The mission of the Ramamurthi lab is to develop novel tissue engineering solutions to regenerate cardiovascular tissues or modulate their response to injury or disease in neonatal, pediatric, and adult populations. The lab seeks to investigate tissue engineering methods and materials to be able to faithfully replicate the biocomplexity of vascular matrix assembly and thereby to regenerate architectural and functional mimics of cardiovascular tissues. Current projects include (1) biomolecular and biomaterial-based cues for biomimetic elastin synthesis, matrix assembly, and maturation; (2) cell sourcing for elastic matrix engineering: Diseased vascular cells and vascular progenitors; (3) cellular mechano-transduction to modulate patterns of elastic matrix deposition; (4) customized elastic matrix regenerative repair for aortic aneurysm regression; and (5) lycosaminoglycan-based therapeutic paradigms for vascular degeneration.
Abdominal aortic aneurysms (AAAs) are potentially fatal conditions afflicting major blood vessels, which are characterized by a loss of wall flexibility, and ultimate vessel weakening and rupture. This occurs due to breakdown and loss of rubber-like protein fibers (elastin) that normally help vessels to revert to their original shape and form after expanding to accommodate blood flow. Presently, it is possible to slow growth of AAAs by using drugs targeted at inhibiting enzymes that breakdown elastic fibers. However, because adult and diseased vascular cells cannot themselves produce much new elastin and are incapable of replicating the complex sequence of events involved in assembly of elastin precursors into fibers and other superstructures, which occurs during fetal development, it is not possible to repair already disrupted elastic matrix to reverse the AAA. This study proposes to provide cells in culture, and then within living AAA vessels, a combination of biological molecules and/or biomaterials that we have found to significantly increase elastin production by healthy and diseased vascular cells, and protect these newly generated elastic matrix structures from enzymatic breakdown. This strategy will significantly benefit the development of new, non-surgical treatment strategies that can reverse existing AAAs, which is not possible at present. Our technologies will also address the insufficiency of conventional tissue engineering techniques and materials to promote the generation of elastic matrix structures (e.g., fibers) within vascular tissue replacements engineered in the lab using patient-derived cells.
Venkataraman, L., and Ramamurthi A., Induced Elastin regeneration within 3–Dimensional Collagen Scaffolds. Tissue Eng Part A. 2011 Aug 29. [Epub ahead of print]
Bashur, C., and Ramamurthi, A., Aligned Electrospun Scaffolds and Elastogenic Factors for Vascular Cell-mediated Elastic Matrix Assembly. Accepted to Tissue Engineering and Regenerative Medicine, 2011.
Gacchina C.E., Deb P., and Ramamurthi A., Elastogenic Inductability of Smooth Muscle Cells from a Late-Stage Rat Model of Abdominal Aortic Aneurysms. Tissue Eng Part A. 2011 Jul;17(13-14):1699-711.
Gacchina C.E., Brothers, TE, and Ramamurthi A., Evaluating Smooth Muscle Cells from CaCl2-Induced Rat Aortal Expansions as a Surrogate Culture Model for Study of Elastogenic Induction of Human Aneurysmal Cells. Tissue Eng Part A. 2011 Aug;17(15-16):1945-58.