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  1. Lim E, Salamonsen RF, Mansouri M, Gaddum N, Mason DG, Timms DL, et al.
    Artif Organs, 2015 Feb;39(2):E24-35.
    PMID: 25345482 DOI: 10.1111/aor.12370
    The present study investigates the response of implantable rotary blood pump (IRBP)-assisted patients to exercise and head-up tilt (HUT), as well as the effect of alterations in the model parameter values on this response, using validated numerical models. Furthermore, we comparatively evaluate the performance of a number of previously proposed physiologically responsive controllers, including constant speed, constant flow pulsatility index (PI), constant average pressure difference between the aorta and the left atrium, constant average differential pump pressure, constant ratio between mean pump flow and pump flow pulsatility (ratioP I or linear Starling-like control), as well as constant left atrial pressure ( P l a ¯ ) control, with regard to their ability to increase cardiac output during exercise while maintaining circulatory stability upon HUT. Although native cardiac output increases automatically during exercise, increasing pump speed was able to further improve total cardiac output and reduce elevated filling pressures. At the same time, reduced venous return associated with upright posture was not shown to induce left ventricular (LV) suction. Although P l a ¯ control outperformed other control modes in its ability to increase cardiac output during exercise, it caused a fall in the mean arterial pressure upon HUT, which may cause postural hypotension or patient discomfort. To the contrary, maintaining constant average pressure difference between the aorta and the left atrium demonstrated superior performance in both exercise and HUT scenarios. Due to their strong dependence on the pump operating point, PI and ratioPI control performed poorly during exercise and HUT. Our simulation results also highlighted the importance of the baroreflex mechanism in determining the response of the IRBP-assisted patients to exercise and postural changes, where desensitized reflex response attenuated the percentage increase in cardiac output during exercise and substantially reduced the arterial pressure upon HUT.
  2. Oshkour AA, Talebi H, Seyed Shirazi SF, Yau YH, Tarlochan F, Abu Osman NA
    Artif Organs, 2015 Feb;39(2):156-64.
    PMID: 24841371 DOI: 10.1111/aor.12315
    This study aimed to assess the performance of different longitudinal functionally graded femoral prostheses. This study was also designed to develop an appropriate prosthetic geometric design for longitudinal functionally graded materials. Three-dimensional models of the femur and prostheses were developed and analyzed. The elastic modulus of these prostheses in the sagittal plane was adjusted along a gradient direction from the distal end to the proximal end. Furthermore, these prostheses were composed of titanium alloy and hydroxyapatite. Results revealed that strain energy, interface stress, and developed stress in the femoral prosthesis and the bone were influenced by prosthetic geometry and gradient index. In all of the prostheses with different geometries, strain energy increased as gradient index increased. Interface stress and developed stress decreased. The minimum principal stress and the maximum principal stress of the bone slightly increased as gradient index increased. Hence, the combination of the femoral prosthetic geometry and functionally graded materials can be employed to decrease stress shielding. Such a combination can also be utilized to achieve equilibrium in terms of the stress applied on the implanted femur constituents; thus, the lifespan of total hip replacement can be prolonged.
  3. Baharuddin MY, Salleh ShH, Suhasril AA, Zulkifly AH, Lee MH, Omar MA, et al.
    Artif Organs, 2014 Jul;38(7):603-8.
    PMID: 24404766 DOI: 10.1111/aor.12222
    Total hip arthroplasty is a flourishing orthopedic surgery, generating billions of dollars of revenue. The cost associated with the fabrication of implants has been increasing year by year, and this phenomenon has burdened the patient with extra charges. Consequently, this study will focus on designing an accurate implant via implementing the reverse engineering of three-dimensional morphological study based on a particular population. By using finite element analysis, this study will assist to predict the outcome and could become a useful tool for preclinical testing of newly designed implants. A prototype is then fabricated using 316L stainless steel by applying investment casting techniques that reduce manufacturing cost without jeopardizing implant quality. The finite element analysis showed that the maximum von Mises stress was 66.88 MPa proximally with a safety factor of 2.39 against endosteal fracture, and micromotion was 4.73 μm, which promotes osseointegration. This method offers a fabrication process of cementless femoral stems with lower cost, subsequently helping patients, particularly those from nondeveloped countries.
  4. Ooi HL, Ng SC, Lim E, Salamonsen RF, Avolio AP, Lovell NH
    Artif Organs, 2014 Mar;38(3):E57-67.
    PMID: 24422872 DOI: 10.1111/aor.12220
    In recent years, extensive studies have been conducted in the area of pumping state detection for implantable rotary blood pumps. However, limited studies have focused on automatically identifying the aortic valve non-opening (ANO) state despite its importance in the development of control algorithms aiming for myocardial recovery. In the present study, we investigated the performance of 14 ANO indices derived from the pump speed waveform using four different types of classifiers, including linear discriminant analysis, logistic regression, back propagation neural network, and k-nearest neighbors (KNN). Experimental measurements from four greyhounds, which take into consideration the variations in cardiac contractility, systemic vascular resistance, and total blood volume were used. By having only two indices, (i) the root mean square value, and (ii) the standard deviation, we were able to achieve an accuracy of 92.8% with the KNN classifier. Further increase of the number of indices to five for the KNN classifier increases the overall accuracy to 94.6%.
  5. Ng SC, Lim E, Mason DG, Avolio AP, Lovell NH
    Artif Organs, 2013 Aug;37(8):E145-54.
    PMID: 23635073 DOI: 10.1111/aor.12079
    In recent times, the problem of noninvasive suction detection for implantable rotary blood pumps has attracted substantial research interest. Here, we compare the performance of various suction indices for different types of suction and non-suction events based on pump speed irregularity. A total of 171 different indices that consist of previously proposed as well as newly introduced suction indices are tested using regularized logistic regression. These indices can be classified as amplitude based (derived from the mean, maximum, and minimum values of a cycle), duration based (derived from the duration of a cycle), gradient based (derived from the first order as well as higher order differences) and frequency based (derived from the power spectral density). The non-suction event data consists of ventricular ejection with or without arrhythmia and intermittent and continuous non-opening of the aortic valve. The suction event data consists of partial ventricular collapse that occurs intermittently as well as continuously with or without arrhythmia. In addition, we also attempted to minimize the usage of multiple indices by applying the sequential forward floating selection method to find which combination of indices gives the best performance. In general, the amplitude-based and gradient-based indices performed quite well while the duration-based and frequency-based indices performed poorly. By having only two indices ([i] the maximum gradient change in positive slope; and [ii] the standard deviation of the maximum value in a cycle), we were able to achieve a sensitivity of 98.9% and a specificity of 99.7%.
  6. Lim E, Dokos S, Salamonsen RF, Rosenfeldt FL, Ayre PJ, Lovell NH
    Artif Organs, 2012 May;36(5):E110-24.
    PMID: 22489799 DOI: 10.1111/j.1525-1594.2012.01449.x
    A heart-pump interaction model has been developed based on animal experimental measurements obtained with a rotary blood pump in situ. Five canine experiments were performed to investigate the interaction between the cardiovascular system and the implantable rotary blood pump over a wide range of operating conditions, including variations in cardiac contractility and heart rate, systemic vascular resistance (SVR), and total blood volume (V(total) ). It was observed in our experiments that SVR decreased with increasing mean pump speed under the healthy condition, but was relatively constant during the speed ramp study under reduced cardiac contractility conditions. Furthermore, we also found a significant increase in pulmonary vascular resistance with increasing mean pump speed and decreasing total blood volume, despite a relatively constant SVR. Least squares parameter estimation methods were utilized to fit a subset of model parameters in order to achieve better agreement with the experimental data and to evaluate the robustness and validity of the model under various operating conditions. The fitted model produced reasonable agreement with the experimental measurements, both in terms of mean values and steady-state waveforms. In addition, all the optimized parameters were within physiological limits.
  7. Lim E, Dokos S, Salamonsen RF, Rosenfeldt FL, Ayre PJ, Lovell NH
    Artif Organs, 2012 May;36(5):E125-37.
    PMID: 22489771 DOI: 10.1111/j.1525-1594.2012.01448.x
    Numerical models, able to simulate the response of the human cardiovascular system (CVS) in the presence of an implantable rotary blood pump (IRBP), have been widely used as a predictive tool to investigate the interaction between the CVS and the IRBP under various operating conditions. The present study investigates the effect of alterations in the model parameter values, that is, cardiac contractility, systemic vascular resistance, and total blood volume on the efficiency of rotary pump assistance, using an optimized dynamic heart-pump interaction model previously developed in our laboratory based on animal experimental measurements obtained from five canines. The effect of mean pump speed and the circulatory perturbations on left and right ventricular pressure volume loops, mean aortic pressure, mean cardiac output, pump assistance ratio, and pump flow pulsatility from both the greyhound experiments and model simulations are demonstrated. Furthermore, the applicability of some of the previously proposed control parameters, that is, pulsatility index (PI), gradient of PI with respect to pump speed, pump differential pressure, and aortic pressure are discussed based on our observations from experimental and simulation results. It was found that previously proposed control strategies were not able to perform well under highly varying circulatory conditions. Among these, control algorithms which rely on the left ventricular filling pressure appear to be the most robust as they emulate the Frank-Starling mechanism of the heart.
  8. Lim E, Alomari AH, Savkin AV, Dokos S, Fraser JF, Timms DL, et al.
    Artif Organs, 2011 Aug;35(8):E174-80.
    PMID: 21843286 DOI: 10.1111/j.1525-1594.2011.01268.x
    We propose a deadbeat controller for the control of pulsatile pump flow (Q(p) ) in an implantable rotary blood pump (IRBP). Noninvasive measurements of pump speed and current are used as inputs to a dynamical model of Q(p) estimation, previously developed and verified in our laboratory. The controller was tested using a lumped parameter model of the cardiovascular system (CVS), in combination with the stable dynamical models of Q(p) and differential pressure (head) estimation for the IRBP. The control algorithm was tested with both constant and sinusoidal reference Q(p) as input to the CVS model. Results showed that the controller was able to track the reference input with minimal error in the presence of model uncertainty. Furthermore, Q(p) was shown to settle to the desired reference value within a finite number of sampling periods. Our results also indicated that counterpulsation yields the minimum left ventricular stroke work, left ventricular end diastolic volume, and aortic pulse pressure, without significantly affecting mean cardiac output and aortic pressure.
  9. Braz GP, Russold MF, Fornusek C, Hamzaid NA, Smith RM, Davis GM
    Artif Organs, 2015 Oct;39(10):855-62.
    PMID: 26471136 DOI: 10.1111/aor.12619
    This is a case series study with the objective of comparing two motion sensor automated strategies to avert knee buckle during functional electrical stimulation (FES)-standing against a conventional hand-controlled (HC) FES approach. The research was conducted in a clinical exercise laboratory gymnasium at the University of Sydney, Australia. The automated strategies, Aut-A and Aut-B, applied fixed and variable changes of neurostimulation, respectively, in quadriceps amplitude to precisely control knee extension during standing. HC was an "on-demand" increase of stimulation amplitude to maintain stance. Finally, maximal FES amplitude (MA) was used as a control condition, whereby knee buckle was prevented by maximal isometric muscle recruitment. Four AIS-A paraplegics undertook 4 days of testing each, and each assessment day comprised three FES standing trials using the same strategy. Cardiorespiratory responses were recorded, and quadriceps muscle oxygenation was quantified using near-infrared spectroscopy. For all subjects, the longest standing times were observed during Aut-A, followed by Aut-B, and then HC and MA. The standing times of the automated strategies were superior to HC by 9-64%. Apart from a lower heart rates during standing (P = 0.034), the automation of knee extension did not promote different cardiorespiratory responses compared with HC. The standing times during MA were significantly shorter than during the automated or "on-demand" strategies (by 80-250%). In fact, the higher isometric-evoked quadriceps contraction during MA resulted in a greater oxygen demand (P 
  10. Salamonsen RF, Lim E, Moloney J, Lovell NH, Rosenfeldt FL
    Artif Organs, 2015 Aug;39(8):681-90.
    PMID: 26146861 DOI: 10.1111/aor.12550
    This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps.
  11. Darlis N, Osman K, Padzillah MH, Dillon J, Md Khudzari AZ
    Artif Organs, 2018 May;42(5):493-499.
    PMID: 29280161 DOI: 10.1111/aor.13021
    Physiologically, blood ejected from the left ventricle in systole exhibited spiral flow characteristics. This spiral flow has been proven to have several advantages such as lateral reduction of directed forces and thrombus formation, while it also appears to be clinically beneficial in suppressing neurological complications. In order to deliver spiral flow characteristics during cardiopulmonary bypass operation, several modifications have been made on an aortic cannula either at the internal or at the outflow tip; these modifications have proven to yield better hemodynamic performances compared to standard cannula. However, there is no modification done at the inlet part of the aortic cannula for inducing spiral flow so far. This study was carried out by attaching a spiral inducer at the inlet of an aortic cannula. Then, the hemodynamic performances of the new cannula were compared with the standard straight tip end-hole cannula. This is achieved by modeling the cannula and attaching the cannula at a patient-specific aorta model. Numerical approach was utilized to evaluate the hemodynamic performance, and a water jet impact experiment was used to demonstrate the jet force generated by the cannula. The new spiral flow aortic cannula has shown some improvements by reducing approximately 21% of impinging velocity near to the aortic wall, and more than 58% reduction on total force generated as compared to standard cannula.
  12. Abbas SS, Nasif MS, Al-Waked R, Meor Said MA
    Artif Organs, 2020 Feb;44(2):E20-E39.
    PMID: 31378963 DOI: 10.1111/aor.13536
    Platelet activation induced by shear stresses and non-physiological flow field generated by bileaflet mechanical heart valves (BMHVs) leads to thromboembolism, which can cause fatal consequences. One of the causes of platelet activation could be intermittent regurgitation, which arises due to asynchronous movement and rebound of BMHV leaflets during the valve closing phase. In this numerical study, the effect of intermittent regurgitation on the platelet activation potential of BMHVs was quantified by modeling a BMHV in the straight and anatomic aorta at implantation tilt angles 0°, 5°, 10°, and 20°. A fully implicit Arbitrary Lagrangian-Eulerian-based Fluid-Structure Interaction formulation was adopted with blood modeled as a multiphase, non-Newtonian fluid. Results showed that the intermittent regurgitation and consequently the platelet activation level increases with the increasing implantation tilt of BMHV. For the straight aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 20° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 8.5°, 3°, and 0°, respectively. For the anatomic aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 24° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 14°, 10°, and 7°, respectively. For all the implantation orientations of BMHVs, intermittent regurgitation and platelet activation were always higher in the anatomic aorta than in the straight aorta. The study concludes that the pivot axis of BMHV must be implanted parallel to the aortic root's curvature to minimize intermittent regurgitation and platelet activation.
  13. Alkhatib SE, Tarlochan F, Mehboob H, Singh R, Kadirgama K, Harun WSBW
    Artif Organs, 2019 Jul;43(7):E152-E164.
    PMID: 30805945 DOI: 10.1111/aor.13444
    The mismatch between stiffness of the femoral dense stem and host bone causes complications to patients, such as aseptic loosening and bone resorption. Three-dimensional finite-element models of homogeneous porous (HGP) and functionally graded porous (FGP) stems incorporating body-centered cubic (BCC) structures are proposed in this article as an alternative to the dense stems. The relationship between the porosity and strut thickness of the BCC structure was developed to construct the finite-element models. Three levels of porosities (20%, 50%, and 80%) were modeled in HGP and FGP stems. The porosity of the stems was decreased distally according to the sigmoid function (n = 0.1, n = 1 and n = 10) with 3 grading exponents. The results showed that FGP stems transferred 120%-170% higher stresses to the femur (Gruen zone 7) as compared to the solid stem. Conversely, the stresses in HGP and FGP stems were 12%-34% lower than the dense stem. The highest micromotions (105-147 µm) were observed for stems of 80% overall porosity, and the lowest (42-46 µm) was for stems of 20% overall porosity. Finally, FGP stems with a grading exponent of n = 10 resulted in an 11%-28% reduction in micromotions.
  14. Zaman SU, Saif-Ur-Rehman, Zaman MKU, Rafiq S, Arshad A, Khurram MS, et al.
    Artif Organs, 2021 Nov;45(11):1377-1390.
    PMID: 34152645 DOI: 10.1111/aor.14020
    In the current study, a phase inversion scheme was employed to fabricate hydroxyapatite (HA)/polysulfone (PSF)-based asymmetric membranes using a film applicator with water as a solvent and nonsolvent exchanging medium. Fourier Transform Infrared (FTIR) and X-ray diffraction (XRD) spectroscopic studies were conducted to confirm the bonding chemistry and purity of filler. The inherent thick nature of PSF generated sponge-like shape while the instantaneous demixing process produced finger-like pore networks in HA/PSF-based asymmetric membranes as exhibited by scanning electron microscope (SEM) micrographs. The FTIR spectra confirmed noncovalent weak attractions toward the polymer surface. The leaching ratio was evaluated to observe the dispersion behavior of HA filler in membrane composition. Hydrophilicity, pore profile, pure water permeation (PWP) flux, and molecular weight cutoff (MWCO) values of all formulated membranes were also calculated. Antifouling results revealed that HA modified PSF membranes exhibited 43% less adhesion of bovine serum albumin (BSA) together with >86% recovery of flux. Membrane composition showed 74% total resistance, out of which 60% was reversible resistance. Biocompatibility evaluation revealed that the modified membranes exhibited prothrombin time (PT), and thrombin time (TT) comparable with typical blood plasma, whereas proliferation of living cells over membrane surface proved its nontoxic behavior toward biomedical application. The urea and creatinine showed effective adsorption aptitude toward HA loaded PSF membranes.
  15. Anita Lett J, Sagadevan S, Léonard E, Fatimah I, Motalib Hossain MA, Mohammad F, et al.
    Artif Organs, 2021 Dec;45(12):1501-1512.
    PMID: 34309044 DOI: 10.1111/aor.14045
    The primary role of bone tissue engineering is to reconcile the damaged bones and facilitate the speedy recovery of the injured bones. However, some of the investigated metallic implants suffer from stress-shielding, palpability, biocompatibility, etc. Consequently, the biodegradable scaffolds fabricated from polymers have gathered much attention from researchers and thus helped the tissue engineering sector by providing many alternative materials whose functionality is similar to that of natural bones. Herein, we present the fabrication and testing of a novel composite, magnesium (Mg)-doped hydroxyapatite (HAp) glazed onto polylactic acid (PLA) scaffolds where polyvinyl alcohol (PVA) used as a binder. For the composite formation, Creality Ender-3 pro High Precision 3D Printer with Shape tool 3D Technology on an FSD machine operated by Catia design software was employed. The composite has been characterized for the crystallinity (XRD), surface functionality (FTIR), morphology (FESEM), biocompatibility (hemolytic and protein absorption), and mechanical properties (stress-strain and maximum compressive strength). The powder XRD analysis confirmed the semicrystalline nature and intact structure of HAp even after doping with Mg, while FTIR studies for the successful formation of Mg-HAp/PVA@PLA composite. The FESEM provided analysis indicated for the 3D porous architecture and well-defined morphology to efficiently transport the nutrients, and the biocompatibility studies are supporting that the composite for blood compatible with the surface being suitable enough for the protein absorption. Finally, the composite's antibacterial activity (against Staphylococcus aureus and Escherichia coli) and the test of mechanical properties supported for the enhanced inhibition of active growth of microorganisms and maximum compressive strength, respectively. Based on the research outcomes of biocompatibility, antibacterial activity, and mechanical resistance, the fabricated Mg-HAp/PVA@PLA composite suits well as a promising biomaterial platform for orthopedic applications by functioning towards the open reduction internal fixation of bone fractures and internal repairs.
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