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Tissue Engineering

Principal Investigator:
Joseph P. Vacanti, M.D.

The Tissue Engineering and Organ Fabrication Laboratory on Wellman 6 is newly renovated. The laboratory is funded by the NIH, the DoD through CIMIT, and corporations interested in tissue engineering. Residents and fellows have been successful in competition for national scholarships and are encouraged to present their research at national meetings and publish their data in high impact journals.

Our laboratory has been designing and fabricating organs and tissues for over 17 years. We have worked closely with scientists and engineers at MIT and have studied approximately 30 different tissues of the body. We have 50 patents or patents pending for the field. We use cells combined with special plastics which act as the scaffolding upon which the living tissue is built. Living skin, cartilage, bone, and blood vessels are now in human use.

Our laboratory here works closely with engineers and scientists from MIT and the Draper Laboratories. Collaborating with Professor Robert Langer from MIT, we began building living tissues using living cells on specially designed degradable plastics. This invention is now patented and being tested worldwide.

Much of the research that the Tissue Engineering and Organ Fabrication Laboratory is involved with focuses on improving methods of transplantation for diseased bodily organs. The organ donor shortage has become a severe problem as transplant waiting lists become increasing longer and patients have to wait longer for their new organs. In response to this problem, the lab is investigating the role of tissue engineering in creating an improved or alternative method of organ transplantation.

Current research projects include:

Organ Replacement
While transplantation has been the established treatment for end-stage liver disease, the shortage of donor organs continues to become more severe over time. For this reason our laboratory has investigated tissue engineering of the liver using cell-laden polymer devices as a means of generating new tissue replacements. A small number of healthy hepatocytes (liver cells) are harvested, cultured in vitro until they develop new tissue formation, and seeded onto a biodegradable polymer which serves as a structural scaffold upon which the cells can grow. The idea is that, once implanted back into the patient, the scaffold will degrade leaving behind a durable tissue structure that can provide a long-term solution for specific ailments by recreating the essential functions of the organ. Currently we are designing systems with their own blood supply using silicon micromachining technology. We are now also working on kidney, lung, and heart tissue.

Cardiovascular Tissues
Diseases of the cardiovascular system remain the leading cause of morbidity and mortality worldwide. Approximately 57 million North American people suffer from one or more forms of cardiovascular disease and the cost of treatment exceeds $260 billion. Cardiovascular tissue engineering focuses on the development of the blood vessels, heart valves and heart muscle.

a) Blood Vessels:
The majority of patients with vascular atherosclerotic diseases need blood vessel substitutes to reestablish vascular continuity. The ideal blood vessel should be a compliant, functioning substitute with the ability to repair, remodel, and grow. The internal surface should be covered with an intact and functioning endothelial cell lining to prevent thrombosis.

b) Heart Valves:
Approximately 300,000 procedures for repair or replacement heart valves are performed annually worldwide. Over 95% of these operations affect valves in the systemic circulation. The current available prosthetic heart valves have excellent long-term function but need life long anticoagulation to prevent clotting and are also susceptible to infections. The alternatively used bioprostheses (porcine valves or bovine pericardium) provide better fliud dynamics and avoid anti-coagulation. However, these valves have limited durability. None of the current valve devices provide growth potential. The tissue engineering of heart valves focuses on the development of a healthy living heart valve.

c) Myocardium:
Heart transplantation is the only established therapy for end-stage heart failure; however, the shortage of donor organs has become a major limitation. The transplantation waiting lists world wide are increasing in numbers and patients have to wait for increasingly longer periods of time. For this reason there has been great interest in cell transplantation as an alternative to heart transplantation. Using the principles of tissue engineering, we are currently investigating cardiomyocyte transplantation with polymers to generate new tissue replacement. The purpose of our studies is to investigate the effects of different polymers on the function and survival of injected cardiomyocytes in vitro and in vivo, to establish a method of injecting a critical mass of cardiomyocytes to improve heart function.

Neural Regeneration
We currently are exploring the use of neural stem cells combined with degradable scaffolds to repair spinal cord injury and peripheral nerve injury.

Intestinal Replacement
Many adults and children are afflicted with short gut syndrome and intestinal transplantation is the only hope for survival. We are generating lengths of functional intestine using spheroids of intestinal cells on tubes made of degradable polymers.

Structural Tissues
The structural tissues of cartilage and bone have advanced most quickly in this field and some are available for clinical use. We are focused on tissue engineered substitutes for craniofacial applications as well as hand and orthopedic applications.

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