CU-BioE: BTRL

Lab Coordinator: Dr. Dan Simionescu

Motto: “Regenerative Medicine through Interdisciplinary Translational Research”

HISTORY AND MISSION

BTRL was founded in August of 2006 with the overall mission to provide viable solutions to treatment of degenerative diseases, specifically focusing on the cardiovascular system. 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.

Two short-term goals fuel our excitement:

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.
Regenerative Therapies: scaffold-based bioengineering approaches for regeneration of diseased tissues. To reach this goal, we combine 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.

RESEARCH INTERESTS

1. Biomaterial Compatibility

Host reactions, bio-recognition and immunological tolerance.
Role of implant properties such as design, motion, mechanics, porosity, material surface properties, surgical techniques and toxicity.

2. Minimally Invasive Therapies for Cardiovascular Pathology

Limitation of vascular degeneration and progression of aortic aneurysms by local delivery of phenolic tannins, agents that target extracellular matrix stabilization.
Targeted drug therapy for reduction of cardiac fibrosis by delivery of selected anti-fibrotic agents and gene manipulation (silencing and/or over expression).
Limitation of vascular calcification by stem cell-derived therapy using local delivery of bone-resorbing cells, i.e. osteoclasts.

3. Regenerative Medicine for Pediatric & Adult Patients

Tissue-engineering approaches that will allow complete tissue regeneration and growth, properties especially important for use in children, who tend to rapidly outgrow their implants.
Myocardial patches to treat septal defects and to replace fibrosed myocardial segments
Tissue engineered replacement heart valves and vascular grafts.

4. Patient-Tailored Tissue Engineering

Defining biocompatibility of implanted biomaterials and scaffolds in animal models of human diseases such as diabetes, obesity and hypercholesterolemia.

GRANTS

INBRE – $150,000, five-year grant to study advanced technologies for matrix stabilization in artificial heart valves.
NIH R21 - $400,000, two-year grant for research on tissue-engineered vascular grafts used for replacement of diseased arteries. The "Clemson Bioactive Vascular Graft", based on novel chemically-engineered, cell-populated arterial scaffolds will be tested for functionality and biocompatibility in laboratory bioreactors and in animal models.

ABOUT BTRL

Room #507, Rhodes Research Center
Clemson University, Department of Bioengineering
Clemson, SC 29634-0905, USA
Phone: 864-656-2441
Contact Info: Betsy Tedder, PhD student and Lab Manager (mtedder@clemson.edu)

RESEARCH FACILITIES at the BTRL

BTRL is equipped with all necessary equipment for proposed research.

EQUIPMENT

For cell cultures and tissue engineering studies, BTRL is equipped with a CO2 incubator, sterile biohood, and disposable plasticware. Other laboratory equipment includes: a refrigerated centrifuge reaching speeds of up to 12000 rpm that handles small volumes (1-2 ml) and a refrigerated centrifuge that reaches 5000 rpm for larger volumes (up to 50 ml tubes). We also use two sets of pipettors: manual (Eppendorf) and digital (BrandTech), including mutichannel pipettors. For Enzyme-Linked Immunosorbent Assays (ELISA) determinations of soluble proteins we employ a high-tech 96-well plate ELISA washer that greatly facilitates reproducible assays. For temperature-controlled reactions, we use two digital water-baths and a dry digital hybridization oven. For cell cultures and conventional histology, we use an inverted Zeiss microscope with digital camera. Setup for compliance testing and burst pressure analysis of vascular grafts, bioreactor for heart valve tissue engineering (under development). Other equipment includes balances, digital pH meters, hot plates and magnetic stirrers, homogenizers, refrigerator and freezer (-20oC), etc.

PEOPLE: July 2007 (left to right)

Dr. Dan T. Simionescu, Dr. Agneta Simionescu, Jeremy Mercuir, Betsy Tedder, Tom Chuang, and Lee Sierad
group photo