Effect of bioprosthetic leaflet anisotropy on stent dynamics of Transcatheter Aortic Valve Replacement devices.

The assessment of stent fatigue in Transcatheter Aortic Valve Replacement (TAVR) systems is critical for the design of next-generation devices, both in vitro and in vivo. The mechanical properties of the bioprosthetic heart valves (BHVs) have a significant impact on the fatigue life of the metallic stent and thus must be taken into consideration when evaluating new TAVR device designs. This study aims to investigate the relationship between BHV anisotropic behaviour and the asymmetric deflections of the stent frame observed during in vitro testing. An explicit dynamics finite element model of the nitinol stent with attached bioprosthetic valve leaflets was developed to evaluate the deflections of the TAVR device under haemodynamic loading. Our results demonstrate that pericardium behaviour plays a dominant role in determining stent frame deflection. The anisotropic behaviour of the leaflets, resulting from collagen fibre orientation, affects the extent of deflection encountered by each commissure of the frame. This leads to asymmetric variation in frame deflection that can influence the overall fatigue life of the nitinol stent. This study highlights the importance of considering both the flexible nature of the metallic stent as well as the leaflet anisotropic behaviour in the design and fatigue assessment of TAVR systems.

Investigation of anti-adhesion ability of 8-arm PEGNHS-modified porcine pericardium.

In post-adhesion surgery, there is a clinical need for anti-adhesion membranes specifically designed for the liver, given the limited efficacy of current commercial products. To address this demand, we present a membrane suitable for liver surgery applications, fabricated through the modification of decellularized porcine pericardium with 20 KDa hexaglycerol octa (succinimidyloxyglutaryl) polyoxyethylene (8-arm PEGNHS). We also developed an optimized modification procedure to produce a high-performance anti-adhesion barrier. The modified membrane significantly inhibited fibroblast cell adherence while maintaining minimal levels of inflammation. By optimizing the modification ratio, we successfully controlled post-adhesion formation. Notably, the 8-arm PEG-modified pericardium with a molar ratio of 5 exhibited the ability to effectively prevent post-adhesion formation on the liver compared to both the control and Seprafilm®, with a low adhesion score of 0.5 out of 3.0. Histological analysis further confirmed its potential for easy separation. Furthermore, the membrane demonstrated regenerative capabilities, as evidenced by the proliferation of mesothelial cells on its surface, endowing anti-adhesion properties between the abdominal wall and liver. These findings highlight the membrane's potential as a reliable barrier for repeated liver resection procedures that require the removal of the membrane multiple times.

Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction.

Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.

Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications.

Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly (p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized tissues were biocompatible with persistent growth of the adipose stem cells over 30 days. The staining confirmed cell adherence either to the peripheries of the materials or within their matrices. Moreover, the in vivo investigation confirmed the biocompatibility and degradability of the decellularized scaffolds. Conclusively, Trypsin + TX + SDS is a successful new protocol for tissue decellularization. Moreover, decellularized pericardia and tunica vaginalis are promising scaffolds for the engineering of different tissues with higher potential for the use of DPP in cardiovascular applications and DBP and DPTV in the reconstruction of higher-stress-bearing abdominal walls.

A New Detergent for the Effective Decellularization of Bovine and Porcine Pericardia.

Human and animal pericardia are among the most widely exploited materials suitable to repair damaged tissues in the cardiovascular surgery context. Autologous, xenogeneic (chemically treated) and homologous pericardia are largely utilized, but they do exhibit some crucial drawbacks. Any tissue treated with glutaraldehyde is known to be prone to calcification in vivo, lacks regeneration potential, has limited durability, and can result in cytotoxicity. Moreover, autologous tissues have limited availability. Decellularized biological tissues represent a promising alternative: decellularization removes cellular and nuclear components from native tissues and makes them suitable for repopulation by autologous cells upon implantation into the body. The present work aims to assess the effects of a new detergent, i.e., Tergitol, for decellularizing bovine and porcine pericardia. The decellularization procedure successfully removed cells, while preserving the histoarchitecture of the extracellular matrix. No cytotoxic effect was observed. Therefore, decellularized pericardia showed potential to be used as scaffold for cardiovascular tissue regeneration.

In Vitro Tissue Reconstruction Using Decellularized Pericardium Cultured with Cells for Ligament Regeneration.

Recent applications of decellularized tissues have included the ectopic use of their sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are fabricated with the desired functions to employ them to a target tissue. The aim of this study was to develop a 3D reconstruction method using a recellularized pericardium to overcome the difficulties in cell infiltration into tight and dense tissues, such as ligament and tendon tissues. Decellularized pericardial tissues were prepared using the high hydrostatic pressurization (HHP) and surfactant methods. The pericardium consisted of bundles of aligned fibers. The bundles were slightly disordered in the surfactant decellularization method compared to the HHP decellularization method. The mechanical properties of the pericardium were maintained after the HHP and surfactant decellularizations. The HHP-decellularized pericardium was rolled up into a cylindrical formation. Its mechanical behavior was similar to that of a porcine anterior cruciate ligament in tensile testing. NIH3T3, C2C12, and mesenchymal stem cells were adhered with elongation and alignment on the HHP- and surfactant-decellularized pericardia, with dependences on the cell type and decellularization method. When the recellularized pericardium was rolled up into a cylinder formation and cultured by hanging circulation for 2 days, the cylinder formation and cellular elongation and alignment were maintained on the decellularized pericardium, resulting in a layer structure of cells in a cross-section. According to these results, the 3D-reconstructed decellularized pericardium with cells has the potential to be an attractive alternative to living tissues, such as ligament and tendon tissues.

Comparison on the properties of bovine pericardium and porcine pericardium used as leaflet materials of transcatheter heart valve.

BACKGROUND: In order to obtain the smaller delivery diameter, porcine pericardium had been used as a substitute material of bovine pericardium for the leaflet materials of transcatheter heart valve (THV). However, the differences between them had not been fully studied. Therefore, this study compared the microstructure, biochemical and mechanical properties of two materials and hydrodynamics of THV made by the two materials in detail. METHODS: In this study, firstly, the microstructure of pericardium was analyzed by staining and scanning electron microscope; secondly, the biochemical properties of pericardium after different processes were compared by heat shrinkage temperature test, free amino and carboxyl concentration test, enzyme degradation test, subcutaneous implantation calcification analysis in rats; finally, the mechanical properties were evaluated by uniaxial tensile test before and after the pericardium being crimped, and then, the hydrodynamics of THV was studied according to the ISO5840 standard. RESULTS: Compared with bovine pericardium, after the same process, porcine pericardium showed a looser and tinier fiber bundle, a similar free carboxyl concentration, a lower resistance to enzyme degradation, a significantly lower calcification, bearing capacity and damage after being crimped, a better hydrodynamic and adaption with lower cardiac output and deformation of implantation position. Meanwhile the dehydration process of pericardium almost had preserved all the biochemical advantages of two materials. CONCLUSION: In this study, porcine and bovine pericardium showed some significant differences in biochemical, mechanical properties and hydrodynamics. According to the results, it was presumed that the thinner porcine pericardium might be more suitable for THV of right heart system. Meanwhile, more attention should be taken for the calcification of THV made by the bovine pericardium.

In Vitro Evaluation of Acellular Collagen Matrices Derived from Porcine Pericardium: Influence of the Sterilization Method on Its Biological Properties.

The aim of this study were characterize acellular collagen matrices derived from porcine pericardium (PP) and to evaluate their properties after sterilization by ethylene oxide and gamma ray. PP matrices were subjected to alkaline hydrolysis (AH), and samples were characterized for biological stability, membrane thickness measurements, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Subsequently, the matrices were frozen, lyophilized and sterilized by ethylene oxide or gamma radiation. For in vitro assays, CHO-K1 cell culture was used and evaluated for cytotoxicity, clonogenic survival assay, genotoxicity and mutagenicity. Analysis of variance (ANOVA) was used, followed by Dunnett's post-test, with a significance level of 5%. After AH, there was no significant change in matrix thickness. The relative biodegradability of the material after implantation was observed. Morphology and dimensions had small changes after AH. As for cell viability, none of the tested matrices showed a statistically significant difference (p > 0.05; Dunnett) regardless of the sterilization method. Furthermore, it was found that PP matrices did not interfere with the proliferation capacity of CHO-K1 cells (p > 0.05; Dunnett). As for genotoxicity, when sterilized with ethylene oxide (NP, P12 and P24), it showed genotoxic potential, but it was not genotoxic when sterilized by gamma radiation. No mutagenic effects were observed in either group. PP-derived collagen matrices hydrolyzed at different times were not cytotoxic. It is concluded that the best method of sterilization is through gamma radiation, since no significant changes were observed in the properties of the PP matrices.

Hybrid membranes for the production of blood contacting surfaces: physicochemical, structural and biomechanical characterization.

BACKGROUND: Due to the shortage of organs' donors that limits biological heart transplantations, mechanical circulatory supports can be implanted in case of refractory end-stage heart failure to replace partially (Ventricular Assist Device, VAD) or completely (Total Artificial Heart, TAH) the cardiac function. The hemocompatibility of mechanical circulatory supports is a fundamental issue that has not yet been fully matched; it mostly depends on the nature of blood-contacting surfaces. METHODS: In order to obtain hemocompatible materials, a pool of hybrid membranes was fabricated by coupling a synthetic polymer (polycarbonate urethane, commercially available in two formulations) with a decellularized biological tissue (porcine pericardium). To test their potential suitability as candidate materials for realizing the blood-contacting surfaces of a novel artificial heart, hybrid membranes have been preliminarily characterized in terms of physicochemical, structural and mechanical properties. RESULTS: Our results ascertained that the hybrid membranes are properly stratified, thus allowing to expose their biological side to blood and their polymeric surface to the actuation system of the intended device. From the biomechanical point of view, the hybrid membranes can withstand deformations up to more than 70 % and stresses up to around 8 MPa. CONCLUSIONS: The hybrid membranes are suitable for the construction of the ventricular chambers of innovative mechanical circulatory support devices.

The Early Fragmentation of a Bovine Dermis-Derived Collagen Barrier Membrane Contributes to Transmembraneous Vascularization-A Possible Paradigm Shift for Guided Bone Regeneration.

Collagen-based barrier membranes are an essential component in Guided Bone Regeneration (GBR) procedures. They act as cell-occlusive devices that should maintain a micromilieu where bone tissue can grow, which in turn provides a stable bed for prosthetic implantation. However, the standing time of collagen membranes has been a challenging area, as native membranes are often prematurely resorbed. Therefore, consolidation techniques, such as chemical cross-linking, have been used to enhance the structural integrity of the membranes, and by consequence, their standing time. However, these techniques have cytotoxic tendencies and can cause exaggerated inflammation and in turn, premature resorption, and material failures. However, tissues from different extraction sites and animals are variably cross-linked. For the present in vivo study, a new collagen membrane based on bovine dermis was extracted and compared to a commercially available porcine-sourced collagen membrane extracted from the pericardium. The membranes were implanted in Wistar rats for up to 60 days. The analyses included well-established histopathological and histomorphometrical methods, including histochemical and immunohistochemical staining procedures, to detect M1- and M2-macrophages as well as blood vessels. Initially, the results showed that both membranes remained intact up to day 30, while the bovine membrane was fragmented at day 60 with granulation tissue infiltrating the implantation beds. In contrast, the porcine membrane remained stable without signs of material-dependent inflammatory processes. Therefore, the bovine membrane showed a special integration pattern as the fragments were found to be overlapping, providing secondary porosity in combination with a transmembraneous vascularization. Altogether, the bovine membrane showed comparable results to the porcine control group in terms of biocompatibility and standing time. Moreover, blood vessels were found within the bovine membranes, which can potentially serve as an additional functionality of barrier membranes that conventional barrier membranes do not provide.