Naren Vyavahare, Ph.D.
Hunter Endowed Chair and Prof. of Bioengineering
B.S. Chemistry, 1983 University of Pune, India
M.S. Organic Chemistry, 1985 University of Pune, India
Ph.D. Chemistry, 1991 University of Pune, India
Postdoctorate Chemistry, 1993 Rutgers University
M.S. Organic Chemistry, 1985 University of Pune, India
Ph.D. Chemistry, 1991 University of Pune, India
Postdoctorate Chemistry, 1993 Rutgers University
Research Interests
Cardiovascular Implants
Synthetic & Biopolymers as Biomaterials
Drug/ Gene Site Specific Delivery
Cell-ECM Interactions
Synthetic & Biopolymers as Biomaterials
Drug/ Gene Site Specific Delivery
Cell-ECM Interactions
Email:
Office: 401-4 Rhodes Research Center
Phone: 864.656.5558
Office: 401-4 Rhodes Research Center
Phone: 864.656.5558
Honors, Awards, and Professional Activities
coming soon Current Research
My research involves an application of chemistry, biochemistry, and engineering principles to the development of biomaterials. This includes primary syntheses of therapeutic polymers for biomaterial use and development of natural protein/tissue derived biomaterials as well as study of biomaterial-protein interactions with advance spectroscopic instruments.
Tissue-Derived Biomaterials, Tissue Engineering
Tissue-derived biomaterials are frequently used as xenotransplant materials in the heart valve and vascular prosthesis due to their excellent biocompatibility. The focus of my research over the last several years is to develop heart valves from porcine aortic valves. Calcification and degeneration are the major contributing factors for the failure of bioprosthetic heart valves (BPHV) derived from glutaraldehyde cross linked porcine aortic valves or bovine pericardium, valved human aortic homografts, autografts fabricated from dura mater and synthetic polymeric prostheses. I have demonstrated for the first time that ECM structural components, such as collagen and glycosaminoglycans (GAGs), present in the bioprosthetic heart valve have major roles in valvular degeneration and calcification. In particular, GAGs present in the spongiosa layer of BPHV are extremely important for mechanical properties. We have found that GAGs are not stabilized by the usual fixation methods and are lost from the xenograft heart valves causing loss of flexural rigidity. I am working on the strategies that would maintain structural integrity of tissue- derived biomaterials so that the useful life of these devices could be extended. This includes chemical modification of implants, use of alternative crosslinking strategies other than glutaraldehyde, attachment of anti-calcification drugs, site-specific drug delivery and gene therapy. As a next phase of this research, I would use porcine aortic valves for tissue engineered heart valve applications by derivatizing tissues in such a way as to favor cell ingrowth and extracellular matrix development.
Development of Synthetic Polymer Derived Biomaterial
Currently, I am working on the modification of polyurethane surfaces to make them more biocompatible and to allow cell attachment and growth for heart valves and wound-healing applications. The research involves chemical incorporation of biological signal molecules such as oligopeptides in the hydrogels, which would promote specific cellular responses while avoiding other unwanted cellular interactions. New peptide sequences for binding to cell adhesion molecules such as integrins are continuously being discovered so that these can be incorporated into biomaterials to achieve various responses of blocking, presenting and receiving biological information.
Site-Specific Therapy for the Treatment of Diseases: Biomaterials, Drug Delivery, Gene Therapy
The success of gene therapy, DNA and anti-sense oligonucleotide delivery for treating a variety of diseases will largely depend upon the site-specific delivery of these agents. My research focus is to develop biomaterials that will deliver these agents at the desired site. I am working on a hydrogel system, which can be used to deliver plasmid DNA, and adenovirus-containing desired DNA to the specific sites in applications such as wound healing, restenosis and calcification. Recent results in our laboratory have shown that such hydrogels could retain adenovirus (containing ?-galactosidase reporter gene). The adenovirus particles can be slowly released in active form either in cell cultures or in animal models (rabbit ear ischemic wound healing model and diabetic mouse would healing model) and transfect cells for several days. Similarly, pharmacological agents can be attached to the polymers (either natural agents such as collagen and glycosaminoglycans or synthetic agents such as acrylate/methacrylates) which will be released by biological trigger mechanisms such as higher local expression of certain enzymes.
ECM Structure and Signaling in Cardiovascular Calcification
My research also includes a study of cellular response to the extra cellular matrix with elastin as a model ECM protein. Elastin is a major ECM protein present in the aorta and arterial wall. Elastin undergoes calcification in disease processes such as atherosclerosis, bioprosthetic heart valve calcification and age-related arterial hardening. The mechanisms of elastin calcification are unknown and no therapy is available to prevent elastin calcification. I study the mechanisms of elastin calcification in animal models (rat subdermal and rat aortic allograft implants). Elastin undergoes similar pathophysiologic calcification in these animal models as seen in the pathologic disease processes. I hypothesize that injury or alteration of the native elastin structures leads to elastin calcification. I have localized high matrix metalloproteinases and tenascin-C (ECM glycoprotein involved in tissue remodeling) activity very close to the first calcific deposits on elastin. Moreover, I have shown that aluminum chloride pretreatment of elastin leads to irreversible binding of the aluminum ions to the elastin, altering the spatial structures of elastin so that it completely resists calcification. Thus, my research focus includes understanding the mechanisms (including the role of MMPs, tenascin-C and alkaline phosphatase) of elastin calcification and its prevention. To that effect, I study protein-protein interactions and conformational changes in the ECM protein structure caused by a variety of agents with spectroscopies, and relate the effects in terms of protein function in calcific diseases.
Recent Publications
Naren Vyavahare, “Preventing calcification of bioprosthetic heart valves: Are we there yet?”, Perspectives in Cardiac Surgery, 2(2), 5-12, 2005
J. Connolly, I. Alferiev, J. Clark-Gruel, N. Eidelman, M. Sacks, E. Palmatory, A. Kronsteiner, S. DeFelice, J. Xu, R. Ohri, N. Narulam, Naren Vyavahare, and Robert Levy, “ Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance”, American Journal of Pathology, 166:1-13, 2005.
D. Basalyga, D. Simionescu, W. Xiong, T. Baxter, B. Starcher, Naren Vyavahare, “Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases”, Circulation, 110(22):3480-7, 2004.
Q. Lu, K. Ganeshan, D. Simionescu, Naren Vyavahare, “Novel porous elastin and collagen scaffolds for tissue engineering”, Biomaterials 25 (22): 5227-5237, 2004.
Sun W, Sacks M, Fulchiero G, Lovekamp J, Vyavahare Naren, Scott M, “Response of heterograft heart valve biomaterials to moderate cyclic loading”, Journal of Biomedical Materials Research, PART A 69A (4): 658-669, 2004.
