Publications

The two primary load-bearing components of the connective fiber micro-architecture of aorta are the proteins elastin and collagen. The structure of elastin and collagen fibers is important to support the proper function of the aorta, and alteration of the quantity and/or arrangement of these fibers can lead to mechanical and functional changes associated with aortic disease. Therefore, an adequate quantification of the micro-architecture of elastin and collagen fibers in the aortic wall would provide insight into the influence of micro-architecture on the biomechanical response of the aorta in health and disease.

Abstract Background: The pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to quantify the mechanical and morphological properties of ovine PAC. Methods: Ovine brain samples (n=10) were removed from the skull and tissue was harvested within 30 minutes post-mortem. To access the PAC, ovine skulls were split medially from the occipital region down the nasal bone on the superior and inferior aspects of the skull. A template was used to remove arachnoid samples from the left and right sides of the frontal and occipital regions of the brain. 10 ex-vivo samples were tested with uniaxial tension at 2 mm s -1 , average strain rate of 0.59 s -1 , until failure at <5 hours post extraction. The force and displacement data were acquired at 100 Hz using LabVIEW. PAC tissue collagen fiber microstructure was characterized using second-harmonic generation (SHG) imaging on a subset of n=4 stained tissue samples. To differentiate transverse blood vessels from SAT by visualization of cell nuclei and endothelial cells, samples were stained with DAPI and anti-von Willebrand Factor, respectively. The Mooney-Rivlin model for average stress-strain curve fit was used to model PAC material properties. Results: The elastic modulus, ultimate stress, and ultimate strain were found to be 7.7±3.0 MPa, 2.7±0.76 MPa, and 0.60±0.13, respectively. No statistical significance was found across brain dissection locations in terms of biomechanical properties. SHG images were post-processed to obtain average SAT fiber intersection density, concentration, porosity, tortuosity, segment length, orientation, radial counts, and diameter as 0.23%, 26.14%, 73.86%, 1.07±0.28, 17.33±15.25 µm, 84.66±49.18º, 8.15%, 3.46±1.62 µm, respectively. Conclusion: For the sizes, strain, and strain rates tested, our results suggest that ovine PAC mechanical behavior is isotropic, and that the Mooney-Rivlin model is an appropriate curve-fitting constitutive equation for obtaining material parameters of PAC tissues.

Periadventitial stem cell delivery prevented the expansion of an established aneurysm between days 5 and 14 after elastase perfusion.

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. However, very little of this mechanistic research has been performed under the aegis of vascular tissue engineering. Therefore, the scope of this review includes the current state of TEVGs generated using the incorporation of stem cells in biodegradable scaffolds and potential cell-free directions for TEVGs based on stem cell secreted products. The current generation of stem cell-seeded vascular scaffolds are based on the premise that cells should be obtained from an autologous source. However, the reduced regenerative capacity of stem cells from certain patient groups limits the therapeutic potential of an autologous approach. This limitation prompts the need to investigate allogeneic stem cells or stem cell secreted products as therapeutic bases for TEVGs. The role of stem cell derived products, particularly extracellular vesicles (EVs), in vascular tissue engineering is exciting due to their potential use as a cell-free therapeutic base. EVs offer many benefits as a therapeutic base for functionalizing vascular scaffolds such as cell specific targeting, physiological delivery of cargo to target cells, reduced immunogenicity, and stability under physiological conditions. However, a number of points must be addressed prior to the effective translation of TEVG technologies that incorporate stem cell derived EVs such as standardizing stem cell culture conditions, EV isolation, scaffold functionalization with EVs, and establishing the therapeutic benefit of this combination treatment.

Patients with diabetes mellitus (DM) suffer impaired lower urinary tract dysfunctions. The purpose of the current study was to evaluate the effects of DM on the passive biomechanical properties of the female rat urethra. DM was induced by injection of streptozotocin. Urethras were excised and mounted in an ex-vivo testing system. EDTA was added to the bath to inactivate smooth muscle. Continuous outer diameter measurements were made at proximal, middle, and distal portions of the urethra with a laser micrometer during stepwise increases of static, intraurethral pressure (0 to 20 mmHg). Compliance and beta stiffness were calculated from measured data. Healthy urethras served as controls. Statistical comparisons were made via ANOVA. The control tissue was most compliant proximally and decreased significantly along the length. This compliance gradient vanished with DM. A significant decrease in compliance and increase in beta stiffness was noted for 10 wk DM compared to controls. These findings suggest that DM has a large effect on the biomechanical properties of the urethra.

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.

Dataset containing the raw and processed data required to reproduce the findings related to the characterisation of human male urethra tissue published in https://doi.org/10.1016/j.biomaterials.2021.120651

Continuous flow ventricular assist devices (CFVADs) could revolutionize the industry, but effects on the vasculature are not well understood. The purpose of this work was to examine the effects of diminished pulse on arterial microstructure. Arterial segments were removed at the time of implantation (baseline: n=5) of a CFVAD into male dairy calves (flow was maintained at ± 50% of cardiac output). Another arterial segment was removed after 30 days (necropsy: n=3). Rings, of 2 mm width, were cut from the end of each vessel, embedded in freezing medium and frozen. The remaining segment was used for mechanical and vasoresponse testing (previously reported). Once frozen, five 6-micron sections were cut from each ring so that the staining could be repeated five times for each sample. Images were taken at 10x magnification and analyzed using Bioquant Nova software. Collagen and elastin content were recorded as a percentage of total cross-sectional area and each result reported as the average of the five measured values for each sample. Our results did not indicate significant differences between baseline and necropsy in either collagen (35.12+-10.8% vs 38.59+-1.8%, p<0.52) or elastin (10.67+-3.5% vs 13.85+-2.2%, p<0.16) content. This finding supports our previous result that there were no significant differences in the mechanical properties or vasoresponse between baseline and necropsy. Studies are ongoing to examine long-term (120 days) implantation effects, where direct correlations will be made between changes in arterial microstructure and changes in mechanical properties and vasoresponse.

The autologous saphenous vein graft remains the graft of choice for 95% of surgeons performing coronary artery or peripheral bypass procedures. Within the first 5 years after implantation, 20%–40% of arterial vein grafts (AVG) fail due to intimal hyperplasia (IH)1. This adverse pathological response by AVGs may be in part due to their abrupt exposure to the significantly elevated circumferential wall stress associated with the arterial system2. We believe that if an AVG is given an ample opportunity to adapt and remodel to the stresses of the arterial environment, cellular injury may be reduced, thus limiting the initiating mechanisms of IH.