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Vascular graft failure has persisted as a major clinical problem. Mechanical, structural, and transport properties of vascular grafts are critical factors that substantially affect their function and thus the outcome of implantation. The manufacturing method, post‐processing technique, and material of choice have a significant impact on these properties. The goal of this work is to use thermal treatment to modulate the transport properties of PCL‐based vascular engineered constructs. To this end, we electrospun PCL tubular constructs and thermally bonded the electrospun fibers in a convective oven at various temperatures (54, 57, and 60°C) and durations of treatment (15, 30, and 45 s). The effects of fiber thermal bonding (thermobonding) on the transport, mechanical, and structural properties of PCL tubular constructs were characterized. Increasing the temperature and treatment duration enhanced the degree of thermobonding by removing the interconnected void and fusing the fibers. Thermobonding at 57°C and 60°C for longer than 30 s increased the median tangential modulus (E = 126.1 MPa, [IQR = 20.7]), mean suture retention (F = 193.8 g, [SD = 18.5]), and degradation rate while it decreased the median permeability (kA = 0 m/s), and median thickness (t = 60 μm, [IQR = 2.5]). In particular, the thermobonding at 57°C allowed a finer modulation of permeability via treatment duration. We believe that the thermobonding method can be utilized to modulate the properties of vascular engineered constructs which can be useful in designing functional vascular grafts. [ABSTRACT FROM AUTHOR]

Background: The biomechanical behavior of the human abdominal aorta has been studied with great interest primarily due to its propensity to develop such maladies as atherosclerotic occlusive disease, dissections, and aneurysms. The purpose of this study was to investigate the age-related biaxial biomechanical behavior of human infrarenal aortic tissue. Methods of Approach: A total of 18 samples (13 autopsy, 5 organ donor) were harvested from patients in each of three age groups: Group 1 (60years old, n =6). Each specimen was tested biaxially using a tension-controlled protocol which spanned a large portion of the strain plane. Response functions fit to experimental data were used as a tool to guide the appropriate choice of the strain energy function W. Results: Under an equibiaxial tension of 120 N/m, the average peak stretch values in the circumferential direction for Groups 1, 2, and 3 were (mean[+ or -]SD) 1.46[+ or -] 0.07, 1.15 [+ or -] 0.07, and 1.11 [+ or -] 0.06, respectively, while the peak stretch values in the longitudinal direction were 1.41[+ or -]0.03, 1.19 [+ or -] 0.11, and 1.10_+0.04, respectively. There were no significant differences between the average longitudinal and circumferential peak stretch within each group (p > 0.1), but both of these values were significantly less (p < 0.001) for Groups 2 and 3 when compared to Group 1. Patients in Group 1 were modeled using a polynomial strain energy function HI, while patients in Groups 2 and 3 were modeled using an exponential form of W, suggesting an age-dependent shift in the mechanical response of this tissue. Conclusion: The biaxial tensile testing results reported here are, to our knowledge, the first given for the human infrarenal aorta and reinforce the importance of determining the functional form of W from experimental data. Such information may be useful for the clinician or researcher in identifying key changes in the biomechanical response of abdominal aorta in the presence of an aneurysm. Keywords: Abdominal Aorta, Biaxial, Constitutive Model, Biomechanics

Tissue engineered vascular grafts (TEVGs) have the ability to be tuned to match a target vessel's compliance, diameter, wall thickness, and thereby prevent compliance mismatch. In this work, TEVG compliance was manipulated by computationally tuning its layered composition or by manipulating a crosslinking agent (genipin). In particular, these three acelluluar TEVGs were compared: a compliance matched graft (CM g e l - high gelatin content); a hypocompliant PCL graft (HYPO p c l - high polycaprolactone content); and a hypocompliant genipin graft (HYPO g e n - equivalent composition as CM g e l but hypocompliant via increased genipin crosslinking). All constructs were implanted interpositionally into the abdominal aorta of 21 Sprague Dawley rats (n = 7 , males=11, females=10) for 28 days, imaged in-vivo using ultrasound, explanted, and assessed for remodeling using immunofluorescence and two photon excitation fluorescence imaging. Compliance matched grafts remained compliance-matched in-vivo compared to the hypocompliant grafts through 4 weeks (p < 0.05). Construct degradation and cellular infiltration was increased in the CM g e l and HYPO g e n TEVGs. Contractile smooth muscle cell markers in the proximal anastomosis of the graft were increased in the CM g e l group compared to the HYPO p c l (p = 0.007) and HYPO g e n grafts (p = 0.04). Both hypocompliant grafts also had an increased pro-inflammatory response (increased ratio of CD163 to CD86 in the mid-axial location) compared to the CM g e l group. Our results suggest that compliance matching using a computational optimization approach leads to the improved acute (28 day) remodeling of TEVGs. To the authors' knowledge, this is the first in-vivo rat study investigating TEVGs that have been computationally optimized for target vessel compliance. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Glaucoma is the second leading cause of irreversible blindness in the world with a higher prevalence in those of African Descent (AD) and Hispanic Ethnicity (HE) than in those of European Descent (ED). The objective of this study was to investigate the pressure dependent biomechanical response of the lamina cribrosa (LC) in normal human donor tissues from these racioethnic backgrounds. Pressure inflation tests were performed on 24 human LCs (n = 9 AD, n = 6 ED, and n = 9 HE) capturing the second harmonic generation (SHG) signal of collagen at 5, 15, 30, and 45 mmHg from an anterior view. A non-rigid image registration technique was utilized to determine the 3D displacement field in each LC from which 3D Green strains were calculated. The peak shear strain in the superior quadrant of the LC in those of ED was significantly higher than in those of AD and HE (p-value = 0.005 & 0.034, respectively) where ED = 0.017 [IQR = 0.012–0.027], AD = 0.0002 [IQR = −0.001–0.007], HE = 0.0016 [IQR = −0.002–0.012]). There were also significant differences in the regional strain heterogeneity in those of AD and HE that were absent in those of ED. This work represents, to our knowledge, the first ex-vivo study identifying significant differences in the biomechanical response of the LC in populations at increased risk of glaucoma. Future work will be necessary to assess if and how these differences play a role in predisposing those of Hispanic Ethnicity and African Descent to the onset and/or progression of primary open angle glaucoma. Statement of significance Glaucoma is the second leading cause of irreversible blindness in the world and occurs more frequently in those of African Descent and Hispanic Ethnicity than in those of European Descent. To date, there has been no ex-vivo study quantifying differences in the biomechanical response of the non-glaucomatous lamina cribrosa (LC) across these racioethnic backgrounds. In this work we report, for the first time, differences in the pressure dependent biomechanical response of LC across different racioethnic groups as quantified using nonlinear optical microscopy. This study lays the foundation for future work investigating if and how these differences may play a role in predisposing those at increased risk to the onset and/or progression of primary open angle glaucoma. [ABSTRACT FROM AUTHOR]

Although the drug-eluting stent (DES) has dramatically reduced the rate of coronary restenosis, it still occurs in up to 20% of patients with a DES. Monitoring drug delivery could be one way to decrease restenosis rates. We demonstrate real-time photoacoustic imaging and spectroscopy (PAIS) using a wavelength-tunable visible laser and clinical ultrasound scanner to track cardiac drug delivery. The photoacoustic signal was initially calibrated using porcine myocardial samples soaked with a known concentration of a drug surrogate (DiI). Next, an in situ coronary artery was perfused with DiI for 20 min and imaged to monitor dye transport in the tissue. Finally, a partially DiI-coated stent was inserted into the porcine brachiocephalic trunk for imaging. The photoacoustic signal was proportional to the DiI concentration between 2.4 and 120 μg/ml, and the dye was detected over 1.5 mm from the targeted coronary vessel. Photoacoustic imaging was also able to differentiate the DiI-coated portion of the stent from the uncoated region. These results suggest that PAIS can track drug delivery to cardiac tissue and detect drugs loaded onto a stent with sub-mm precision. Future work using PAIS may help improve DES design and reduce the probability of restenosis. [ABSTRACT FROM AUTHOR]

Progressively deteriorating visual field is a characteristic feature of primary open-angle glaucoma (POAG), and the biomechanics of optic nerve head (ONH) is believed to be important in its onset. We used porohyperelasticity to model the complex porous behavior of ocular tissues to better understand the effect variations in ocular material properties can have on ONH biomechanics. An axisymmetric model of the human eye was constructed to parametrically study how changes in the permeabilities of retina–Bruch's–choroid complex, sclera, uveoscleral pathway, and trabecular meshworkas well as how changes in the stiffness of the lamina cribrosa (LC) and sclera affect IOP, LC strains, and translaminar interstitial pressure gradients (TLIPG). Decreasingfrom 5 × 10− 12to 5 × 10− 13 m/s increased IOP and LC strains by 17%, and TLIPG by 21%. LC strains increased by 13% and 9% when the scleral and LC moduli were decreased by 48% and 50%, respectively. In addition to the trabecular meshwork and uveoscleral pathway, the retina–Bruch's–choroid complex had an important effect on IOP, LC strains, and TLIPG. Changes inand scleral modulus resulted in nonlinear changes in the IOP, and LC strains especially at the lowestand. This study demonstrates that porohyperelastic modeling provides a novel method for computationally studying the biomechanical environment of the ONH. Porohyperelastic simulations of ocular tissues may help provide further insight into the complex biomechanical environment of posterior ocular tissues in POAG. [ABSTRACT FROM PUBLISHER]

The purpose of this manuscript is to establish a unified theory of porohyperelasticity with transport and growth and to demonstrate the capability of this theory using a finite element model developed in MATLAB. We combine the theories of volumetric growth and mixed porohyperelasticity with transport and swelling (MPHETS) to derive a new method that models growth of biological soft tissues. The conservation equations and constitutive equations are developed for both solid-only growth and solid/fluid growth. An axisymmetric finite element framework is introduced for the new theory of growing MPHETS (GMPHETS). To illustrate the capabilities of this model, several example finite element test problems are considered using model geometry and material parameters based on experimental data from a porcine coronary artery. Multiple growth laws are considered, including time-driven, concentration-driven, and stress-driven growth. Time-driven growth is compared against an exact analytical solution to validate the model. For concentration-dependent growth, changing the diffusivity (representing a change in drug) fundamentally changes growth behavior. We further demonstrate that for stress-dependent, solid-only growth of an artery, growth of an MPHETS model results in a more uniform hoop stress than growth in a hyperelastic model for the same amount of growth time using the same growth law. This may have implications in the context of developing residual stresses in soft tissues under intraluminal pressure. To our knowledge, this manuscript provides the first full description of an MPHETS model with growth. The developed computational framework can be used in concert with novel in-vitro and in-vivo experimental approaches to identify the governing growth laws for various soft tissues. [ABSTRACT FROM AUTHOR]

Unilateral vocal-fold paralysis (UVP) occurs when one of the vocal folds becomes paralyzed due to damage to the recurrent laryngeal nerve (RLN). Individuals with UVP experience problems with speaking, swallowing, and breathing. Nearly two-thirds of all cases of UVP is associated with impaired function of the left RLN, which branches from the vagus nerve within the thoracic cavity and loops around the aorta before ascending to the larynx within the neck. We hypothesize that this path predisposes the left RLN to a supraphysiological, biomechanical environment, contributing to onset of UVP. Specifically, this research focuses on the identification of the contribution of the aorta to onset of left-sided UVP. Important to this goal is determining the relative influence of the material properties of the RLN and the aorta in controlling the biomechanical environment of the RLN. Finite element analysis was used to estimate the stress and strain imposed on the left RLN as a function of the material properties and loading conditions. The peak stress and strain in the RLN were quantified as a function of RLN and aortic material properties and aortic blood pressure using Spearman rank correlation coefficients. The material properties of the aortic arch showed the strongest correlation with peak stress [ρ = 0.63, 95% confidence interval (CI), -1.00 to -0.25] and strain (ρ = 0.62, 95% CI, -0.99 to -0.24) in the RLN. Our results suggest an important role for the aorta in controlling the biomechanical environment of the RLN and potentially in the onset of left-sided UVP that is idiopathic. [ABSTRACT FROM AUTHOR]

Poly(ester-urethane-urea) (PEUU) is one of many synthetic biodegradable elastomers under scrutiny for biomedical and soft tissue applications. The goal of this study was to investigate the effect of the experimental parameters on mechanical properties of PEUUs following exposure to different degrading environments, similar to that of the human body, using linear regression, producing one predictive model. The model utilizes two independent variables of poly(caprolactone) (PCL) type and copolymer crystallinity to predict the dependent variable of maximum tangential modulus (MTM). Results indicate that comparisons between PCLs at different degradation states are statistically different ( p < 0.0003), while the difference between experimental and predicted average MTM is statistically negligible ( p < 0.02). The linear correlation between experimental and predicted MTM values is R2 = 0.75. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3382-3387, 2013. [ABSTRACT FROM AUTHOR]

AAA is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the ApoE-/- AngII mouse model of aneurysm during disease progression. Adult ApoE-/- AngII infused mice along with wild-type controls were taken at 14 and 28 d. Aortas were excised and tested simultaneously for biaxial mechanical response and ECM organization. Data sets were it to a fung-type constitutive model to give peak strains and stiffness values. Images from two photon microscopy were quantified in order to assess the preferred fiber alignment and degree of fiber orientation. Biomechanical results found significant differences that were present at 14 d had returned to normal by 28 d along with significant changes in fiber orientation and dispersion indicating remodeling occurring within the aneurysmal wall. This return of some of the normal biomechanical function, in addition the continuing changes that occur in the microstructure suggest a restorative response that occurs in the ApoE-/- AngII infused model after the initial aneurysm formation. [ABSTRACT FROM AUTHOR]

The biomechanical response of tissues serves as a valuable marker in the prediction of disease and in understanding the related behavior of the body under various disease and age states. Alterations in the macroscopic biomechanical response of diseased tissues are well documented; however, a thorough understanding of the microstructural events that lead to these changes is poorly understood. In this article we introduce a novel microbiaxial optomechanical device that allows two-photon imaging techniques to be coupled with macromechanical stimulation in hydrated planar tissue specimens. This allows that the mechanical response of the microstructure can be quantified and related to the macroscopic response of the same tissue sample. This occurs without the need to fix tissue in strain states that could introduce a change in the microstructural configuration. We demonstrate the passive realignment of fibrous proteins under various types of loading, which demonstrates the ability of tissue microstructure to reinforce itself in periods of high stress. In addition, the collagen and elastin response of tissue during viscoelastic behavior is reported showing interstitial fluid movement and fiber realignment potentially responsible for the temporal behavior. We also demonstrate that nonhomogeneities in fiber strain exist over biaxial regions of assumed homogeneity. [ABSTRACT FROM AUTHOR]

The purpose of the current investigation was to use finite element analysis to quantify the complete strain field for the membranes of the FlexercellTM apparatus, a device extensively used to study the effects of mechanical loading on cultured cells. Four vacuum pressure simulations were run for the membrane for both the uniaxial and biaxial loading post, yielding the distribution of longitudinal (Exx) and transverse (Eyy) strain for the uniaxial post, and the radial (Err) and the circumferential (Eθθ) strain for the biaxial post. The discrete values of each strain were evaluated at the center of the loading post as well as the region off of the post. Experimental measurements were made for both types of loading posts in order to validate our simulations. The biaxial post simulation was found to provide a central circular region of equal and constant Err and Eθθ in the membrane on the post. Likewise, the uniaxial post simulation provided a definitive region of constant Exx for a central rectangular region on the post. For the uniaxial simulation, the region on the post resulted in small compressive Eyy, while the region off the post resulted in tensile Eyy. The biaxial simulation resulted in large tensile Err and Eθθ on the post, while the region off the post resulted in large Err and smaller Eθθ. Our simulations were reasonably consistent with the experimental measurements made for both types of loading posts. We believe that the results of this study will allow scientists to more accurately describe the response of cells to known strains on all portions of the membrane, thus increasing the range of known strain regions for investigation in the FlexercellTM apparatus. [Copyright &y& Elsevier]

Tissue engineering has gained attention as an alternative approach for developing small diameter tissue-engineered vascular grafts intended for bypass surgery, as an option to treat coronary heart disease. To promote the formation of a healthy endothelial cell monolayer in the lumen of the graft, polycaprolactone/gelatin/fibrinogen scaffolds were developed, and the surface was modified using thermoforming and coating with collagen IV and fibronectin. Human cord blood-derived endothelial cells (hCB-ECs) were seeded onto the scaffolds and the important characteristics of a healthy endothelial cell layer were evaluated under static conditions using human umbilical vein endothelial cells as a control. We found that polycaprolactone/gelatin/fibrinogen scaffolds that were thermoformed and coated are the most suitable for endothelial cell growth. hCB-ECs can proliferate, produce endothelial nitric oxide synthase, respond to interleukin 1 beta, and reduce platelet deposition. [ABSTRACT FROM AUTHOR]

A main goal of tissue engineering is the development of scaffolds that replace, restore and improve injured tissue. These scaffolds have to mimic natural tissue, constituted by an extracellular matrix (ECM) support, cells attached to the ECM, and signaling molecules such as growth factors that regulate cell function. In this study we created electrospun flat sheet scaffolds using different compositions of gelatin and fibrinogen. Smooth muscle cells (SMCs) were seeded on the scaffolds, and proliferation and infiltration were evaluated. Additionally, different concentrations of Transforming Growth Factor-beta2 (TGFβ2) were added to the medium with the aim of elucidating its effect on cell proliferation, migration and collagen production. Our results demonstrated that a scaffold with a composition of 80% gelatin-20% fibrinogen is suitable for tissue engineering applications since it promotes cell growth and migration. The addition of TGFβ2 at low concentrations (≤1 ng/ml) to the culture medium resulted in an increase in SMC proliferation and scaffold infiltration, and in the reduction of collagen production. In contrast, TGFβ2 at concentrations >1 ng/ml inhibited cell proliferation and migration while stimulating collagen production. According to our results TGFβ2 concentration has a differential effect on SMC function and thus can be used as a biochemical modulator that can be beneficial for tissue engineering applications. [ABSTRACT FROM AUTHOR]