Our lab has a versatile experimental system for the ex-vivo biomechanical and functional testing of tubular tissues. This includes our novel work on the biomechanical characterization of the urethra, colon and esophagus in health, disease and regeneration. Our urethra work includes quantification of active contractile responses due to smooth and striated muscle, alterations of urethral biomechanical function following vaginal distension (a model for stress urinary incontinence due to childbirth), or induction of diabetes mellitus or spinal cord injury. Our esophagus work included the quantification of biomechanical properties over time for an extracellular matrix-based reconstructed esophagus.
1. Prantil-Baun R, de Groat WC, Miyazato M, Chancellor MB, Yoshirmura N, Vorp DA, “Ex VivoBiomechanical, Functional, and Immunohistochemical Alterations of Adrenergic Responses in the Female Urethra in a Rat Model of Birth Trauma,” Am J Physiol Renal Physiol 2010 Aug:299(2):F316-24, PMID: 20444739, PMCID: PMC2928526
2. Haworth DJ, Kitta T, Morelli B, Chew DW, Yoshimura N, de Groat WC, Vorp DA, “Strain-dependent urethral response”, Neurourology and Urodynamics, 2011 Nov;30(8):1652-8, PMID 21826722
Our lab has a long history of developing and utilizing novel ex-vivo vascular perfusion systems to measure biomechanical and functional properties of vascular segments under accurately simulated hemodynamic conditions. This includes the ability to assess the dynamic compliance and stiffness of veins and arteries under pulsatile pressure and flow, and bending/flexure, stretching and twisting (to simulate the coronary artery mechanical environment due to heart-induced deformations). My lab has also utilized these tools to assess the role of mechanical factors in coronary atherogenesis, intimal hyperplasia and vein graft thrombosis. We have coined the term “mechanopathobiology” to describe our approach in studying the association of mechanical factors in pathology.
1. El-Kurdi MS, Vipperman JS, Vorp DA, “Control of Circumferential Wall Stress and Luminal Shear Stress within Intact Vascular Segments Perfused Ex Vivo,” J Biomech Eng, 2008 Oct;130(5):051003-7, PMID: 19045510
2. VanEpps JS, Londono R, Nieponice A, Vorp DA, “Design and Validation of a System to Simulate Coronary Flexure Dynamics on Arterial Segments Perfused Ex Vivo,” Biomech Model Mechanobiol. 2009 Feb;8(1):57-66, PMID: 18297319 PMID: 18297319
3. VanEpps JS, Chew DW, Vorp DA, “Effects of Cyclic Flexure on Endothelial Permeability and Apoptosis in Arterial Segments Perfused Ex Vivo,” J Biomech Eng, 2009 Oct;131(10):101005, PMID: 19831475
Our lab has developed and patented technology that recently led to the formation of a start-up company (Neograft Technologies, Inc.) for which Dr. Vorp was awarded a University of Pittsburgh Innovator Award in 2009. This technology involves placing a biodegradable “wrap” to prevent the acute distension of vein grafts (much like “girdle”). Clinical trials of this technology are currently under way.
1. El-Kurdi MS, Hong Y, Stankus JJ, Soletti L, Wagner WR, Vorp DA, “Transient Elastic Support for Vein Grafts Using a Constricting Microfibrillar Polymer Wrap,” Biomaterials. 2008 Aug;29(22):3213-20. PMCID: PMC2486447. NIHMSID: NIHMS54309
Progressive destruction of the aortic extracellular matrix is a common feature of aortic aneurysm. In collaboration with Dr. Nancy Pleshko at Temple University, we have studied the distribution of two key extracellular matrix components, collagen and elastin, in human aneurysm biopsies. Dr. Pleshko’s technology centers on the use of Fourier Transform Infrared Imaging Spectroscopy. In this technique, the interaction of molecular bonds with varying wavelengths of infrared light is measured and molecular structures can be characterized based on signature spectral absorbance bands. The second derivative of the spectra can increase the ability to detect specific absorption bands by resolving overlapping bands in raw spectra. By studying these second derivative spectra, we were able to distinguish ECM components in the AAA wall samples, consistent with histochemically stained images. Spectroscopic imaging technology has the potential for translation to a clinical environment to examine ECM changes in a minimally invasive fashion using fiber optic technology, and this study will lay the groundwork for future in vivo clinical studies.
Infrared Spectroscopy to Map Extracellular Components in Abdominal Aortic Aneurysm Wall – Rabee Cheheltani, Jayashree Rao, David A. Vorp, Mohammad F. Kiani, Nancy Pleshko: BMES 2012, Atlanta
1. Cheheltani R, McGoverin CM, Rao J, Vorp DA, Kiani MF, Pleshko N, “Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta”, Analyst 2014 Jun 21;139(12):3039-47. PMID 24761431, PMCID: PMC4096121
Crohn’s disease is a clinically challenging inflammatory condition capable of afflicting the entire gastro-intestinal tract. A widely used surgical treatment for Crohn’s disease is a procedure called the Heineke-Mikulicz strictureplasty. In this procedure, a longitudinal cut is made in the intestinal wall and new sutures are added to redistribute wall stresses. Our goal has been to computationally model this procedure in order to better understand the intestinal remodeling which follows strictureplasty, and to design a better surgical solution (length of incision, number of sutures, etc.).
1. Tsamis A, Pocivavsek L, Vorp DA, “ Elasticity and geometry: a computational model of the Heineke-Mikulicz strictureplasty”, Biomechanics and Modeling in Mechanobiology, 2014 Nov;13(6):1185-98, PMID: 24671519
A unique feature of abdominal aortic aneurysm is the presence of an intraluminal thrombus (ILT). The growth of the ILT is progressive, and presents a “Jekyll and Hyde” situation. On the one hand, the ILT provides protection for the weakened aneurysmal wall by reducing the hemodynamic stresses on the wall. On the other hand, the ILT blocks the transmission of oxygen to the wall, leaving the wall in a hypoxic state. Notably, we have identified both macrophages and collagen fibers within the ILT, reflecting that there is dynamic remodeling of the ILT - this remodeling could theoretically contribute to (and/or limit!) aneurysm growth.
1. Vorp DA, Lee PC, Wang DHJ, Makaroun MS, Nemoto EM, Ogawa S, Webster MW, “Association of Intraluminal Thrombus in Abdominal Aortic Aneurysm with Local Hypoxia and Wall Weakening,” J Vasc Surg, 2001 Aug;34(2):291-99, PMID: 11496282.
2. Wang DHJ, Makaroun MS, Webster MW, Vorp DA, “Effect of Intraluminal Thrombus on Wall Stress in Patient-Specific Models of Abdominal Aortic Aneurysm,” J Vasc Surg, 36:598-604,2002 PMID: 12218961
3. Rao J, Brown B, Weinbaum JS, Ofstun E, Makaroun MS, Humphrey JD, Vorp DA, “Distinct macrophage phenotype and collagen organization within the intraluminal thrombus of abdominal aortic aneurysm”, Journal of Vascular Surgery, 2015 Sept;62(3):585-593, PMID: 26206580, PMCID: PMC4550501
Our lab has developed a mechanical loading paradigm (“Mechanical Panel”) that allows the exposure of cultured cells to three physiologic forces in parallel. These forces include cyclic stretching, cyclic hydrostatic pressure and laminar shear stress, the cellular responses to which can all be compared to each other as well as to static incubator (control) conditions. The cyclic stretching and laminar shear stress are imparted using systems commercially-available from FlexcellTM. To impart cyclic hydrostatic pressure loading to the cells, we developed a customized system. We also have the capability using the Flexcell Tissue TrainTM system to impart mechanical loading to 3D cellularized constructs. We chose to study the response of mesenchymal stem cells (MSCs) to mechanical forces in 2D (via the mechanical panel) and 3D (via the Tissue Train). We have found, among other things, that MSCs can differentiate towards smooth cell phenotype under the cyclic stretch both in 2D and 3D.
1. Maul TM, Chew DW, Nieponice A, Vorp DA, “Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation” Biomech Model Mechanobiol, 2011 Dec;10(6): 939-953, PMID: 21253809, PMCID: PMC3208754