Physiological Pressure Range Research Articles

Influence of different pressure regimes on the properties of an engineered small-diameter vascular scaffold tested in a custom-made bioreactor.

Vascular tissue engineering endeavors to design, fabricate, and validate biodegradable and bioabsorbable small-diameter vascular scaffolds engineered with bioactive molecules, capable of meeting the challenges imposed by commercial vascular prostheses. A comprehensive investigation of these engineered scaffolds in bioreactor is deemed essential as a prerequisite before any in vivo experimentation in order to get information regarding their behavior under physiological conditions and predict the biological activities they will possess. This study focuses on an innovative electrospun scaffold made of poly(caprolactone) and poly(glycerol sebacate), integrating quercetin, able to modulate inflammation, and gelatin, necessary to reduce permeability. A custom-made bioreactor was used to assess the performances of the scaffolds maintained under different pressure regimes, covering the human physiological pressure range. As results, the 3D microfibrous architecture was notably influenced by the release of bioactives, maintaining the adequate properties needed for the in vivo regeneration and scaffolds showed mechanical properties similar to human native artery. Release of gelatin was adequate to avoid blood leakage and useful to make the material porous during the testing period, whereas the amount of released quercetin was useful to counteract the post-surgery inflammation. This study showcases the successful validation of an engineered scaffold in a bioreactor, enabling to consider it as a promising candidate for vascular substitutes in in vivo applications. Our approach represents a significant leap forward in the field of vascular tissue engineering, offering a multifaceted solution to the complex challenges associated with small-diameter vascular prostheses.&#xD.

Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.

Ca2+ signalling plays a crucial role in determining lymphatic muscle cell excitability and contractility through its interaction with the Ca2+-activated Cl- channel anoctamin 1 (ANO1). In contrast, the large-conductance (BK) Ca2+-activated K+ channel (KCa) and other KCa channels have prominent vasodilatory actions by hyperpolarizing vascular smooth muscle cells. Here, we assessed the expression and contribution of the KCa family to mouse and rat lymphatic collecting vessel contractile function. The BK channel was the only KCa channel consistently expressed in fluorescence-activated cell sorting-purified mouse lymphatic muscle cell lymphatic muscle cells. We used a pharmacological inhibitor of BK channels, iberiotoxin, and small-conductance Ca2+-activated K+ channels, apamin, to inhibit KCa channels acutely in ex vivo isobaric myography experiments and intracellular membrane potential recordings. In basal conditions, BK channel inhibition had little to no effect on either mouse inguinal-axillary lymphatic vessel (MIALV) or rat mesenteric lymphatic vessel contractions or action potentials (APs). We also tested BK channel inhibition under loss of ANO1 either by genetic ablation (Myh11CreERT2-Ano1 fl/fl, Ano1ismKO) or by pharmacological inhibition with Ani9. In both Ano1ismKO MIALVs and Ani9-pretreated MIALVs, inhibition of BK channels increased contraction amplitude, increased peak AP and broadened the peak of the AP spike. In rat mesenteric lymphatic vessels, BK channel inhibition also abolished the characteristic post-spike notch, which was exaggerated with ANO1 inhibition, and significantly increased the peak potential and broadened the AP spike. We conclude that BK channels are present and functional on mouse and rat lymphatic muscle cells but are otherwise masked by the dominance of ANO1. KEY POINTS: Mouse and rat lymphatic muscle cells express functional BK channels. BK channels make little contribution to either rat or mouse lymphatic collecting vessel contractile function in basal conditions across a physiological pressure range. ANO1 limits the peak membrane potential achieved in the action potential and sets a plateau potential limiting the voltage-dependent activation of BK. BK channels are activated when ANO1 is absent or blocked and slightly impair contractile strength by reducing the peak membrane potential achieved in the action potential spike and accelerating the post-spike repolarization.

Interaction of material- and structural elasticity – an approach towards a physiological compliance in small-caliber vascular grafts

Research purpose: The low patency rate (less than 50% at a 5-years follow-up) of commercial vascular grafts is strongly associated with compliance mismatch between graft und native artery. To address this deficit, we investigated the influence of the material and structural elasticity on the compliance behavior of small caliber vascular graft gaining for a stress-strain behavior adapted to the native vessel. Material & Methods: By combining different thermoplastic polycarbonate urethanes (TPU) fibers with different elasticity and non-elastic polyvinylidene fluoride (PVDF) fibers in different warp knitted tubular textile structures, we incorporate material and structural elasticity in a vascular graft (I.D. < 6 mm). The evaluation of the tubular fabrics is performed by determining the compliance properties in a mean pressure range between 20 and 120 mmHg by tensile testing. Results: We identified the draw ration of the TPU fiber production, the stitch course density of the fabric and the thread tension of the TPU yarn during the warp knitting process as statistically highly significant effects ( p < .005) on the compliance. With an adapted setting of those parameters, we were able to improve the compliance of the textile vascular grafts over the entire physiological pressure range (20–120 mmHg) by 400–630 % compared to current clinical ePTFE (expanded polytetrafluoroethylene) grafts towards native vessels. Conclusion: By combining material and structural elasticity in a warp knitted textile structure, we were able to biomimic the compliance towards physiological properties. Our approach can be seen as blueprint to adapt elasticity properties in other implant applications.

Characterizing atherosclerotic tissues: in silico analysis of mechanical properties using intravascular ultrasound and inverse finite element methods.

Atherosclerosis is a prevalent cause of acute coronary syndromes that consists of lipid deposition inside the artery wall, creating an atherosclerotic plaque. Early detection may prevent the risk of plaque rupture. Nowadays, intravascular ultrasound (IVUS) is the most common medical imaging technology for atherosclerotic plaque detection. It provides an image of the section of the coronary wall and, in combination with new techniques, can estimate the displacement or strain fields. From these magnitudes and by inverse analysis, it is possible to estimate the mechanical properties of the plaque tissues and their stress distribution. In this paper, we presented a methodology based on two approaches to characterize the mechanical properties of atherosclerotic tissues. The first approach estimated the linear behavior under particular pressure. In contrast, the second technique yielded the non-linear hyperelastic material curves for the fibrotic tissues across the complete physiological pressure range. To establish and validate this method, the theoretical framework employed in silico models to simulate atherosclerotic plaques and their IVUS data. We analyzed different materials and real geometries with finite element (FE) models. After the segmentation of the fibrotic, calcification, and lipid tissues, an inverse FE analysis was performed to estimate the mechanical response of the tissues. Both approaches employed an optimization process to obtain the mechanical properties by minimizing the error between the radial strains obtained from the simulated IVUS and those achieved in each iteration. The second methodology was successfully applied to five distinct real geometries and four different fibrotic tissues, getting median R 2 of 0.97 and 0.92, respectively, when comparing the real and estimated behavior curves. In addition, the last technique reduced errors in the estimated plaque strain field by more than 20% during the optimization process, compared to the former approach. The findings enabled the estimation of the stress field over the hyperelastic plaque tissues, providing valuable insights into its risk of rupture.

Enhancing decellularized vascular scaffolds with PVDF and PCL reinforcement: a fused deposition modeling approach

BackgroundDecellularized xenogenic scaffolds represent a promising substrate for tissue-engineered vascular prostheses, particularly those with smaller diameters (<6 mm). Despite their benefits, a notable limitation presents itself during decellularization, namely, the diminished mechanical strength that introduces the risk of aneurysmal dilations in the early post-implantation period. This study introduces a strategy for modification the mechanical properties of these biological scaffolds through the forming of an external polymeric reinforcement via thermal extrusion.MethodsThe study utilized scaffolds fabricated from bovine internal mammary arteries through decellularization and preservation. The scaffolds were divided into subgroups and reinforced with polymeric helices made of Polyvinylidene fluoride (PVDF) and Polycaprolactone (PCL), n = 5 for each. An experimental setup for external reinforcement coating was designed. Computed microtomography was employed to obtain accurate 3D models of the scaffolds. Mechanical properties were evaluated through in vitro uniaxial tension tests (Z50, Zwick/Roell, Germany), compliance evaluation and numerical simulations (Abaqus/CAE, Dassault Systemes, France) to investigate the effect of external reinforcement on aneurysm growth.ResultsUsing a double-layer helix for the reinforcement significantly enhanced the radial tensile strength of the scaffolds, increasing it up to 2.26 times. Yet, the comparison of vessel's compliance between two reinforced and the Control scaffolds within the physiological pressures range did not reveal any significant differences. Numerical simulation of aneurysm growth showed that thin-walled regions of the Control scaffold developed aneurysmal-type protrusions, bulging up to 0.7 mm, with a substantial degradation of mechanical properties. In contrast, both PVDF and PCL reinforced scaffolds did not exhibit significant property degradation, with deformations ranging 0.1–0.13 mm depending on the model, and a maximum decrease in the modulus of elasticity of 23%.ConclusionThe results of the study demonstrated that the external polymer helical reinforcement of decellularized scaffolds via thermal extrusion enables a controlled modification of mechanical properties, notably enhancing radial strength while maintaining sufficient compliance within the physiological pressure range. A series of in vitro tests demonstrated the consistency and potential of this approach for decellularized xenogenic scaffolds, a concept that had not been explored before.

"In Vitro" Evaluation of Energy-Based Sealing of Graft Side Branches in Bypass Surgery.

Our objective was to compare the in vitro efficacy of electrothermal bipolar [EB] vessel sealing and ultrasonic harmonic scalpel [HS] versus mechanical interruption, with conventional ties or surgical clips (SC), in sealing saphenous vein (SV) collaterals, during its eventual preparation for bypass surgery. Experimental in vitro study on 30 segments of SV. Each fragment included two collaterals at least 2mm in diameter. One of them was sealed by ligation with 3/0 silk ties (control) and the other one with EB (n = 10), HS (n = 10) or medium-6mm SC (n = 10). After incorporation in a closed circuit with pulsatile flow, the pressure was progressively increased until causing rupture. Collateral diameter, burst pressure, leak point, and histological study were recorded. Burst pressure was higher for SC (1320.20 ± 373.847mmHg) as compared with EB (942.2 ± 344.9mmHg, p = 0.065), and especially with HS (637.00 ± 320.61mmHg, p = 0.0001). No statistically significant difference between EB and HS was found, and bursting always happened at supraphysiological pressures. The leak point for HS was always detected in the sealing zone (10/10), while for EB and SC, it occurred in the sealing zone only in 6/10(60%) and 4/10(40%), respectively (p = 0.015). Energy delivery devices showed similar efficacy and safety in sealing of SV side branches. Although bursting pressure was lower than with tie ligature or SC, non-inferiority efficacy was shown at the range of physiological pressures in both, EB and HS. Due to their speed and easy handling, they may be useful in the preparation of the venous graft during revascularization surgery. However, remaining questions about healing process, potential spread of tissue damage and sealing durability, will require further analysis.

Real-Time Monitoring Platform for Ocular Drug Delivery.

Real-time measurement is important in modern dissolution testing to aid in parallel drug characterisation and quality control (QC). The development of a real-time monitoring platform (microfluidic system, a novel eye movement platform with temperature sensors and accelerometers and a concentration probe setup) in conjunction with an in vitro model of the human eye (PK-Eye™) is reported. The importance of surface membrane permeability when modelling the PK-Eye™ was determined with a "pursing model" (a simplified setup of the hyaloid membrane). Parallel microfluidic control of PK-Eye™ models from a single source of pressure was performed with a ratio of 1:6 (pressure source:models) demonstrating scalability and reproducibility of pressure-flow data. Pore size and exposed surface area helped obtain a physiological range of intraocular pressure (IOP) within the models, demonstrating the need to reproduce in vitro dimensions as closely as possible to the real eye. Variation of aqueous humour flow rate throughout the day was demonstrated with a developed circadian rhythm program. Capabilities of different eye movements were programmed and achieved with an in-house eye movement platform. A concentration probe recorded the real-time concentration monitoring of injected albumin-conjugated Alexa Fluor 488 (Alexa albumin), which displayed constant release profiles. These results demonstrate the possibility of real-time monitoring of a pharmaceutical model for preclinical testing of ocular formulations.

Lymphatic contractile dysfunction in mouse models of Cantú Syndrome with KATP channel gain-of-function.

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of KATP channels. KATP overactivity results in a chronic reduction in arterial tone and hypotension, leading to other systemic cardiovascular complications. However, the underlying mechanism of lymphedema, developed by>50% of CS patients, is unknown. We investigated whether lymphatic contractile dysfunction occurs in mice expressing CS mutations in Kir6.1 (Kir6.1[V65M]) or SUR2 (SUR2[A478V], SUR2[R1154Q]). Pressure myograph tests of contractile function of popliteal lymphatic vessels over the physiological pressure range revealed significantly impaired contractile strength and reduced frequency of spontaneous contractions at all pressures in heterozygous Kir6.1[V65M] vessels, compared to control littermates. Contractile dysfunction of intact popliteal lymphatics in vivo was confirmed using near-infrared fluorescence microscopy. Homozygous SUR2[A478V] vessels exhibited profound contractile dysfunction ex vivo, but heterozygous SUR2[A478V] vessels showed essentially normal contractile function. However, further investigation of vessels from all three GoF mouse strains revealed significant disruption in contraction wave entrainment, decreased conduction speed and distance, multiple pacemaker sites, and reversing wave direction. Tests of 2-valve lymphatic vessels forced to pump against an adverse pressure gradient revealed that all CS-associated genotypes were essentially incapable of pumping under an imposed outflow load. Our results show that varying degrees of lymphatic contractile dysfunction occur in proportion to the degree of molecular GoF in Kir6.1 or SUR2. This is the first example of lymphatic contractile dysfunction caused by a smooth muscle ion channel mutation and potentially explains the susceptibility of CS patients to lymphedema.

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results.

BackgroundExisting working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control.MethodsSix ∼70 kg pig hearts were evaluated in vivo, then ex vivo in left‐ventricular working mode using the presented afterload. Both in vivo and ex vivo, the hearts were evaluated at two exertion levels: at rest and following a 20 μg adrenaline bolus, while measuring aortic pressure and flow, left ventricular pressure and volume, and left atrial pressure.ResultsThe afterload gave aortic pressure waveforms that matched the general shape of the in vivo measurements. A wide range of physiological systolic pressures (93 to 160 mm Hg) and diastolic pressures (73 to 113 mm Hg) were generated by the afterload.ConclusionsWith the presented afterload concept, multiple physiological loading conditions could be tested ex vivo, and compared with the corresponding in vivo data. An additional control loop from the set pressure limits to the measured systolic and diastolic aortic pressure is proposed to address discrepancies observed between the set limits and the measured pressures.

The Role of Layer-Specific Residual Stresses in Arterial Mechanics: Analysis via a Novel Modelling Framework

The existence of residual stresses in unloaded arteries has long been known. However, their effect is often neglected in experimental studies. Using a recently developed modelling framework, we aimed to investigate the role of residual stresses in the mechanical behaviour of the tri-layered wall of the pig thoracic aorta. The mechanical behaviour of the intact wall and isolated layers of n = 3 pig thoracic aortas was investigated via uniaxial tensile testing. After modelling the layer-specific mechanical data using a hyperelastic strain energy function, the layer-specific deformations in the unloaded vessel were estimated so that the mechanical response of the computationally assembled tri-layered flat wall would match that measured experimentally. Physiological tension–inflation of the cylindrical tri-layered vessel was then simulated, analysing changes in the distribution of stresses in the three layers when neglecting residual stresses. In the tri-layered model with residual stresses, layers exhibited comparable stresses throughout the physiological range of pressure. At 100 mmHg, intimal, medial, and adventitial circumferential load bearings were 16 pm 3%, 59 pm 4%, and 25 pm 2%, respectively. Adventitial stiffening at high pressures produced a shift in load bearing from the media to the adventitia. When neglecting residual stresses, in vivo stresses were highest at the intima and lowest at the adventitia. Consequently, the intimal and adventitial load bearings, 23 pm 2% and 18 pm 3% at 100 mmHg, were comparable at all pressures. Residual stresses play a crucial role in arterial mechanics guaranteeing a uniform distribution of stresses through the wall thickness. Neglecting these leads to incorrect interpretation of the layers’ role in arterial mechanics.

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations.

Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure-volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure-volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.

Five years of cardio-ankle vascular index (CAVI) and CAVI0: how close are we to a pressure-independent index of arterial stiffness?

Pulse wave velocity, a common metric of arterial stiffness, is an established predictor for cardiovascular events and mortality. However, its intrinsic pressure-dependency complicates the discrimination of acute and chronic impacts of increased blood pressure on arterial stiffness. Cardio-ankle vascular index (CAVI) represented a significant step towards the development of a pressure-independent arterial stiffness metric. However, some potential limitations of CAVI might render this arterial stiffness metric less pressure-independent than originally thought. For this reason, we later introduced CAVI0. Nevertheless, advantages of one approach over the other are left debated. This review aims to shed light on the pressure (in)dependency of both CAVI and CAVI0. By critically reviewing results from studies reporting both CAVI and CAVI0 and using simple analytical methods, we show that CAVI0 may enhance the pressure-independent assessment of arterial stiffness, especially in the presence of large inter-individual differences in blood pressure.

Bio-composites reinforced with unique coral collagen fibers: Towards biomimetic-based small diameter vascular grafts

Cardiovascular Diseases (CVDs) are the leading cause of death worldwide. Approximately 31% of all global deaths are caused by CVDs, of which 42% are attributable to coronary artery disease (CAD). CAD is characterized by a narrowing of arteries that restricts the normal blood flow. Over time, surgical intervention is required in severe cases of occlusions and includes implantation of autologous vessels. Today synthetic grafts are used successfully as replacements for blood vessels with a diameter larger than 6 mm. However, they often fail as small-diameter blood vessel replacements.This study introduces a new biocomposite material system consisting of unique and long (cm-scale) collagen fibers derived from soft corals embedded within an alginate hydrogel matrix. The new biocomposite layers were used to fabricate grafts, towards developing a new class of tissue-engineered small-diameter blood vessels. These constructs consisted of both circumferentially and longitudinally oriented collagen fibers. The mechanical properties of the grafts were investigated via a new experimental setup constructed in our lab for this purpose, which applied internal pressure levels of 0–300 mmHg. Similar to native coronary arteries, the biocomposite tubes demonstrated a compliance of 4.88 ± 0.99%/100 mmHg for a physiologic pressure range of 80–120 mmHg. Furthermore, a numerical finite element simulation model is proposed to generate the overall mechanical response of the construct. It is composed of axial and circumferential fibers embedded within the continuum alginate elements. Good prediction is demonstrated when compared with the measured pressure-strain response. Moreover, we examined biocompatibility and cell growth on the collagen fibers. Fibroblast cells proliferated during the experiment that lasted for 32 days and showed aligned configuration with the collagen fiber orientation.The novelty of this study is manifested in the use of naturally derived coral-based long collagen fibers for the development of a new class of tissue-engineered grafts. The proposed novel biocomposite graft demonstrated both mechanical and biological compatibility and can be further developed for small-diameter blood-vessel replacement.

Electrospinning of small diameter vascular grafts with preferential fiber directions and comparison of their mechanical behavior with native rat aortas

Conventional electrospun small diameter vascular grafts have a random fiber orientation. In order to achieve mechanical characteristics similar to a native blood vessel, a controllable fiber orientation is of interest. In this study the electrospinning jet was directly controlled by means of an auxiliary, changeable electrostatic field, so that the fibers could be deposited in adjustable orientations. Prostheses with circumferentially, axially, fenestrated and randomly aligned fibers were electrospun on Ø2mm mandrels out of a thermoplastic polyurethane (PUR) and a polylactid acid (PLLA). The impact of the materials and the various preferential fiber orientations on the resulting biomechanics was investigated and compared with that of the native rat aorta in quasistatic and dynamic hoop tensile tests. The test protocol included 3000 dynamic loading cycles in the physiological blood pressure range and ended with a quasistatic tensile test. Any orientation of the fibers in a particular direction resulted in a significant reduction in scaffold porosity for both materials. The standard randomly oriented PUR grafts showed the highest compliance of 29.7 ± 5.5 [%/100 mmHg] and were thus closest to the compliance of the rat aortas, which was 37.2 ± 6.5 [%/100 mmHg]. The maximum tensile force was increased at least 6 times compared to randomly spun grafts by orienting the fibers in the circumferential direction. During the 3000 loading cycles, creeping of the native rat aorta was below 1% whereas the electrospun grafts showed creeping up to 2.4 ± 1.2%. Although the preferred fiber orientations were only partially visible in the scanning electron micrographs, the mechanical effects were evident. The investigations suggest a multi-layer wall structure of the vascular prosthesis, since none of the preferred fiber directions and the materials used could imitate the typical j-shaped mechanical characteristics of the rat aorta.

Development of an FEA framework for analysis of subject-specific aortic compliance based on 4D flow MRI

This paper presents a subject-specific in-silico framework in which we uncover the relationship between the spatially varying constituents of the aorta and the non-linear compliance of the vessel during the cardiac cycle uncovered through our MRI investigations. A microstructurally motivated constitutive model is developed, and simulations reveal that internal vessel contractility, due to pre-stretched elastin and actively generated smooth muscle cell stress, must be incorporated, along with collagen strain stiffening, in order to accurately predict the non-linear pressure-area relationship observed in-vivo. Modelling of elastin and smooth muscle cell contractility allows for the identification of the reference vessel configuration at zero-lumen pressure, in addition to accurately predicting high- and low-compliance regimes under a physiological range of pressures. This modelling approach is also shown to capture the key features of elastin digestion and SMC activation experiments. The volume fractions of the constituent components of the aortic material model were computed so that the in-silico pressure-area curves accurately predict the corresponding MRI data at each location. Simulations reveal that collagen and smooth muscle volume fractions increase distally, while elastin volume fraction decreases distally, consistent with reported histological data. Furthermore, the strain at which collagen transitions from low to high stiffness is lower in the abdominal aorta, again supporting the histological finding that collagen waviness is lower distally. The analyses presented in this paper provide new insights into the heterogeneous structure-function relationship that underlies aortic biomechanics. Furthermore, this subject-specific MRI/FEA methodology provides a foundation for personalised in-silico clinical analysis and tailored aortic device development. Statement of significanceThis study provides a significant advance in in-silico medicine by capturing the structure/function relationship of the subject-specific human aorta presented in our previous MRI analyses. A physiologically based aortic constitutive model is developed, and simulations reveal that internal vessel contractility must be incorporated, along with collagen strain stiffening, to accurately predict the in-vivo non-linear pressure-area relationship. Furthermore, this is the first subject-specific model to predict spatial variation in the volume fractions of aortic wall constituents. Previous studies perform phenomenological hyperelastic curve fits to medical imaging data and ignore the prestress contribution of elastin, collagen, and SMCs and the associated zero-pressure reference state of the vessel. This novel MRI/FEA framework can be used as an in-silico diagnostic tool for the early stage detection of aortic pathologies.

A novel polymeric fibrous microstructured biodegradable small-caliber tubular scaffold for cardiovascular tissue engineering

Increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop artificial small-caliber cardiovascular grafts for surgical intervention of diseased natural arteries, as alternatives to the gold standard autologous implants. Synthetic small-caliber grafts are still not in use due to increased risk of restenosis, lack of lumen re-endothelialization and mechanical mismatch, leading sometimes either to graft failure or to unsuccessful remodeling and pathology of the distal parts of the anastomosed healthy vascular tissues. In this work, we aimed to synthesize small-caliber polymeric (polycaprolactone) tissue-engineered vascular scaffolds that mimic the structure and biomechanics of natural vessels. Electrospinning was implemented to prepare microstructured polymeric membranes with controlled axis-parallel fiber alignment. Consequently, we designed small-caliber multilayer anisotropic biodegradable nanofibrous tubular scaffolds, giving attention to their radial compliance. Polycaprolactone scaffold morphology and mechanical properties were assessed, quantified, and compared with those of native vessels and commercial synthetic grafts. Results showed a highly hydrophobic scaffold material with a three-layered tubular morphology, 4-mm internal diameter/0.25 ± 0.09-mm thickness, consisting of predominantly axially aligned thin (1.156 ± 0.447 μm), homogeneous and continuous microfibers, with adequate (17.702 ± 5.369 μm) pore size, potentially able to promote cell infiltration in vivo. In vitro accelerated degradation showed a 5% mass loss within 17–25 weeks. Mechanical anisotropy was attained as a result, almost one order of magnitude difference of the elastic modulus (18 ± 3 MPa axially/1 ± 0.3 MPa circumferentially), like that of natural arterial walls. Furthermore, a desirable radial compliance (5.04 ± 0.82%, within the physiological pressure range) as well as cyclic stability of the tubular scaffold was achieved. Finally, cytotoxicity evaluation of the polymeric scaffolds revealed that the materials were nontoxic and did not release substances harmful to living cells (over 80% cell viability achieved).

Estimating aortic thoracic aneurysm rupture risk using tension-strain data in physiological pressure range: an in vitro study.

Previous studies have shown that the rupture properties of an ascending thoracic aortic aneurysm (ATAA) are strongly correlated with the pre-rupture response features. In this work, we present a two-step machine learning method to predict where the rupture is likely to occur in ATAA and what safety reserve the structure may have. The study was carried out using ATAA specimens from 15 patients who underwent surgical intervention. Through inflation test, full-field deformation data and post-rupture images were collected, from which the wall tension and surface strain distributions were computed. The tension-strain data in the pressure range of 9-18kPa were fitted to a third-order polynomial to characterize the response properties. It is hypothesized that the region where rupture is prone to initiate is associated with a high level of tension buildup. A machine learning method is devised to predict the peak risk region. The predicted regions were found to match the actual rupture sites in 13 samples out of the total 15. In the second step, another machine learning model is utilized to predict the tissue's rupture strength in the peak risk region. Results suggest that the ATAA rupture risk can be reasonably predicted using tension-strain response in the physiological range. This may open a pathway for evaluating the ATAA rupture propensity using information of in vivo response.

Portable Oxygen-Sensing Device for the Improved Assessment of Compartment Syndrome and other Hypoxia-Related Conditions.

Measurement of intramuscular oxygen could play a key role in the early diagnosis of acute compartment syndrome, a common condition occurring after severe trauma leading to ischemia and long-term consequences including rhabdomyolysis, limb loss, and death. However, to date, there is no existing oxygen sensor approved for such a purpose. To address the need to improve the assessment of compartment syndrome, a portable fiber-optic device for intramuscular oxygen measurements was developed. The device is based on phosphorescence quenching, where the tip of an optical fiber was coated with a poly(propyl methacrylate) (PPMA) matrix containing a brightly emitting Pt(II)-core porphyrin. The optoelectronic circuit is highly portable and is based on a microspectrometer and a microcontroller readout with a smartphone. Results from an in vivo tourniquet porcine model show that the sensor is sensitive across the physiological oxygen partial pressure range of 0-80 mmHg and exhibits an appropriate and reproducible response to changes in intramuscular oxygen. A commercial laboratory oxygen sensor based on a lifetime measurement did not respond as expected.

An interferometric ex vivo study of corneal biomechanics under physiologically representative loading, highlighting the role of the limbus in pressure compensation

BackgroundThe mechanical properties of the cornea are complex and regionally variable. This paper uses an original method to investigate the biomechanics of the cornea in response to hydrostatic loading over the typical physiological range of intra-ocular pressure (IOP) fluctuations thereby increasing understanding of clinically relevant corneal biomechanical properties and their contributions to the refractive properties of the cornea.MethodsDisplacement speckle pattern interferometry (DSPI) was used to measure the total surface displacement of 40 porcine and 6 human corneal-scleral specimens in response to pressure variations up to 1 mmHg from a baseline of 16.5 mmHg. All specimens were mounted in a modified artificial anterior chamber (AAC) and loaded hydrostatically. Areas of high strain in response to loading were identified by comparing the displacements across different regions.ResultsThe nature of the response of the corneal surface to loading demonstrated high regional topographic variation. Mechanical properties were shown to be asymmetrical, and deformation of the limbal and pre-limbal regions dominated these responses respectively with over 90% (N-T) and 60% (S-I) of the total maximum displacement occurring in these regions indicating high-strain. In contrast, the curvature of the central cornea remained relatively unchanged merely translating in position.ConclusionsThe limbal and pre-limbal regions of the cornea appear to be fundamental to the absorption of small pressure fluctuations facilitating the curvature of the central cornea to remain relatively unchanged. The differential mechanical properties of this region could have important implications for the application of corneal surgery and corneal crosslinking, warranting further investigation.

Modeling intracranial aneurysm stability and growth: an integrative mechanobiological framework for clinical cases

We present a novel patient-specific fluid-solid-growth framework to model the mechanobiological state of clinically detected intracranial aneurysms (IAs) and their evolution. The artery and IA sac are modeled as thick-walled, non-linear elastic fiber-reinforced composites. We represent the undulation distribution of collagen fibers: the adventitia of the healthy artery is modeled as a protective sheath whereas the aneurysm sac is modeled to bear load within physiological range of pressures. Initially, we assume the detected IA is stable and then consider two flow-related mechanisms to drive enlargement: (1) low wall shear stress; (2) dysfunctional endothelium which is associated with regions of high oscillatory flow. Localized collagen degradation and remodelling gives rise to formation of secondary blebs on the aneurysm dome. Restabilization of blebs is achieved by remodelling of the homeostatic collagen fiber stretch distribution. This integrative mechanobiological modelling workflow provides a step towards a personalized risk-assessment and treatment of clinically detected IAs.