David vorp

OBJECTIVE: Tissue-engineered vascular grafts containing adipose-derived mesenchymal stem cells offer an alternative to small-diameter vascular grafts currently used in cardiac and lower-extremity revascularization procedures. Adipose-derived, mesenchymal stem cell-infused, tissue-engineered vascular grafts have been shown to promote remodeling and vascular homeostasis in vivo and offer a possible treatment solution for those with cardiovascular disease. Unfortunately, the time needed to cultivate adipose-derived mesenchymal stem cells remains a large hurdle for tissue-engineered vascular grafts as a treatment option...

Vascular tissue engineering is an area of regenerative medicine that attempts to create functional replacement tissue for defective segments of the vascular network. One approach to vascular tissue engineering utilizes seeding of biodegradable tubular scaffolds with stem (and/or progenitor) cells wherein the seeded cells initiate scaffold remodeling and prevent thrombosis through paracrine signaling to endogenous cells. Stem cells have received an abundance of attention in recent literature regarding the mechanism of their paracrine therapeutic effect...

Nerve blocks are frequently performed by anesthesiologists to control pain. For sciatic nerve blocks, the optimal placement of the needle tip between its paraneural sheath and epineurial covering is challenging, even under ultrasound guidance, and frequently results in nerve puncture. We performed needle penetration tests on cadaveric isolated paraneural sheath (IPS), isolated nerve (IN), and the nerve with overlying paraneural sheath (NPS), and quantified puncture force requirement and fracture toughness of these specimens to assess their role in determining the clinical risk of nerve puncture...

High lethality of aortic dissection necessitates accurate predictive metrics for dissection risk assessment. The not infrequent incidence of dissection at aortic diameters <5.5 cm, the current threshold guideline for surgical intervention (Nishimura et al., 2014), indicates an unmet need for improved evidence-based risk stratification metrics. Meeting this need requires a fundamental understanding of the structural mechanisms responsible for dissection evolution within the vessel wall. We present a structural model of the repeating lamellar structure of the aortic media comprised of elastic lamellae and collagen fiber networks, the primary load-bearing components of the vessel wall...

Interleukin 33 (IL-33), an inflammatory and mechanically responsive cytokine, is an important component of a TLR4-dependent innate immune process in mucosal epithelium. Although TLR4 also plays a role in sensing biomechanical stretch, a pathway of stretch-induced TLR4-dependent IL-33 biosynthesis has not been revealed. In the current study, we show that short term (6 h) cyclic stretch (CS) of cultured murine respiratory epithelial cells (MLE-12) increased intracellular IL-33 expression in a TLR4 dependent fashion...

Age-related declines in skeletal muscle regeneration have been attributed to muscle stem cell (MuSC) dysfunction. Aged MuSCs display a fibrogenic conversion, leading to fibrosis and impaired recovery after injury. Although studies have demonstrated the influence of in vitro substrate characteristics on stem cell fate, whether and how aging of the extracellular matrix (ECM) affects stem cell behavior has not been investigated. Here, we investigated the direct effect of the aged muscle ECM on MuSC lineage specification...

OBJECTIVE: One of the rate-limiting barriers within the field of vascular tissue engineering is the lengthy fabrication time associated with expanding appropriate cell types in culture. One particularly attractive cell type for this purpose is the adipose-derived mesenchymal stem cell (AD-MSC), which is abundant and easily harvested from liposuction procedures. Even this cell type has its drawbacks, however, including the required culture period for expansion, which could pose risks of cellular transformation or contamination...

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture. Here, using our recently developed Fourier transform infrared imaging spectroscopy (FT-IRIS) method, we quantified collagen content and maturity in the wall of AAA tissues in pairs of specimens with different wall stresses...

Current commercial tensile testing systems use spring-loaded or other compression-based grips to clamp materials in place posing a problem for very soft or delicate materials that cannot withstand this mechanical clamping force. In order to perform uniaxial tensile tests on soft tissues or materials, we have created a novel vacuum-assisted anchor (VAA). Fibrin gels were subjected to uniaxial extension, and the testing data was used to determine material mechanical properties. Utilizing the VAA, we achieved successful tensile breaks of soft fibrin gels while finding statistically significant differences between the mechanical properties of gels fabricated at two different fibrinogen concentrations...

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue...

Many preclinical evaluations of autologous small-diameter tissue-engineered vascular grafts (TEVGs) utilize cells from healthy humans or animals. However, these models hold minimal relevance for clinical translation, as the main targeted demographic is patients at high cardiovascular risk such as individuals with diabetes mellitus or the elderly. Stem cells such as adipose-derived mesenchymal stem cells (AD-MSCs) represent a clinically ideal cell type for TEVGs, as these can be easily and plentifully harvested and offer regenerative potential...

Abdominal aortic aneurysm (AAA) intervention and surveillance is currently based on maximum transverse diameter, even though it is recognized that this might not be the best strategy. About 10% of patients with small AAA transverse diameters, for whom intervention is not considered, still rupture; while patients with large AAA transverse diameters, for whom intervention would have been recommended, have stable aneurysms that do not rupture. While maximum transverse diameter is easy to measure and track in clinical practice, one of its main drawbacks is that it does not represent the whole AAA and rupture seldom occurs in the region of maximum transverse diameter...

OBJECTIVE: Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions...

OBJECTIVE: Little is known about the etiologic factors that lead to the occurrence of intraluminal thrombus (ILT) during abdominal aortic aneurysm (AAA) development. Recent work has suggested that macrophages may play an important role in progression of a number of other vascular diseases, including atherosclerosis; however, whether these cells are present within the ILT of a progressing AAA is unknown. The purpose of this work was to define the presence, phenotype, and spatial distribution of macrophages within the ILT excised from six patients...

Determination of correlations between transmural mechanical and morphological properties of aorta would provide a quantitative baseline for assessment of preventive and therapeutic strategies for aortic injuries and diseases. A multimodal and multidisciplinary approach was adopted to characterize the transmural morphological properties of descending porcine aorta. Histology and multi-photon microscopy were used for describing the media layer micro-architecture in the circumferential-radial plane, and Fourier Transform infrared imaging spectroscopy was utilized for determining structural protein, and total protein content...

Wall stress is a powerful tool to assist clinical decisions in rupture risk assessment of abdominal aortic aneurysms. Key modeling assumptions that influence wall stress magnitude and distribution are the inclusion or exclusion of the intraluminal thrombus in the model and the assumption of a uniform wall thickness. We employed a combined numerical-experimental approach to test the hypothesis that abdominal aortic aneurysm (AAA) wall tissues with different thickness as well as wall tissues covered by different thrombus thickness, exhibit differences in the mechanical behavior...

OBJECTIVE: Blood vessel hemodynamics have profound influences on function and structure of vascular cells. One of the main mechanical forces influencing vascular smooth muscle cells (VSMC) is cyclic stretch (CS). Increased CS stimulates reactive oxygen species (ROS) production in VSMC, leading to their dedifferentiation, yet the mechanisms involved are poorly understood. This study was designed to test the hypothesis that pathological CS stimulates NADPH oxidase isoform 1 (Nox1)-derived ROS via MEF2B, leading to VSMC dysfunction via a switch from a contractile to a synthetic phenotype...

We recently reported a mechanistic model to link micro-architectural information to the delamination strength (Sd) of human ascending thoracic aorta (ATA). That analysis demonstrated that the number density (N) and failure energy (Uf) of the radially-oriented collagen fibers contribute to the Sd of both aneurysmal (ATAA) and non-aneurysmal (CTRL-ATA) aortic tissue. Among the set of ATAA samples, we studied specimens from patients displaying bicuspid (BAV) and tricuspid aortic valve (TAV) morphologic phenotypes...

AIM: Demonstrate that periadventitial delivery of adipose-derived mesenchymal stem cells (ADMSCs) slows aneurysm progression in an established murine elastase-perfusion model of abdominal aortic aneurysm (AAA). MATERIALS & METHODS: AAAs were induced in C57BL/6 mice using porcine elastase. During elastase perfusion, a delivery device consisting of a subcutaneous port, tubing and porous scaffold was implanted. Five days after elastase perfusion, 100,000 ADMSCs were delivered through the port to the aorta...

Introduction: Ureteral injuries such as avulsion are directly related to mechanical damage of the ureter. Understanding the tensile strength of this tissue may assist in prevention of iatrogenic injuries. Few published studies have looked at the mechanical properties of the animal ureter, and of those none have determined the tensile strength of the human ureter. Therefore, the purpose of this work was to determine the tensile strength of the human ureter. Materials and Methods: We harvested 11 human proximal ureters from patients who were undergoing nephrectomy for either kidney tumors or non-functioning kidney...