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Biomedical subjects

David A Vorp

Publications and source records attributed to David A Vorp.

At least 19 recordsLinked to original sources

Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix.

One of the major limitations in tissue engineering is cell sourcing. Multipotent progenitor cells appear to have many promising features for that purpose. Mechanical stimulation is known to play an important role in determining cell phenotype. The aim of this work was to investigate the effects of cyclic stretch on rat bone marrow derived progenitor cell (BMPC) morphology and smooth muscle-directed differentiation within a three-dimensional fibrin matrix. BMPCs were suspended in a fibrin gel, pipetted into the trough of Flexcell Tissue-Train plates, and stimulated with 10% longitudinal cyclic stretch at 1 Hz for 6 days. Unconstrained (stress- and strain-free) and static anchored (constrained but not stretched) samples were used as controls. Stress filament area per cell was increased in the stretched samples compared to static anchored and free-float controls. Cells in the free float controls were randomly aligned, while they aligned parallel to the direction of the stress or strain in the other groups. Immunofluorescence suggested an increased expression of smooth muscle markers (smooth muscle alpha actin and h1-calponin) in both stretched and constrained control samples, but not in unconstrained controls. Qualitative assessment suggested that collagen production was increased in both mechanically stimulated samples. Proliferation was inhibited in stretched samples compared to the constrained controls. This work suggests an ability of rat BMPCs to differentiate toward a smooth-muscle-cell-like lineage when exposed to biomechanical stimulation in a three-dimensional model. The observation that the constrained samples induced changes in BMPCs suggests that stress alone may be stimulatory, but addition of cyclic stretch appears to augment the responses.

Animals↗

Effects of wall calcifications in patient-specific wall stress analyses of abdominal aortic aneurysms.

It is generally acknowledged that rupture of an abdominal aortic aneurysm (AAA) occurs when the stress acting on the wall over the cardiac cycle exceeds the strength of the wall. Peak wall stress computations appear to give a more accurate rupture risk assessment than AAA diameter, which is currently used for a diagnosis. Despite the numerous studies utilizing patient-specific wall stress modeling of AAAs, none investigated the effect of wall calcifications on wall stress. The objective of this study was to evaluate the influence of calcifications on patient-specific finite element stress computations. In addition, we assessed whether the effect of calcifications could be predicted directly from the CT-scans by relating the effect to the amount of calcification present in the AAA wall. For 6 AAAs, the location and extent of calcification was identified from CT-scans. A finite element model was created for each AAA and the areas of calcification were defined node-wise in the mesh of the model. Comparisons are made between maximum principal stress distributions, computed without calcifications and with calcifications with varying material properties. Peak stresses are determined from the stress results and related to a calcification index (CI), a quantification of the amount of calcification in the AAA wall. At calcification sites, local stresses increased, leading to a peak stress increase of 22% in the most severe case. Our results displayed a weak correlation between the CI and the increase in peak stress. Additionally, the results showed a marked influence of the calcification elastic modulus on computed stresses. Inclusion of calcifications in finite element analysis of AAAs resulted in a marked alteration of the stress distributions and should therefore be included in rupture risk assessment. The results also suggest that the location and shape of the calcified regions--not only the relative amount--are considerations that influence the effect on AAA wall stress. The dependency of the effect of the wall stress on the calcification elastic modulus points out the importance of determination of the material properties of calcified AAA wall.

Aorta, Abdominal↗

A new experimental system for the extended application of cyclic hydrostatic pressure to cell culture.

Mechanical forces have been shown to be important stimuli for the determination and maintenance of cellular phenotype and function. Many cells are constantly exposed in vivo to cyclic pressure, shear stress, and/or strain. Therefore, the ability to study the effects of these stimuli in vitro is important for understanding how they contribute to both normal and pathologic states. While there exist commercial as well as custom-built devices for the extended application of cyclic strain and shear stress, very few cyclic pressure systems have been reported to apply stimulation longer than 48 h. However, pertinent responses of cells to mechanical stimulation may occur later than this. To address this limitation, we have designed a new cyclic hydrostatic pressure system based upon the following design variables: minimal size, stability of pressure and humidity, maximal accessibility, and versatility. Computational fluid dynamics (CFD) was utilized to predict the pressure and potential shear stress within the chamber during the first half of a 1.0 Hz duty cycle. To biologically validate our system, we tested the response of bone marrow progenitor cells (BMPCs) from Sprague Dawley rats to a cyclic pressure stimulation of 120/80 mm Hg, 1.0 Hz for 7 days. Cellular morphology was measured using Scion Image, and cellular proliferation was measured by counting nuclei in ten fields of view. CFD results showed a constant pressure across the length of the chamber and no shear stress developed at the base of the chamber where the cells are cultured. BMPCs from Sprague Dawley rats demonstrated a significant change in morphology versus controls by reducing their size and adopting a more rounded morphology. Furthermore, these cells increased their proliferation under cyclic hydrostatic pressure. We have demonstrated that our system imparts a single mechanical stimulus of cyclic hydrostatic pressure and is capable of at least 7 days of continuous operation without affecting cellular viability. Furthermore, we have shown for the first time that BMPCs respond to cyclic hydrostatic pressure by alterations in morphology and increased proliferation.

Animals↗

Ex vivo biomechanical properties of the female urethra in a rat model of birth trauma.

Stress urinary incontinence (SUI) is the involuntary release of urine during sudden increases in abdominal pressures. SUI is common in women after vaginal delivery or pelvic trauma and may alter the biomechanical properties of the urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases urethral basal tone and passive stiffness. This study aimed to assess the biomechanical properties of the urethra after VD in the baseline state, where basal muscle tone and extracellular matrix (ECM) are present, and in the passive state, where inactive muscle and ECM are present. Female rat urethras were isolated in a rat model of acute SUI induced by simulated birth trauma. Our established ex vivo system was utilized, wherein we applied intraluminal static pressures ranging from 0 to 20 mmHg. Outer diameter was measured via a laser micrometer. Measurements were recorded via computer. Urethral thickness was assessed histologically. Stress-strain responses of the urethra were altered by VD. Quantification of biomechanical parameters indicated that VD decreased baseline stiffness. The passive peak incremental elastic modulus of the distal segment in VD urethras was less than for controls (1.84 +/- 0.67 vs. 1.19 +/- 0.70 x 10(6) dyne/cm(2), respectively; P = 0.016). An increase was noted in passive low-pressure compliance values in proximal VD urethras compared with controls (9.44 +/- 2.43 vs. 4.62 +/- 0.60 mmHg(-1), respectively; P = 0.04). Biomechanical analyses suggest that VD alters urethral basal tone, proximal urethral compliance, and distal stiffness. Lack of basal smooth muscle tone, in combination with these changes in the proximal and distal urethra, may contribute to SUI induced by VD.

Animals↗

Effects of uniaxial cyclic strain on adipose-derived stem cell morphology, proliferation, and differentiation.

Cells and tissues in vivo are subjected to various forms of mechanical forces that are essential to their normal development and functions. The arterial blood vessel wall is continuously exposed to mechanical stresses such as pressure, strain, and shear due to the pulsatile nature of blood flow. Vascular smooth muscle cells (SMCs) populate the media of blood vessels and play important roles in the control of vasoactivity and the remodeling of the vessel wall. It is well documented that the phenotype and functions of vascular SMCs are not only regulated by chemical factors such as transforming growth factor-beta(1) (TGF-beta(1)), but also by mechanical factors such as uniaxial strain. The purpose of our study was to explore the effects of TGF-beta(1) alone or in combination with uniaxial cyclic strain on adipose-derived stem cell (ASC) morphology, proliferation, and differentiation. Low passage ASCs were stimulated with 10% strain at 1 Hz for 7 days, with or without TGF-beta(1). Cyclic strain inhibited proliferation, and caused alignment of the cells and of the F-actin cytoskeleton perpendicular to the direction of strain. Strain alone resulted in a decrease in the expression of early SMC markers alpha-SMA and h (1)-calponin. While the response of SMCs and other progenitor cells such as bone marrow stromal cells to mechanical forces has been extensively studied, the roles of these forces on ASCs remain unexplored. This work advances our understanding of the mechanical regulation of ASCs.

Actins↗

A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms.

The rupture risk of abdominal aortic aneurysms (AAAs) is thought to be associated with increased levels of wall stress. Finite element analysis (FEA) allows the prediction of wall stresses in a patient-specific, non-invasive manner. We have recently shown that it is important to include the intra-luminal thrombus (ILT), present in approximately 70% of AAA, into FEA simulations of AAA. All FEA simulations to date assume an isotropic, homogeneous material behavior for this material. The purpose of this work was to investigate the multi-axial biomechanical behavior of ILT and to derive an appropriate constitutive relation. We performed planar biaxial testing on the luminal layer of nine ILT specimens obtained fresh in the operating room (9 patients, mean age 71+/-4.5 years, mean diameter 5.9+/-0.4 cm), and a constitutive relation was derived from this data. Peak stretch and maximum tangential modulus (MTM) values were recorded for the equibiaxial protocol in both the circumferential (theta) and longitudinal (L) directions. Stress contour plots were used to investigate the presence of mechanical anisotropy, after which an appropriate strain energy function was fit to each of the specimen datasets. The peak stretch values for the luminal layer of the ILT were (mean+/-SEM) 1.18+/-0.02 and 1.13+/-0.02 in the theta and L directions, respectively (p=0.14). The MTM values were 20+/-2 and 23+/-3N/cm(2) in the theta and L directions, respectively (p=0.37). From these results and our observation of the symmetry of the stress contour plots for each specimen, we concluded that the use of an isotropic strain energy function for ILT is appropriate. Each specimen data set was then fit to a second-order polynomial strain energy function of the first invariant of the left Cauchy-Green strain tensor, resulting in an accurate fit (average R(2)=0.92+/-0.02; range 0.80-0.99). Comparison of our previously reported, uniaxially derived constitutive relation with the biaxially derived relation derived here shows large differences in the predicted mechanical response, underscoring the importance of the appropriate experimental methods used to derive constitutive relations. Further work is merited in an effort to produce more accurate predictions of wall stresses in patient-specific AAA, and viscoelastic behaviors of the ILT.

Aged↗

Towards a noninvasive method for determination of patient-specific wall strength distribution in abdominal aortic aneurysms.

The spatial distributions of both wall stress and wall strength are required to accurately evaluate the rupture potential for an individual abdominal aortic aneurysm (AAA). The purpose of this study was to develop a statistical model to non-invasively estimate the distribution of AAA wall strength. Seven parameters--namely age, gender, family history of AAA, smoking status, AAA size, local diameter, and local intraluminal thrombus (ILT) thickness--were either directly measured or recorded from the patients hospital chart. Wall strength values corresponding to these predictor variables were calculated from the tensile testing of surgically procured AAA wall specimens. Backwards-stepwise regression techniques were used to identify and eliminate insignificant predictors for wall strength. Linear mixed-effects modeling was used to derive a final statistical model for AAA wall strength, from which 95% confidence intervals on the model parameters were formed. The final statistical model for AAA wall strength consisted of the following variables: sex, family history, ILT thickness, and normalized transverse diameter. Demonstrative application of the model revealed a unique, complex wall strength distribution, with strength values ranging from 56 N/cm2 to 133 N/cm2. A four-parameter statistical model for the noninvasive estimation of patient-specific AAA wall strength distribution has been successfully developed. The currently developed model represents a first attempt towards the noninvasive assessment of AAA wall strength. Coupling this model with our stress analysis technique may provide a more accurate means to estimate patient-specific rupture potential of AAA.

Aging↗

A seeding device for tissue engineered tubular structures.

One of the challenges in the tissue engineering of tubular tissues and organs is the efficient seeding of porous scaffolds with the desired cell type and density in a short period of time, without affecting cell viability. Though different seeding techniques have been investigated, a fast, reproducible, and efficient bulk seeding method with uniform cellular distribution has yet to be reported. In this paper, a novel seeding device utilizing the synergistic effects of vacuum, centrifugal force and flow has been developed and analyzed. The device allows porous tubular scaffolds to be uniformly bulk seeded as well as luminally surface-seeded with cells. Porous tubular polymer scaffolds were bulk and surface-seeded with cell suspensions, and cell viability and seeding efficiency were subsequently assessed. A rigorous quantitative analysis of shear stresses acting on the cells during the seeding process, and of cell location within the scaffolds following seeding was also performed. Our results showed that the scaffolds were uniformly seeded along the longitudinal and circumferential directions within the tube wall without affecting cell viability or exposing them to excessive shear stresses.

Animals↗

The effects of aneurysm on the biaxial mechanical behavior of human abdominal aorta.

The biomechanical response of normal and pathologic human abdominal aortic tissue to uniaxial loading conditions is insufficient for the characterization of its three-dimensional (3D) mechanical behavior. Planar biaxial mechanical evaluation allows for 3D constitutive modeling of nearly incompressible tissues, as well as the investigation of the nature of mechanical anisotropy. In the current study, 26 abdominal aortic aneurysm (AAA) tissue samples and 8 age-matched (> 60 years of age) nonaneurysmal abdominal aortic (AA) tissue samples were obtained and tested using a tension-controlled biaxial testing protocol. Graphical response functions (Sun et al., 2003. J. Biomech. Eng. 125, 372-380) were used as a guide to describe the pseudo-elastic response of AA and AAA. Based on the observed pseudo-elastic response, a four-parameter exponential strain energy function developed by Vito (1990. J. Biomech. Eng. 112, 153-159) was used from which both an individual specimen and group material parameter sets were determined for both AA and AAA. Peak Green strain values in the circumferential (Ethetatheta,max) and longitudinal (ELL,max) directions under an equibiaxial tension of 120 N/m were also compared. The strain energy function fit all of the individual specimens well with an average R2 of 0.95 +/- 0.02 and 0.90 +/- 0.02 (mean +/- SEM) for the AA and AAA groups, respectively. The average Ethetatheta,max at 200 N/m equibiaxial tension was found to be significantly smaller for AAAs as compared to AAs (0.07 +/- 0.01 versus 0.13 +/- 0.03, respectively; p < 0.01). There was also a pronounced increase in the circumferential stiffness for AAA tissue as compared to AA tissue, indicating a larger degree of anisotropy for this tissue as compared to age-matched AA tissue. We also observed that the four-parameter Fung-elastic model was not able to fit the AAA tissue mechanical response using physically realistic material parameter values. It was concluded that aneurysmal degeneration of the abdominal aorta is associated with an increase in mechanical anisotropy, with preferential stiffening in the circumferential direction.

Anisotropy↗

Functional analysis of active urethral closure mechanisms under sneeze induced stress condition in a rat model of birth trauma.

PURPOSE: We evaluated changes in the urethral closure mechanism under a sneeze induced stress condition in a rat model of birth trauma. MATERIALS AND METHODS: Four days after vaginal distention induced by balloon catheter inflation in the vagina sneezing was induced while recording intravesical pressure with the rat under urethane anesthesia to evaluate sneeze induced leak point pressure, defined as the lowest pressure inducing fluid leakage from the urethral meatus during sneezing. Sneeze induced responses in the bladder and proximal or mid urethra were also measured using microtip transducer catheters. RESULTS: In 5 sham operated rats no leakage was observed from the urethral meatus during sneezing, which produced an increase in intravesical pressure of up to 34 cm H(2)O. However, in 5 of 6 rats with vaginal distention leakage during sneezing was observed with a sneeze leak point pressure of 26.2 cm H(2)O. In the mid urethra microtip transducer catheters revealed that pressure increases during sneezing were greater than those in the bladder but they were significantly decreased in the 5 incontinent vaginal distention rats. However, sneeze induced responses at the proximal urethra, which were similar to those in the bladder, were not different in sham operated and incontinent vaginal distention rats. CONCLUSIONS: Sneeze induced stress urinary incontinence in a rat model of birth trauma was caused by decreased active closure mechanisms at the mid urethra without affecting the passive transmission of abdominal pressure in the proximal urethra.

Animals↗

Biomechanical properties of ruptured versus electively repaired abdominal aortic aneurysm wall tissue.

OBJECTIVE: The purpose of this study was to evaluate and compare the biomechanical properties of abdominal aortic aneurysm (AAA) wall tissue from patients who experienced AAA rupture with that of those who received elective repair. METHODS: Rectangular, circumferentially oriented AAA wall specimens (approximately 2.5 cm x 7 mm) were obtained fresh from the operating room from patients undergoing surgical repair. The width and thickness were measured for each specimen by using a laser micrometer before testing to failure with a uniaxial tensile testing system. The force and deformation applied to each specimen were measured continuously during testing, and the data were converted to stress and stretch ratio. The tensile strength was taken as the peak stress obtained before specimen failure, and the distensibility was taken as the stretch ratio at failure. The maximum tangential modulus and average modulus were also computed according to the peak and average slope of the stress-stretch ratio curve. RESULTS: Twenty-six specimens were obtained from 16 patients (aged 73 +/- 3 years [mean +/- SEM]) undergoing elective repair of their AAA (diameter, 7.0 +/- 0.5 cm). Thirteen specimens were resected from nine patients (aged 73 +/- 3 years; P = not significant in comparison to the electively repaired AAAs) during repair of their ruptured AAA (diameter, 7.8 +/- 0.6 cm; P = not significant). A significant difference was noted in wall thickness between ruptured and elective AAAs: 3.6 +/- 0.3 mm vs 2.5 +/- 0.1 mm, respectively (P < .001). The tensile strength of the ruptured tissue was found to be lower than that for the electively repaired tissue (54 +/- 6 N/cm2 vs 82 +/- 9.0 N/cm2; P = .04). Considering all specimens, no significant correlation was noted between tensile strength and diameter (R = -0.10; P = .55). Tensile strength, however, had a significant negative correlation with wall thickness (R = -0.42; P < .05) and a significant positive correlation with the tissue maximum tangential modulus (R = 0.76; P < .05). CONCLUSIONS: Our data suggest that AAA rupture is associated with aortic wall weakening, but not with wall stiffening. A widely accepted indicator for risk of aneurysm rupture is the maximum transverse diameter. Our results suggest that AAA wall strength, in large aneurysms, is not related to the maximum transverse diameter. Rather, wall thickness or stiffness may be a better predictor of rupture for large AAAs.

Aged↗

A biomechanics-based rupture potential index for abdominal aortic aneurysm risk assessment: demonstrative application.

Abdominal aortic aneurysms (AAAs) can typically remain stable until the strength of the aortic wall is unable to withstand the forces acting on it as a result of the luminal blood pressure, resulting in AAA rupture. The clinical treatment of AAA patients presents a dilemma for the surgeon: surgery should only be recommended when the risk of rupture of the AAA outweighs the risks associated with the interventional procedure. Since AAA rupture occurs when the stress acting on the wall exceeds its strength, the assessment of AAA rupture should include estimates of both wall stress and wall strength distributions. The present work details a method for noninvasively assessing the rupture potential of AAAs using patient-specific estimations the rupture potential index (RPI) of the AAA, calculated as the ratio of locally acting wall stress to strength. The RPI was calculated for thirteen AAAs, which were broken up into ruptured (n = 8 and nonruptured (n = 5) groups. Differences in peak wall stress, minimum strength and maximum RPI were compared across groups. There were no statistical differences in the maximum transverse diameters (6.8 +/- 0.3 cm vs. 6.1 +/- 0.5 cm, p = 0.26) or peak wall stress (46.0 +/- 4.3 vs. 49.9 +/- 4.0 N/cm(2), p = 0.62) between groups. There was a significant decrease in minimum wall strength for ruptured AAA (81.2 +/- 3.9 and 108.3 +/- 10.2 N/cm(2), p = 0.045). While the differences in RPI values (ruptured = 0.48 +/- 0.05 vs. nonruptured = 0.36 +/- 0.03, respectively; p = 0.10) did not reach statistical significance, the p-value for the peak RPI comparison was lower than that for both the maximum diameter (p = 0.26) and peak wall stress (p = 0.62) comparisons. This result suggests that the peak RPI may be better able to identify those AAAs at high risk of rupture than maximum diameter or peak wall stress alone. The clinical relevance of this method for rupture assessment has yet to be validated, however, its success could aid clinicians in decision making and AAA patient management.

Aortic Aneurysm, Abdominal↗

Gender-related differences in the tensile strength of abdominal aortic aneurysm.

A recent study investigated the association of gender with the growth rate of AAAs and found a significant increase in the growth rate of AAAs in women than in men. On the basis of these observations, we hypothesize that there are gender-associated differences in AAA wall integrity and mechanical strength. The purpose of this study was to explore this hypothesis by comparing the tensile strength of freshly resected AAA tissue specimens between women and men. Seventy-six rectangular specimens (20 mm long x 5 mm wide) from 34 patients (24 male, 10 female) were excised from the anterior wall of patients undergoing open repair of their abdominal aortic aneurysm and tested in a uniaxial tensile tester. Ultimate tensile strength (UTS) was taken as the peak stress obtained before specimen failure. While there were no statistical differences in strength between specimens taken from male and female patients, there was a trend toward a decrease in strength in females as compared to males (87.6 +/- 6.7 N/cm(2) vs. 67.6 +/- 8.1 N/cm(2), p = 0.09). To the authors knowledge this work represents the first report of differences in biomechanical properties as a function of gender. The nearly significant decrease in UTS in women versus men reported here may be important in assessing the risk of rupture in AAA. Further testing is warranted to confirm the current trends.

Aortic Aneurysm, Abdominal↗

Biomechanical characterization of the urethral musculature.

Rigorous study of the associations between urethral structural anatomy and biomechanical function is necessary to advance the understanding of the development, progression, and treatment of urethral pathologies. An ex vivo model was utilized to define the relative biomechanical contributions of the active (muscle) elements of the female urethra relative to its passive (noncontractile) elements. Whole urethras from female, adult rats were tested under a range of applied intraluminal pressures (0 to 20 mmHg) as a laser micrometer simultaneously measured midurethral outer diameter. Active tissue characterization was performed during induced contraction of either smooth muscle alone (N(omega)-nitro-l-arginine, phenylephrine), striated muscle alone (sodium nitroprusside, atropine, hexamethonium, acetylcholine), or during collective activation of both muscles (N(omega)-nitro-l-arginine, phenylephrine, acetylcholine). The subsequent collection of paired passive biomechanical responses permitted the determination of parameters related to intrinsic muscle contractile function. Activation of each muscle layer significantly influenced the biomechanical responses of the tissue. Measures of muscle responsiveness over a wide range of sustained opposing pressures indicated that an activated striated muscle component was approximately one-third as effective as activated smooth muscle in resisting tissue deformation. The maximum circumferential stress generated by the striated muscle component under these conditions was also determined to be approximately one-third of that generated by the smooth muscle (748 +/- 379 vs. 2,229 +/- 409 N/m(2)). The experiments quantitatively reveal the relative influence of the intrinsic urethral smooth and striated muscle layers with regard to their effect on the mechanical properties and maximum functional responses of the urethra to applied intralumenal stresses in the complete absence of extrinsic influences.

Animals↗

Molecular aspects of vascular tissue engineering.

Cardiovascular disease remains the number one cause of death in the United States. Most current surgical procedures to alleviate this disease rely on the availability of suitable small diameter vascular grafts, which are constrained by several limitations. Tissue engineering brings new hope to this field, but still faces many challenges. This review focuses on the molecular aspects of the different components of vascular tissue engineering. The topics addressed include the cell type, extracellular matrix, and physical and biochemical stimulation with respect to their role in the development of a tissue engineered vascular graft.

Animals↗

Analytically derived material properties of multilaminated extracellular matrix devices using the ball-burst test.

Xenogeneic extracellular matrices (ECMs) have been shown to be effective as naturally occurring scaffolds for soft-tissue repair. As acellular tissue substitutes at the time of surgical implantation, ECMs are subjected to the mechanical forces and micro-environmental conditions representative of the anatomical location in which they are placed. Ideally such natural scaffolds would possess mechanical properties that allow for normal tissue function in and around the implant site. The ball-burst test was used to simulate biaxial forces and to determine the strength of the ECM scaffold under a relevant physiological loading condition. The ball-burst test, in itself, does not quantify intrinsic mechanical properties and therefore a methodology was developed to determine the maximum stress resultant tangent modulus (MSRTM) or the maximum stress tangent modulus (MSTM), stress to failure (sigma(f)), failure stress resultant (N(f)), ball-burst pressure (P), and maximum elongation (lambda(max)) from the raw ball-burst data obtained at a constant-rate of transverse. The analytical methodology was compared to finite element simulations and showed good correlation with the analytical solution presented. The proposed approximations were used to compute biaxial failure properties for a variety of multilaminate ECM devices with varying number of layers, disinfection and sterilization, and organ origin.

Animals↗

Esophageal reconstruction with ECM and muscle tissue in a dog model.

An in vivo study was conducted to determine if an extracellular matrix (ECM) scaffold co-localized with autologous muscle tissue could achieve constructive remodeling of esophageal tissue without stricture. ECM derived from the porcine urinary bladder was processed, decellularized, configured into a tube shape, and terminally sterilized for use as a bioscaffold for esophageal reconstruction in a dog model. Twenty-two dogs were divided into four groups, three groups of five and one group of seven. Groups 1 and 2 were repaired with either ECM alone or muscle tissue alone, respectively. Groups 3 and 4 were repaired with ECM plus either a partial (30%) covering with muscle tissue or a complete (100%) covering with muscle tissue, respectively. Animals in groups 1 and 2 were sacrificed within approximately 3 weeks because of the formation of intractable esophageal stricture. Four of five dogs in group 3 and six of seven dogs in group 4 were survived for 26 days to 230 days and showed constructive remodeling of esophageal tissue with the formation of well organized esophageal tissue layers, minimal stricture, esophageal motility, and a normal clinical outcome. Mechanical testing of a subset of the remodeled esophageal tissue from animals in groups 3 and 4 showed progressive remodeling from a relatively stiff, non-compliant ECM tube structure toward a tissue with near normal biomechanical properties. We conclude that ECM bioscaffolds plus autologous muscle tissue, but not ECM scaffolds or muscle tissue alone, can facilitate the in situ reconstitution of structurally and functionally acceptable esophageal tissue.

Animals↗

Biomechanical determinants of abdominal aortic aneurysm rupture.

Rupture of abdominal aortic aneurysm (AAA) represents a significant clinical event, having a mortality rate of 90% and being currently ranked as the 13th leading cause of death in the US. The ability to reliably evaluate the susceptibility of a particular AAA to rupture on a case-specific basis could vastly improve the clinical management of these patients. Because AAA rupture represents a mechanical failure of the degenerated aortic wall, biomechanical considerations are important to understand this process and to improve our predictions of its occurrence. Presented here is an overview of research to date related to the biomechanics of AAA rupture. This includes a summary of results related to ex vivo and in vivo mechanical testing, noninvasive AAA wall stress estimations, and potential mechanisms of AAA wall weakening. We conclude with a demonstration of a biomechanics-based approach to predicting AAA rupture on a patient-specific basis, which may ultimately prove to be superior to the widely and currently used maximum diameter criterion.

Animals↗