Biofunctionalization of surfaces to minimize undesirable effects in cardiovascular assistance devices

BACKGROUND: The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. METHODS: Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3µm as (TSA) and (4) Textured with 2.4µm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. RESULTS: After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

Biofunctionalization of surfaces to minimize undesirable effects in cardiovascular assistance devices.

BACKGROUND: The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. METHODS: Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3µm as (TSA) and (4) Textured with 2.4µm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. RESULTS: After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

Bioabsorbable Polymeric Stent for the Treatment of Coarctation of the Aorta (CoA) in Children: A Methodology to Evaluate the Design and Mechanical Properties of PLA Polymer.

This study presents a methodology that combines experimental tests and the finite element method, which is able to analyse the influence of the geometry on the mechanical behaviour of stents made of bioabsorbable polymer PLA (PolyLactic Acid) during their expansion in the treatment of coarctation of the aorta (CoA). Tensile tests with standardized specimen samples were conducted to determine the properties of a 3D-printed PLA. A finite element model of a new stent prototype was generated from CAD files. A rigid cylinder simulating the expansion balloon was also created to simulate the stent opening performance. A tensile test with 3D-printed customized stent specimens was performed to validate the FE stent model. Stent performance was evaluated in terms of elastic return, recoil, and stress levels. The 3D-printed PLA presented an elastic modulus of 1.5 GPa and a yield strength of 30.6 MPa, lower than non-3D-printed PLA. It can also be inferred that crimping had little effect on stent circular recoil performance, as the difference between the two scenarios was on average 1.81%. For an expansion of diameters ranging from 12 mm to 15 mm, as the maximum opening diameter increases, the recoil levels decrease, ranging from 10 to 16.75% within the reported range. These results point out the importance of testing the 3D-printed PLA under the conditions of using it to access its material properties; the results also indicate that the crimping process could be disregarded in simulations to obtain fast results with lower computational cost and that new proposed stent geometry made of PLA might be suitable for use in CoA treatments-the approach that has not been applied before. The next steps will be to simulate the opening of an aorta vessel using this geometry.

Computational fluid dynamics improvements and in vitro tests of a proposed transventricular axial blood pump

Heart failure is a chronic disease that affects thousands of people around the world, being characterized by the inability of one's heart to adequately pump their blood according to their body's needs. Its treatment may be performed through heart transplant. However, ventricular assist devices (VADs) can be used as a way to assist the patient while they wait for a transplant or as destination therapy, with them being responsible for the patients increase in the life expectancy. These devices are pumps that help supply the adequate cardiac output to the body. But the procedures used to implant this kind of device, the size and geometry of the pump are vital for the surgery success and assurance safety patient recuperation. Because of that many important researches center try to find pump geometry that comply these characteristics and comply human blood physiology. Then the reduction in size of these systems, which increases their reliability, biocompatibility and robustness, is essential to the complete implantation of the VADs, which is the main focus of the current state of art.

Bioabsorbable polymeric Stent for the treatment of Coarctation of the Aorta (CoA) in children: A methodology to evaluate the design and mechanical properties of PLA polymer

This study presents a methodology that combines experimental tests and the finite element method, which is able to analyse the influence of the geometry on the mechanical behaviour of stents made of bioabsorbable polymer PLA (PolyLactic Acid) during their expansion in the treatment of coarctation of the aorta (CoA). Tensile tests with standardized specimen samples were conducted to determine the properties of a 3D-printed PLA. A finite element model of a new stent prototype was generated from CAD files. A rigid cylinder simulating the expansion balloon was also created to simulate the stent opening performance. A tensile test with 3D-printed customized stent specimens was performed to validate the FE stent model. Stent performance was evaluated in terms of elastic return, recoil, and stress levels. The 3D-printed PLA presented an elastic modulus of 1.5 GPa and a yield strength of 30.6 MPa, lower than non-3D-printed PLA. It can also be inferred that crimping had little effect on stent circular recoil performance, as the difference between the two scenarios was on average 1.81%. For an expansion of diameters ranging from 12 mm to 15 mm, as the maximum opening diameter increases, the recoil levels decrease, ranging from 10 to 16.75% within the reported range. These results point out the importance of testing the 3D-printed PLA under the conditions of using it to access its material properties; the results also indicate that the crimping process could be disregarded in simulations to obtain fast results with lower computational cost and that new proposed stent geometry made of PLA might be suitable for use in CoA treatments-the approach that has not been applied before. The next steps will be to simulate the opening of an aorta vessel using this geometry.

Research and development of ventricular assist devices from a single center in Latin America

OBJECTIVES: Ventricular assist devices have been widely accepted as an alternative treatment for advanced heart failure, while heart transplantation is a limited procedure because of the shortage of donors. In face of a scarce availability of these devices, many centers around the world have developed their own technologies. The Institute Dante Pazzanese of Cardiology holds a dedicated engineering center for mechanical circulatory support, being responsible for creating several prototypes and notable devices, like the first Brazilian artificial heart. The objectives of this study were to provide both a historical overview and a detailed characterization of each original device developed by the center. METHODS: We describe historical and technical features of the main ventricular assist devices developed at the Institute Dante Pazzanese of Cardiology through a focused review on the institute's scientific and technical production on ventricular assist devices or blood pumps, from 1990 to 2022, indexed in the electronic databases Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, and the Scientific Electronic Library Online (SciELO). RESULTS: The following devices were selected from the review: (1) The Spiral Pump is a disposable centrifugal pump with an internal conically shaped rotor, a spiral impeller, which carries threads on its surface. The device was designed for cardiopulmonary bypass in 1992, passed through consecutive design modifications and preclinical tests until approval for clinical application in 2007. (2) The Auxiliary Total Artificial Heart is an electromechanical pulsatile blood pump with left and right chambers, originally designed in 1995 to work as a heterotopic artificial heart. Preclinical studies evaluated hydrodynamic performance in mock circulatory loops and in vivo implants were performed in calves from 1999 to 2009. In 2012, it became the first nationally conceived artificial heart approved for clinical trials in Brazil. (3) The Implantable Centrifugal Blood Pump was conceived in 2006 for long-term circulatory assistance with a unique impeller design concept producing a mixed flow. Preclinical studies included hydrodynamic and hemolysis tests, analysis in a hybrid cardiovascular simulator and anatomical positioning in calves. (4) The Apico-Aortic Blood Pump consists of a miniaturized centrifugal pump originally conceived in 2012 for bridge to transplantation strategy. Preclinical studies included hydrodynamic and hemolysis tests, analysis in a hybrid cardiovascular simulator and anatomical positioning in pigs. (5) The Temporary Circulatory Support Device is a new centrifugal blood pump for temporary ventricular assistance developed with the purpose of bridge to decision or bridge to recovery strategies. Originally conceived in 2013, preclinical studies on the device consisted only of hydrodynamic and hemolysis tests. CONCLUSION: From the academic point of view, Brazil count on a few groups with a considerable output in ventricular assist device research and development. Notable devices produced at Institute Dante Pazzanese of Cardiology, from a total artificial heart to varied and innovative centrifugal pumps, have demonstrated excellent results for future clinical applications. More financial and institutional support are needed for the continuation of these promising research projects.

Laser-Treated Surfaces for VADs: From Inert Titanium to Potential Biofunctional Materials.

Objective. Laser-treated surfaces for ventricular assist devices. Impact Statement. This work has scientific impact since it proposes a biofunctional surface created with laser processing in bioinert titanium. Introduction. Cardiovascular diseases are the world's leading cause of death. An especially debilitating heart disease is congestive heart failure. Among the possible therapies, heart transplantation and mechanical circulatory assistance are the main treatments for its severe form at a more advanced stage. The development of biomaterials for ventricular assist devices is still being carried out. Although polished titanium is currently employed in several devices, its performance could be improved by enhancing the bioactivity of its surface. Methods. Aiming to improve the titanium without using coatings that can be detached, this work presents the formation of laser-induced periodic surface structures with a topology suitable for cell adhesion and neointimal tissue formation. The surface was modified by femtosecond laser ablation and cell adhesion was evaluated in vitro by using fibroblast cells. Results. The results indicate the formation of the desired topology, since the cells showed the appropriate adhesion compared to the control group. Scanning electron microscopy showed several positive characteristics in the cells shape and their surface distribution. The in vitro results obtained with different topologies point that the proposed LIPSS would provide enhanced cell adhesion and proliferation. Conclusion. The laser processes studied can create new interactions in biomaterials already known and improve the performance of biomaterials for use in ventricular assist devices.

Safety control architecture for ventricular assist devices

ABSTRACT: In patients with severe heart disease, the implantation of a ventricular assist device (VAD) may be necessary, especially in patients with an indication for heart transplantation. For this, the Institute Dante Pazzanese of Cardiology (IDPC) has developed an implantable centrifugal blood pump that will be able to help a diseased human heart to maintain physiological blood flow and pressure. This device will be used as a totally or partially implantable VAD. Therefore, performance assurance and correct specification of the VAD are important factors in achieving a safe interaction between the device and the patient's behavior or condition. Even with reliable devices, some failures may occur if the pumping control does not keep up with changes in the patient's behavior or condition. If the VAD control system has no fault tolerance and no system dynamic adaptation that occurs according to changes in the patient's cardiovascular system, a number of limitations can be observed in the results and effectiveness of these devices, especially in patients with acute comorbidities. This work proposes the application of a mechatronic approach to this class of devices based on advanced control, instrumentation, and automation techniques to define a method to develop a hierarchical supervisory control system capable of dynamically, automatically, and safely VAD control. For this methodology, concepts based on Bayesian networks (BN) were used to diagnose the patient's cardiovascular system conditions, Petri nets (PN) to generate the VAD control algorithm, and safety instrumented systems to ensure the safety of the VAD system.

In vitro evaluation of multi­objective physiological control of the centrifugal blood pump

Left ventricular assist devices (LVADs) have been used as a bridge to transplantation or as destination therapy to treat patients with heart failure (HF). The inability of control strategy to respond automatically to changes in hemodynamic conditions can impact the patients' quality of life. The developed control system/algorithm consists of a control system that harmoniously adjusts pump speed without additional sensors, considering the patient's clinical condition and his physical activity. The control system consists of three layers: (a) Actuator speed control; (b) LVAD flow control (FwC); and (c) Fuzzy control system (FzC), with the input variables: heart rate (HR), mean arterial pressure (MAP), minimum pump flow, level of physical activity (data from patient), and clinical condition (data from physician, INTERMACS profile). FzC output is the set point for the second LVAD control schemer (FwC) which in turn adjusts the speed. Pump flow, MAP, and HR are estimated from actuator drive parameters (speed and power). Evaluation of control was performed using a centrifugal blood pump in a hybrid cardiovascular simulator, where the left heart function is the mechanical model and right heart function is the computational model. The control system was able to maintain MAP and cardiac output in the physiological level, even under variation of EF. Apart from this, also the rotational pump speed is adjusted following the simulated clinical condition. No backflow from the aorta in the ventricle occurred through LVAD during tests. The control algorithm results were considered satisfactory for simulations, but it still should be confirmed during in vivo tests.

Apical aortic blood pump preclinical assessment for long­term use: durability test and stator topology to reduce wear in the bearing system

This study presents an assessment for long­term use of the apical aortic blood pump (AABP), focusing on wear reduction in the bearing system. AABP is a centrifugal left ventricle assist device initially developed for bridge to transplant application. To analyze AABP performance in long­term applications, a durability test was performed. This test indicated that wear in the lower bearing pivot causes device failure in long­term. A wear test in the bearing system was conducted to demonstrate the correlation of the load in the bearing system with wear. Results from the wear test showed a direct correlation between load and wear at the lower bearing pivot. In order to reduce load, thus reducing wear, a new stator topology has been proposed. In this topology, a radial stator would replace the axial stator previously used. Another durability test with the new stator has accounted twice the time without failure when compared with the original model.

A strategy for designing of customized electromechanical actuators of blood pumps

Congestive heart failure is a pathology of global incidence that affects millions of people worldwide. When the heart weakens and fails to pump blood at physiological rates commensurate with the requirements of tissues, two main alternatives are cardiac transplant and ventricular assist devices (VADs). This article presents the design strategy for development of a customized VAD electromagnetic actuator. Electromagnetic actuator is a brushless direct current motor customized to drive the pump impeller by permanent magnets located in rotor­stator coupling. In this case, ceramic pivot bearings support the VAD impeller. Electronic circuitry controls rotation switching current in stator coils. The proposed methodology consisted of analytical numerical design, tridimensional computational modeling, numerical simulations using Maxwell software, actuator prototyping, and validation in the dynamometer. The axial flow actuator was chosen by its size and high power density compared to the radial flow type. First step consisted of estimating the required torque to drive the pump. Torque was estimated at 2100 rpm and mean current of 0.5 A. Numerical analysis using finite element method mapped vectors and fields to build stator coils and actuator assemblage. After tests in the dynamometer, experimental results were compared with numerical simulation and validated the proposed model. In conclusion, the proposed methodology for designing of VAD electromechanical actuator was considered satisfactory in terms of data consistency, feasibility, and reliability.

Impeller geometry definition of the transventricular assist device

ABSTRACT: According to the World Health Organization, cardiovascular disease is the number one cause of death worldwide, except Africa, where Acquired Immune Deficiency Syndrome is the leading cause of death. In this scenario, the ventricular assist device (VAD) remains the unique alternative to extend patient life until heart transplantation. At Dante Pazzanese Institute of Cardiology, the research and development of an axial flow VAD to be fully implantable within the heart was started. This pump, denominated Transventricular Assist Device (TVAD), can be surgically implanted through a small left intercostal incision in a minimally invasive manner. The goal of this work is to analyze the impeller geometries of the TVAD, to avoid high shear stresses in the fluid and aim for the best conditions to support the circulatory system using computational fluid dynamics and in vitro tests. Different rotor geometries were selected according to the literature; based on the results, the best rotor was elected. This rotor contains a pair of spiral blades of constant and relatively high pitch, which pumps liquid at a flow rate of 3 L/min at 73 mm Hg. It is also expected that this rotor presents a moderate hemolysis since the shear rate is acceptable.

Development of a prototype anti-pollution filter for volatile anesthetics

Introduction: The use of volatile agents during cardiopulmonary bypass allows a "single drug anesthesia" and is associated with reduced peak postoperative troponin levels. Connecting the exhaust systems to the oxygenator's gas outlet port is mandatory and allows to prevent operating room (but not atmospheric) pollution by volatile agents. The aim of this study was to create a prototype filter for volatile agents and to test its adsorption efficacy during an ex-vivo simulated conventional cardiopulmonary bypass test. Methods: We carried out bench tests to conceive a prototype filter that could prevent room and environment pollution without damaging membrane oxygenators. We performed the tests at the Engineering Center for Circulatory Assistance Laboratory, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. Bench tests included simulation of integral adsorption tests, filter dimensions and design, flow versus pressure curve, sizing, and tightness. Results: Calgon AT 410 was the best kind of activated charcoal granules for adsorption of sevoflurane, isoflurane, and desflurane. Filter dimension tests showed that a chamber of 30-cm width over 10-cm diameter filled with 200g of the Calgon AT410 granules was the minimum required to fully adsorb sevoflurane for 90min. Adsorption tests showed that the prototype filter fully adsorbed isoflurane in 100±2.3min, sevoflurane in 95±3.4min, and desflurane in 95±4.3min. Conclusion: The new version of our prototype filter adsorbed most of the volatile anesthetics agents during an ex-vivo simulated conventional cardiopulmonary bypass test.

Impeller geometry definition of the transventricular assist device.

According to the World Health Organization, cardiovascular disease is the number one cause of death worldwide, except Africa, where Acquired Immune Deficiency Syndrome is the leading cause of death. In this scenario, the ventricular assist device (VAD) remains the unique alternative to extend patient life until heart transplantation. At Dante Pazzanese Institute of Cardiology, the research and development of an axial flow VAD to be fully implantable within the heart was started. This pump, denominated Transventricular Assist Device (TVAD), can be surgically implanted through a small left intercostal incision in a minimally invasive manner. The goal of this work is to analyze the impeller geometries of the TVAD, to avoid high shear stresses in the fluid and aim for the best conditions to support the circulatory system using computational fluid dynamics and in vitro tests. Different rotor geometries were selected according to the literature; based on the results, the best rotor was elected. This rotor contains a pair of spiral blades of constant and relatively high pitch, which pumps liquid at a flow rate of 3 L/min at 73 mm Hg. It is also expected that this rotor presents a moderate hemolysis since the shear rate is acceptable.

In vitro evaluation of multi-objective physiological control of the centrifugal blood pump.

Left ventricular assist devices (LVADs) have been used as a bridge to transplantation or as destination therapy to treat patients with heart failure (HF). The inability of control strategy to respond automatically to changes in hemodynamic conditions can impact the patients' quality of life. The developed control system/algorithm consists of a control system that harmoniously adjusts pump speed without additional sensors, considering the patient's clinical condition and his physical activity. The control system consists of three layers: (a) Actuator speed control; (b) LVAD flow control (FwC); and (c) Fuzzy control system (FzC), with the input variables: heart rate (HR), mean arterial pressure (MAP), minimum pump flow, level of physical activity (data from patient), and clinical condition (data from physician, INTERMACS profile). FzC output is the set point for the second LVAD control schemer (FwC) which in turn adjusts the speed. Pump flow, MAP, and HR are estimated from actuator drive parameters (speed and power). Evaluation of control was performed using a centrifugal blood pump in a hybrid cardiovascular simulator, where the left heart function is the mechanical model and right heart function is the computational model. The control system was able to maintain MAP and cardiac output in the physiological level, even under variation of EF. Apart from this, also the rotational pump speed is adjusted following the simulated clinical condition. No backflow from the aorta in the ventricle occurred through LVAD during tests. The control algorithm results were considered satisfactory for simulations, but it still should be confirmed during in vivo tests.