Past and future of blood damage modelling in a view of translational research

2018 ◽  
Vol 42 (3) ◽  
pp. 125-132 ◽  
Author(s):  
Leonid Goubergrits ◽  
Ulrich Kertzscher ◽  
Michael Lommel
Keyword(s):  
Residence Time ◽  
High Velocity ◽  
Heart Valves ◽  
Pressure Fluctuations ◽  
Artificial Organs ◽  
Blood Damage ◽  
Damage Models ◽  
Heart Assist Devices

Anatomic pathologies such as stenosed or regurgitating heart valves and artificial organs such as heart assist devices or heart valve prostheses are associated with non-physiological flow. This regime is associated with regions of spatially high-velocity gradients, high-velocity and/or pressure fluctuations as well as neighbouring regions with stagnant flow associated with high residence time. These hemodynamic conditions cause destruction and/or activation of blood components and their accumulation in regions with high residence time. The development of next-generation artificial organs, which allow long-term patient care by reducing adverse events and improve quality of life, requires the development of blood damage models serving as a cost function for device optimization. We summarized the studies underlining the key findings with subsequent elaboration of the requirements for blood damage models as well as a decision tree based on the classification of existing blood damage models. The four major classes are Lagrangian or Eulerian approaches with stress- or strain-based blood damage. Key challenges were identified and future steps towards the translation of blood damage models into the device development pipeline were formulated. The integration of blood damage caused by turbulence into models as well as in vitro and in vivo validation of models remain the major challenges for future developments. Both require the development of novel experimental setups to provide reliable and well-documented experimental data.

The Influence of Open Leaflet Geometry on the Haemodynamic Flow Characteristics of Polyurethane Trileaflet Artificial Heart Valves

1996 ◽  
Vol 210 (4) ◽  
pp. 273-287 ◽  
Author(s):  
J Corden ◽  
T David ◽  
J Fisher
Keyword(s):  
Axial Velocity ◽  
Heart Valves ◽  
Flow Characteristics ◽  
Manufacturing Method ◽  
Blood Damage ◽  
Flow Recirculation ◽  
Maximum Value ◽  
Artificial Heart Valves

In vitro velocity data were obtained downstream of two versions of the Leeds polyurethane trileaflet heart valve in a simulated pulsatile flow regime using laser Doppler velocimetry. The main difference between the two valves studied was the manufacturing method used to create the valves. The film-fabricated valve was constructed from solvent-cast sheets of polyurethane, thermally formed into the correct leaflet geometry. The dip-cast valve used a stainless steel mould which was dipped into a polyurethane solution to produce the valve leaflets. Significant differences were visible between the fully open leaflet shape of each valve. The distribution of mean axial velocity and Reynolds normal stress (RNS) was shown to be dependent on the shape of the fully open valve orifice. For the film-fabricated valves, flow recirculation and high values of RNS were present downstream of the frame posts. The maximum value of RNS obtained downstream of the film-fabricated valve at peak systole was 147 N/m2. Results for the dip-cast valve showed a more uniform distribution of mean axial velocity and RNS resulting from the more circular central orifice produced by the dip-cast leaflets. The maximum value of RNS obtained downstream of the dip-cast valve at peak systole was 109 N/m2. These results demonstrate the effect of the open valve geometry on the flow characteristics downstream of trileaflet valves and that minor changes to the open leaflet geometry can significantly affect the flow characteristics and the possibility of flow-related blood damage occurring in vivo.

scholarly journals Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

2011 ◽  
Vol 61 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Komuravelly Someshwar ◽  
Kalyani Chithaluru ◽  
Tadikonda Ramarao ◽  
K. Kumar
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Release Kinetics ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Floating Tablets ◽  
Gastric Residence Time

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

Calcification Modelling in Artificial Heart Valves

1992 ◽  
Vol 15 (5) ◽  
pp. 284-288 ◽  
Author(s):  
A.C. Fisher ◽  
G.M. Bernacca ◽  
T.G. Mackay ◽  
W.R. Dimitri ◽  
R. Wilkinson ◽  
...  
Keyword(s):  
Artificial Heart ◽  
Heart Valves ◽  
Test Protocol ◽  
Tissue Sections ◽  
Artificial Heart Valves ◽  
In Vivo Tests ◽  
Tissue Contents ◽  
Histological Staining

This study has examined a range of methods of studying the calcification process in bovine pericardial and polyurethane biomaterials. The calcification methods include static and dynamic, in vitro and in vivo tests. The analytical methods include measurement of depletion rates of calcium and phosphate from in vitro calcifying solutions, analysis of tissue contents of calcium, histological staining of tissue sections for calcium, X-ray elemental analysis, by scanning electron microscopy, of calcium and phosphorus distributions over valve leaflets calcified in vitro under dynamic conditions. Bovine pericardium, in all test settings, calcified to a much greater degree than polyurethane biomaterials. Polyurethane extracts calcified to a greater degree than bulk polyurethanes. The test protocol used allows progress through increasily demanding calcification tests, with the possibility of eliminating unsuitable materials with tests of limited complexity and expense.

Organic Polymer Biocompatibility and Toxicology

1972 ◽  
Vol 18 (9) ◽  
pp. 869-894 ◽  
Author(s):  
Fritz Bischoff
Keyword(s):  
Food Packaging ◽  
Heart Valves ◽  
Chemical Carcinogenesis ◽  
Artificial Organs ◽  
Organic Polymer ◽  
Degradation Reactions ◽  
Contraceptive Devices ◽  
Heart Assist Devices ◽  
Liquid Silicone ◽  
Artificial Kidneys

Abstract Adverse effects of organic polymers used for plasma extenders, tissue adhesives, bone cements, contraceptive devices, prostheses, artificial organs, food packaging, cooking, and laboratory ware are appraised. Parenteral polymer disintegration involves hydrolytic, redox, and degradation reactions. Accumulative toxicity of plasticizers, antioxidants, and monomers liberated from plastic containers warrants investigation. Main problems with heart-assist devices are clotting and blood destruction; with plasma extenders, thesaurismotic reactions; with acrylic bone glues, transitory hypotension; with artificial kidneys, loss of metabolic essentials; with silicone heart valves, uptake of lipids; with silicone chin implants, bone resorption; and with liquid silicone mammary amplification, lumpy breasts and mastitis. A polymer fume fever is linked with pyrolysis of polytetrafluoroethylene. Human solid-state carcinogenesis constitutes a calculated risk with polymer implants. In rodents, all solid polymers tested produced cancer; chemical carcinogenesis was induced by a polyvinyl chloride copolymer, vinyl chloride, polycaprolactam, liquid silicone, and some brands of polytetrafluoroethylene.

scholarly journals In Silico Performance of a Recellularized Tissue-Engineered Transcatheter Aortic Valve

2019 ◽  
Vol 141 (6) ◽  
Author(s):  
Christopher Noble ◽  
Joshua Choe ◽  
Susheil Uthamaraj ◽  
Milton Deherrera ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Mechanical Behavior ◽  
Heart Valves ◽  
Mechanical Response ◽  
Mechanical Performance ◽  
Fe Analysis ◽  
Model Parameters ◽  
Biaxial Testing ◽  
Principal Stresses

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissue-engineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.

scholarly journals HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study

2019 ◽  
Vol 17 (3) ◽  
pp. 228080001986707 ◽  
Author(s):  
Cristian Guarise ◽  
Carlo Barbera ◽  
Mauro Pavan ◽  
Susi Panfilo ◽  
Riccardo Beninatto ◽  
...  
Keyword(s):  
Residence Time ◽  
Rabbit Model ◽  
Diglycidyl Ether ◽  
In Vitro Cytotoxicity ◽  
Dermal Filler ◽  
Dermal Fillers ◽  
Process Comparison ◽  
Hygroscopic Properties

The success of hyaluronic acid (HA)-based dermal fillers, with more than 2 million minimally invasive procedures conducted in 2016 in the US alone, is due to their hygroscopic properties of biocompatibility and reversibility. The type and density of HA cross-linkage, as well as the manufacturing technology, may influence not only the in vivo persistence but also the safety profile of dermal fillers. 1,4-Butanediol diglycidyl ether (BDDE) is the cross-linker used in most market-leading HA fillers; 1,4-butanediol di-(propan-2,3-diolyl) ether (BDPE) is the major impurity obtained from the HA–BDDE cross-linking (HBC) process. In this work, a new process to obtain high purity HBC fillers was developed. A new HPLC-MS method was validated for the quantification of BDPE content in HBC dermal fillers. In vitro cytotoxicity of BDPE was evaluated in fibroblasts (IC50 = 0.48 mg/mL). The viscoelasticity was monitored during the shelf-life of the HBC-10% hydrogel and was correlated with in vitro hyaluronidase resistance and in vivo residence time in a rabbit model. This analysis showed that elasticity is the best parameter to predict the in vivo residence time. Finally, a series of parameters were investigated in certain marketed dermal fillers and were compared with the results of the HBC-10% hydrogel.

In Vitro Thrombogenicity Testing of Artificial Organs

1998 ◽  
Vol 21 (9) ◽  
pp. 548-552 ◽  
Author(s):  
R. Paul ◽  
O. Marseille ◽  
E. Hintze ◽  
L. Huber ◽  
H. Schima ◽  
...  
Keyword(s):  
Heart Valves ◽  
Early Stage ◽  
Thrombus Formation ◽  
Testing Procedure ◽  
Artificial Organs ◽  
Coagulation System ◽  
In Vitro Testing ◽  
Animal Testing ◽  
Thrombogenic Potential

Thromboembolic complications remain as one of the main problems for blood contacting artificial organs such as heart valves, bloodpumps and others. In vitro evaluation of thrombogenesis in prototypes has not previously been part of the standard evaluation of these devices. In comparison to hemolysis testing, evaluation of the thrombogenic potential is more difficult to perform because of the complexity of the blood coagulation system. We present an in vitro testing procedure that allows the accelerated examination of the thrombogenic potential of different types of blood pumps. Additionally, first results are presented that indicate the reliability of the accelerated clotting test for mechanical heart valves. Results for the centrifugal pump BioMedicus and two microaxial pumps have shown typical thrombus formation at locations such as bearings. The results indicate that the accelerated clotting test is an excellent addition to the much more expensive animal testing of artificial organs or assist devices. In vitro testing permits studies of thrombus formation to be performed at an early stage and at low costs and also facilitates a more precise investigation of device areas known to be potential hot spots for thrombus formation.

Simulation of the Role of Oscillatory Shear Stress on Mesenchymal Stem Cell Proliferation and Extracellular Matrix Production in Engineered Heart Valve Tissue Formation

2013 ◽  
Author(s):  
João S. Soares ◽  
Trung B. Le ◽  
Fotis Sotiropoulos ◽  
Michael S. Sacks
Keyword(s):  
Extracellular Matrix ◽  
Heart Valves ◽  
Structural Evolution ◽  
Biodegradable Scaffolds ◽  
Cell Sources ◽  
Hemodynamic Performance ◽  
Tissue Engineered Heart Valves ◽  
Oscillatory Shear Stress

Living tissue engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. TEHV have been constructed by seeding vascular-derived autologous cells onto biodegradable scaffolds and exhibited enhanced extracellular matrix (ECM) development when cultured under pulsatile flow conditions in-vitro [2]. After functioning successfully for up to 8 months in the pulmonary circulation of growing lambs, TEHV underwent extensive in vivo remodeling and structural evolution and have demonstrated the feasibility of engineering living heart valves in vitro [3]. The employment of novel cell sources, which are clinically obtainable in principle such as bone marrow-derived mesenchymal stem cells (MSCs), is key to achieve viable clinical application [4].

A New Method for Evaluation of Cavitation Near Mechanical Heart Valves

2003 ◽  
Vol 125 (5) ◽  
pp. 663-670 ◽  
Author(s):  
Peter Johansen ◽  
Keefe B. Manning ◽  
John M. Tarbell ◽  
Arnold A. Fontaine ◽  
Steven Deutsch ◽  
...  
Keyword(s):  
High Frequency ◽  
Heart Valves ◽  
A Priori ◽  
Pressure Fluctuations ◽  
Mechanical Heart Valves ◽  
New Method ◽  
Pass Filter ◽  
Bandwidth Limitation ◽  
High Pass

Evaluation of cavitation in vivo is often based on recordings of high-pass filtered random high-frequency pressure fluctuations. We hypothesized that cavitation signal components are more appropriately assessed by a new method for extraction of random signal components of the pressure signals. We investigated three different valve types and found a high correlation between the two methods r2:0.8806−0.9887. The new method showed that the cavitation signal could be extracted without a priori knowledge needed for setting the high-pass filter cut off frequency, nor did it introduce bandwidth limitation of the cavitation signal.

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