science and research resources with our basic science/clinical neighbors.” Some on campus may remember a story in the local press and The Catalyst about a year ago that detailed the work by Clemson engineer Thomas Boland, Roger Markwald, MUSC Cell Biology and Anatomy,  and  Vladimir Mironov’s, MUSC Cell Biology and Anatomy, program concerning a converted inkjet printer that could print living tissue. “Some of our future products could be artificial blood vessels or new neural tissue for those affected by spinal cord injuries,” Knapp said. Under the chairmanship of Martine LaBerge, Clemson Bioengineering Department, Ramamurthi and Wen serve as the primary bioengineering faculty for the 12 Clemson graduate students who take courses via video conferencing in addition to classes here to earn a Ph.D. in engineering. Currently recruiting more senior level faculty, the program has more than a dozen MUSC faculty serving as adjunct professors and has several million dollars in pending grant applications.  Ramamurthi’s research interests lie in the areas of cardiac and vascular tissue engineering, with a particular emphasis on the development and characterization of extracellular matrix (ECM)-derived biomaterials as scaffolds to modulate vascular regeneration or repair. The primary long-term research objective is to develop new tissue engineered grafts and to prevent re-occlusion and loss of patency of small diameter blood vessels and vascular grafts following surgical intervention.  Two of the important questions Ramamurthi seeks to answer are whether these biomaterials will interact with cells as cell culture scaffolds and how they can be tailored to evoke cell responses that more closely resemble healthy native cells rather than the often exaggerated natural repair mechanisms that follow vascular injury.  “Two research projects best showcase our research activities,” Ramamurthi said. “The first seeks to develop cell scaffolds tailored to induce cultured cells that generate elastic matrix structures used to restore vessel elasticity and inhibit SMC hyperplasia at sites of vascular aneurysms where irreversible elastin degradation occurs. Research in our lab has shown that hylans are capable of inducing prolific synthesis of an elastin matrix closely resembling the native elastin ultrastructure. We are currently striving to improve the quality of this matrix by designing composite hyaluronan scaffolds based on a mixture of native long-chain and fragmented hyaluronan, which can evoke very different biologic responses.”  Most vascular grafts tend to perform poorly because they fail to spontaneously regenerate a surface layer of protective endothelial cells. Although this problem can be overcome, it requires invasive repeat surgeries and large amounts of healthy tissue that’s not always available.  “To address this, we have recently initiated a research project to explore umbilical cord blood progenitor (stem) cells, available readily and non-invasively, as a source of expandable healthy endothelial cells for vascular graft seeding,” Ramamurthi said. Wen conducts a number of projects for the program, including: Plasticity of umbilical cord blood stem cells in multiple tissues and organs, such as the brain, heart, pancreas, and kidney. Tissue engineering for spinal cord repair: By engineering a controlled environment at the lesion site, neuronal bridging devices promote injured CNS neurons to regenerate axons, guide their regeneration to appropriate targets, and recover functions. Tissue engineering to treat neurodegenerative diseases: A novel space creation concept which could be combined with a tissue engineering strategy to seed stem cells and to treat diseases such as Parkinson’s, Alzheimer’s and Huntington’s diseases. Bone and muscle tissue engineering: Several types of novel  biodegradable scaffolds were developed for engineering bone and muscle tissue that mimics the  macro- and micro-structure of natural tissues. Cardiac tissue engineering: The ultimate goal of the proposed study is to develop stem cell therapies to facilitate cardiac tissue repair based on the principles of tissue engineering and regenerative medicine. Sensory system prevention and restoration: The application of  tissue engineering techniques for vision and hearing restoration. Drug delivery: Three types of drug delivery system are in development, including selective-permeable hollow fiber membranes, microspheres, and nano-gel/nano-particles. Nanostructured biomaterials: Coatings of nano-scale thickness biocompatible films for medical applications are in development, such as scaffold for tissue engineering, biosensor/bioprobe, and drug delivery. A future area of development for the program lies with the recent funding of two lottery endowed chairs for a proteomics center that would serve to develop new technologies and overlap with the current bioengineering program.  The center would construct and analyze microfluetic devices for proteomic analysis.  For more information on the MUSC Bioengineering program, go to http://www.musc.edu/bioengineering. Why is bioengineering so important to the future of the health care community?  “Traditionally viewed as a biologic entity, the human system is increasingly recognized as a ‘biologic reactor’ within which the basic precepts of engineering, phenomena transport, fluid dynamics, kinetics, or mechanics among others, are perfectly valid. Thus it is no surprise that bioengineers have increasingly come to collaborate with basic scientists and clinicians to develop effective and comprehensive solutions to overcome the out-standing clinical challenges that face us today. Bioengineers today play key roles in developing the tools for disease diagnosis, designing prosthetic devices and artificial organs, and improving surgical equipment to better serve the surgeon and benefit the patient. In fact, the net importance of bioengineering in health care can be gauged by the fact that the medical devices industry in the US today accounts for nearly $75 billion in annual revenues. In my perspective, we are barely at the tip of the iceberg; the bioengineering field is rapidly maturing and its future impact on disease diagnosis in improving quality of life for patients is likely to be tremendous.” —Anand Ramamurthi, Ph.D., MUSC Bioengineering   Friday, Feb. 18, 2005 Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. 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