Dan Simionescu, Ph.D.
Assistant Professor of Bioengineering
B.S. Biochemistry, 1981 University of Bucharest, Romania
Pre-doctoral Fellowship, 1987 & 1990 University of Pennsylvania
Ph.D. Biology (Magna cum laude), 1999 Institute of
Cellular Biology and Pathology, Bucharest, Romania
Postdoctorate Bioengineering, 2001 Clemson University
Pre-doctoral Fellowship, 1987 & 1990 University of Pennsylvania
Ph.D. Biology (Magna cum laude), 1999 Institute of
Cellular Biology and Pathology, Bucharest, Romania
Postdoctorate Bioengineering, 2001 Clemson University
Research Interests
Biomaterial Compatibility
Cellular and Molecular Cardiovascular Pathology
Minimally Invasive Therapies and Gene Manipulation
Patient-Tailored Regenerative Medicine
Cellular and Molecular Cardiovascular Pathology
Minimally Invasive Therapies and Gene Manipulation
Patient-Tailored Regenerative Medicine
Email:
Office: 501-1 Rhodes Research Center
Phone: 864.656.5559
Office: 501-1 Rhodes Research Center
Phone: 864.656.5559
Honors, Awards, and Professional Activities
Academy Award in Biological Sciences for “Research on Collagenous Biomaterials”, Romanian Academy, Bucharest, Romania. 1995Dr. Constantin Velican Award for “Research in atherosclerosis and cardiovascular diseases”, Bucharest, Romania. 1996 Society Memberships:
International Society for Applied Cardiovascular BiologyEuropean Cell Biology Organization Reviewer for Professional Journals:
BiomaterialsArteriosclerosis Thrombosis and Vascular BiologyActa BiomaterialiaMedical Sciences MonitorJournal of Biomedical Material ResearchCurrent Research
The long-term goal of my laboratory is to provide viable solutions to treatment of degenerative diseases, specifically focusing on the cardiovascular system. Two short-term goals fuel our excitement: 1) Biocompatibility: understanding the basics of biocompatibility at the molecular level and development of advanced, compatible biomaterials to be used in tissue repair or as replacement artificial tissues and organs, and 2) Regenerative Therapies : scaffold-based bio engineering approaches for regeneration of diseased tissues.
To reach this goal, during my career I combined input from the clinical setting (surgery, animal models of human diseases) and from basic biomedical knowledge (biochemistry, cell biology, transplant immunology) with engineering principles (design and construction of medical devices, biomechanics, fatigue testing, tissue engineering) in such a way as to improve performances of currently available medical devices as well as to develop novel regenerative treatments for cardiovascular diseases.
Cardiovascular disorders include diseases of the heart muscle (ischemia, fibrosis), heart valves, and blood vessels (degeneration and calcification, atherosclerosis, arteriosclerosis, aneurysms). Clinical consequences of these diseases include impairment of blood distribution and limited supply of oxygen and nutrients to essential organs such as the brain, lungs, liver, kidney, and the heart. In order to develop effective treatments, we focus on understanding cellular and molecular mechanisms of cardiovascular pathological scenarios.
For a majority of cardiovascular diseases there is no pharmacologic drug therapy available and the only alternative is to surgically replace diseased tissues with artificial devices. These include synthetic and tissue-derived biomaterials shaped in the form of heart valves for treatment of valve diseases, patches and occluders for treatment of septal defects, and tubular grafts for arterial and venous occlusions. These non-living devices restore the required function but fail in the long term due to poor biological integration leading to thrombosis, degeneration, and calcification.
To reach this goal, during my career I combined input from the clinical setting (surgery, animal models of human diseases) and from basic biomedical knowledge (biochemistry, cell biology, transplant immunology) with engineering principles (design and construction of medical devices, biomechanics, fatigue testing, tissue engineering) in such a way as to improve performances of currently available medical devices as well as to develop novel regenerative treatments for cardiovascular diseases.
Cardiovascular disorders include diseases of the heart muscle (ischemia, fibrosis), heart valves, and blood vessels (degeneration and calcification, atherosclerosis, arteriosclerosis, aneurysms). Clinical consequences of these diseases include impairment of blood distribution and limited supply of oxygen and nutrients to essential organs such as the brain, lungs, liver, kidney, and the heart. In order to develop effective treatments, we focus on understanding cellular and molecular mechanisms of cardiovascular pathological scenarios.
For a majority of cardiovascular diseases there is no pharmacologic drug therapy available and the only alternative is to surgically replace diseased tissues with artificial devices. These include synthetic and tissue-derived biomaterials shaped in the form of heart valves for treatment of valve diseases, patches and occluders for treatment of septal defects, and tubular grafts for arterial and venous occlusions. These non-living devices restore the required function but fail in the long term due to poor biological integration leading to thrombosis, degeneration, and calcification.
Biomaterial Compatibility
The fate of clinically implanted devices and biomaterials mainly depends on their biocompatibility. This area of research includes study of host reactions such as bio-recognition and immunological tolerance and the role of implant properties such as design, motion, mechanics, porosity, material surface properties, surgical techniques, and toxicity. In collaboration with scientists in Canada, we are studying the basic structural and functional properties of human heart valves in relation to their pathology, regeneration potential, and replacement. Ongoing studies in collaboration with Clemson faculty focus on reducing biomaterial degeneration by enhanced tissue stabilization with phenolic tannins. In collaboration with scientists at the University of Patras, Greece, we are developing tissue-derived biomaterials enriched with selected extracellular matrix components that protect tissues from degeneration and calcification upon implantation.
Minimally Invasive Therapies for Cardiovascular Pathology
For clinical situations of moderate severity, we strive to develop targeted local therapies. Ongoing work in collaboration with faculty at Clemson University aims at limitation of vascular degeneration and progression of aortic aneurysms by local delivery of phenolic tannins, agents that target extracellular matrix stabilization. Additional projects include targeted drug therapy for reduction of cardiac fibrosis by delivery of selected anti-fibrotic agents and gene manipulation (silencing and/or over expression). Ongoing research in collaboration with faculty at Clemson also attempts to limit vascular calcification by stem cell-derived therapy using local delivery of bone-resorbing cells, i.e. osteoclasts.
Regenerative Medicine for Pediatric & Adult Patients
In clinical situations where severe tissue degeneration occurs and major surgery is unavoidable, we endeavor to develop tissue-engineering approaches that will allow complete tissue regeneration and growth. These properties are especially important for use in children, who tend to rapidly outgrow their implants. Applications include myocardial patches to treat septal defects and to replace fibrosed myocardial segments, replacement heart valves and vascular grafts. In collaboration with scientists at Clemson, Medical College of Georgia and the National Cardiovascular Center in Osaka, Japan, we are developing tissue-engineering scaffolds from decellularized blood vessels and are studying their usefulness for cardiovascular applications in animal models. Scaffolds are treated with agents to control their in vivo biodegradability and enriched with specific growth factors to promote host cell infiltration, remodeling and revascularization. This exciting field is still under development but offers a unique potential to create functional and viable tissue constructs for patients requiring organ replacement.
Patient-Tailored Tissue Engineering
Surgeons use artificial devices in a “pathologic” environment, i.e. in patients affected by rheumatic and autoimmune diseases, diabetes, obesity, hypertension, and hypercholesterolemia. These patients exhibit altered immune and inflammatory responses, increased mechanical stress on cardiovascular structures and significantly altered blood chemistry. As a promise of the near future, it is also expected that prosthetic devices will be replaced by implantable tissue engineering constructs.
The biocompatibility of implantable devices and constructs in compromised patients is unknown. Moreover, there have been reports in the literature showing that implanted biomaterials fail more rapidly after implantation in patients suffering from diabetes and high cholesterol.
Currently, preclinical testing of devices involves their implantation and evaluation in “healthy” animals. While this approach may be convenient for screening purposes, it is of utmost importance to investigate behaviour of biomaterials and constructs in animal models of human diseases, relevant to their intended applications. Ongoing research in our laboratory is focused on defining biocompatibility of implanted biomaterials and scaffolds in animal models of human diseases. “Traditional” biomaterials and tissue-engineered scaffolds are implanted in experimental animals in which diabetes, obesity and hypercholesterolemia was induced and in control, healthy animals, and host reactions to implants are being evaluated and compared. This approach will provide a wealth of information on mechanisms of biomaterial pathology and will supply clues for their improvements.
The biocompatibility of implantable devices and constructs in compromised patients is unknown. Moreover, there have been reports in the literature showing that implanted biomaterials fail more rapidly after implantation in patients suffering from diabetes and high cholesterol.
Currently, preclinical testing of devices involves their implantation and evaluation in “healthy” animals. While this approach may be convenient for screening purposes, it is of utmost importance to investigate behaviour of biomaterials and constructs in animal models of human diseases, relevant to their intended applications. Ongoing research in our laboratory is focused on defining biocompatibility of implanted biomaterials and scaffolds in animal models of human diseases. “Traditional” biomaterials and tissue-engineered scaffolds are implanted in experimental animals in which diabetes, obesity and hypercholesterolemia was induced and in control, healthy animals, and host reactions to implants are being evaluated and compared. This approach will provide a wealth of information on mechanisms of biomaterial pathology and will supply clues for their improvements.
Recent Publications
Simpson CL, Lindley S, Eisenberg C, Basalyga DM, Starcher BC, Simionescu D, Vyavahare NR. “Toward cell therapy for vascular calcification: osteoclast-mediated demineralization of calcified elastin”. Cardiovascular Pathology, 2007.16:29-37.
Simionescu D. "Artificial heart valves". Wiley’s Encyclopedia of Biomedical Engineering, Metin Akay, editor. John Wiley and Sons, Inc., Hoboken, NJ. 2006.
Isenburg JC, Karamchandani NV, Simionescu D, Vyavahare NR. “Structural requirements for stabilization of vascular elastin by polyphenolic tannins”. Biomaterials, 2006.27:3645-51.
Simionescu D, Lu Q, Song Y, Lee JS, Rosenbalm TN, Kelley C, Vyavahare NR. “Biocompatibility and remodeling potential of pure arterial elastin and collagen scaffolds”. Biomaterials, 2006.27:702-13.
Simionescu D. “Prevention of calcification in bioprosthetic heart valves; challenges and perspectives”. Expert Opinions in Biological Therapy. 2004.4:1971-1985.
