BIOCOMPATIBILITY AND TISSUE REGENERATION LABORATORY

Research Facilities
The Biocompatibility and Tissue Regeneration Laboratory (BTRL), formed in 2006, is situated in the Rhodes Research Center, Department of Bioengineering at Clemson University. The facility occupies about 900 square feet and is split into two labs: Rhodes 507, which focuses on basic research, cell biology, and biochemistry, and Rhodes 514, which focuses on bioreactor development and biomechanical testing. The lab is equipped for sterile work with human stem cells and scaffolds and includes specific bioreactors, microscopes, and devices.

BTRL is equipped with all the necessary equipment for the proposed research. BTRL is equipped with CO2 incubators, sterile bio-hoods, and disposable plasticware for cell cultures and tissue engineering studies. For Enzyme-Linked Immunosorbent assay (ELISA) determinations of soluble proteins, we employ a high-tech 96-well plate ELISA reader and washer that greatly facilitates reproducible assays. Protein analysis is performed by acrylamide electrophoresis, western blotting and ELISAs, while PCR does gene expression. BTRL has access to fully equipped histology labs and the electron microscopy facility. Other laboratory equipment include refrigerated centrifuges reaching speeds of up to 12000 rpm that handle small volumes (1-2 ml) and refrigerated centrifuges that reach 5000 rpm for larger volumes (up to 50 ml tubes). We also use pipettors, both manual (Eppendorf) and digital (BrandTech), including multichannel pipettors. We use digital water baths, dry digital hybridization ovens for temperature-controlled reactions, etc. Other equipment includes balances, digital pH meters, hot plates and magnetic stirrers, homogenizers, and inverted microscopes with digital cameras for cell cultures and conventional histology.

Specialized equipment
Designed and built in our labs: the Heart Valve Bioreactors, Heart Valve Mini-Tester, the Vascular Bioreactor, and set up for compliance testing and burst pressure analysis of vascular grafts. These bioreactors are now available commercially from Aptus Bioreactors LLC.

Research Areas
Biomaterial Compatibility
The fate of clinically implanted devices and biomaterials mainly depends on their biocompatibility. This area of research includes the 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. We are studying human heart valves' basic structural and functional properties and their pathology, regeneration potential, and replacement. Ongoing studies focus on reducing biomaterial degeneration by enhanced tissue stabilization with phenolic tannins.

Minimally Invasive Therapies
For clinical situations of moderate severity, we strive to develop targeted local therapies. Ongoing work aims to limit vascular degeneration and progression of aortic aneurysms by local delivery of phenolic tannins, which target extracellular matrix stabilization. This patented technology is now in clinical trials. Additional projects include treatment of intervertebral disc degeneration, targeted drug therapy for reduction of cardiac fibrosis by delivery of selected anti-fibrotic agents and minimally invasive treatment of valve and myocardial diseases.

Regenerative Medicine for Pediatric and Adult Patients
The pinnacle of biomedical technologies for patient treatments are materials that can be implanted into a patient and remodeled into the patient’s native tissue over time. This is the epitome of tissue engineering, a discipline of regenerative medicine and the overall goal behind the research conducted in the BTRL. We endeavor to develop tissue-engineering approaches that allow complete tissue regeneration and growth in clinical situations where severe tissue degeneration occurs and major surgery is unavoidable.

These properties are especially important for children, who rapidly outgrow their implants. Applications include myocardial patches to treat defects and to replace fibrosed myocardial segments, replacement heart valves and vascular grafts, as well as novel scaffolds for regeneration of intervertebral discs. In collaboration with scientists at Clemson, the National Cardiovascular Center in Osaka, Japan, and the Cardiovascular Surgery Center in Cape Town, South Africa, 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 developing but offers a unique potential to create functional and viable tissue constructs for patients requiring organ replacement.

Translational Research; “From Bench to Bedside”
The definition of bench-to-bedside is: "Research undertaken in response to a defined clinical need which is directly applied towards the detection, prevention, and/or treatment of pathological, degenerative, or traumatic conditions, resulting in improved clinical outcomes for target patient populations."

The future of medicine depends on our ability to translate research done in the lab to an actual clinical scenario. The best example is that of pharmaceuticals we use daily: a drug is first envisioned, then developed in the lab, tested on animals, and finally tested in small groups of patients before being approved for patient use. Scaffolds and implants must undergo the same process for tissue engineering and regenerative medicine. While ample research has been done in the lab and on animals, few examples are known where regenerative medicine has been implemented clinically.

BTRL proposes to be at the forefront of translational regenerative medicine by interfacing the research facilities at Clemson University with the clinical collaborators at Greenville PRISMA Health and other clinics in the US. The main focus will be using autologous adult stem cells and scaffolds for tissue regeneration. This unique interface will facilitate “bridging the gap” between bench and bedside, working together with clinicians to understand the clinical needs and develop proposals for grant applications and clinical studies. We have several notable collaborations within the Greenville Hospital System but are continuously seeking clinical collaborators interested in this endeavor.