Effects of disinfection and sterilization on the dimensional changes and mechanical properties of 3D printed surgical guides for implant therapy - pilot study.

BACKGROUND: The purpose of this research was to investigate the effects of disinfection and three different sterilization methods on the dimensional changes and mechanical properties of three-dimensional (3D) printed surgical guide for implant therapy. The objective was to assess the effects of sterilization procedures in 3D printed drill guide templates with destructive and non-destructive material testing. METHODS: Fifteen identical drill guide templates were produced using a 3D printer. The surgical guides were classified into five groups: three controls, three disinfected (4% Gigasept®, 60 min), three plasma sterilized, three autoclave sterilized (+ 1 bar, 121 °C, 20 min), and three autoclave sterilized (+ 2 bar, 134 °C, 10 min). The templates were digitalized with a Steinbichler SCAN ST 3D scanner. Length was measured under an SZX16 stereomicroscope. A scanning electron microscope was used to study the surface morphology of the drill templates. The hardness, and flexural and compressive strength were measured to assess any changes in the physical characteristics of the material caused by sterilization. The drill guide templates were also examined with a Dage XiDAT 6600 X-ray. During the X-ray examinations, the following parameters were used: 100 kV voltage, 128 AVG averaging, 0.8 W power. One-way analysis of variance (ANOVA) was used to detect the difference between groups. RESULTS: Evaluation of the hardness measurements of the various specimens shows that the hardness of the material was not changed by the plasma sterilization (p = 0.0680), steam sterilization on 121 °C (p = 0.6033) or disinfection process (p = 0.1399). The statistical analysis revealed significant difference in hardness strength of the autoclave sterilized (134 °C) specimens (p = 0.0002). There was no significant difference between the goups regarding the scanning electron microscopic and stereomicroscopic examinations. There was no significant difference regarding the X-ray visibility of the templates to the effect of the disinfection (p = 0.7844), plasma sterilization (p = 0.4091) and steam sterilization on 121 °C (p = 0.9277) and steam sterilization on 131 °C (p = 0.093). The effect of the sterilization was the same in case of both flexural and compressive strength of the material. CONCLUSIONS: Our findings indicate that plasma sterilization and steam sterilization at 121 °C were both suitable for sterilizing the tested 3D printed surgical guides.

Review: the potential impact of surface crystalline states of titanium for biomedical applications.

In many biomedical applications, titanium forms an interface with tissues, which is crucial to ensure its long-term stability and safety. In order to exert control over this process, titanium implants have been treated with various methods that induce physicochemical changes at nano and microscales. In the past 20 years, most of the studies have been conducted to see the effect of topographical and physicochemical changes of titanium surface after surface treatments on cells behavior and bacteria adhesion. In this review, we will first briefly present some of these surface treatments either chemical or physical and we explain the biological responses to titanium with a specific focus on adverse immune reactions. More recently, a new trend has emerged in titanium surface science with a focus on the crystalline phase of titanium dioxide and the associated biological responses. In these recent studies, rutile and anatase are the major two polymorphs used for biomedical applications. In the second part of this review, we consider this emerging topic of the control of the crystalline phase of titanium and discuss its potential biological impacts. More in-depth analysis of treatment-related surface crystalline changes can significantly improve the control over titanium/host tissue interface and can result in considerable decreases in implant-related complications, which is currently a big burden on the healthcare system.

[Pliability and deflection of diagnostic catheters]. / Szívkatéterek hajlékonysága, meghajlítása.

INTRODUCTION: The cardiac catheter is an intravascular catheter, which is introduced or implanted into the heart for diagnostic or therapeutic reasons. The catheters may break or king during their introduction and/or removal. AIM: The aim of the authors was to study the pliability of two catheters with the same material but different diameters according to the Food and Drug Administration's recommendation. METHOD: The bending points, diameter decrease, deflection, and their correlation and dependence on the distance from the tip, as well as the influence of the initial diameter of the catheters were determined. The bending of catheters was performed on 9 bending points (120-280 mm from the tip by 20 mm) on 16 gauges with different radius (10-2.5 mm by 0.5 mm). RESULTS: A linear dependency between the diameter decrease and deflection was observed, which was independent from the placement of the measurement in both catheters examined. The larger initial diameter had significant (p = 0.05) greater diameter decrease than the smaller, but the curves characteristic of the diameter decrease and deflection were similar. CONCLUSIONS: The applied method seems to be useful for the examination of weak points of cardiac catheters.

Interaction of intraluminal tissue and coronary sinus lead stabilized with stent placement.

INTRODUCTION: The aim of our investigation was to examine the intraluminal interaction of the vascular tissue and the implanted coronary sinus lead stabilized with stent on two human hearts removed before transplantation. METHODS AND RESULTS: The coronary sinus lumen was sectioned under operational microscope and opened carefully. The leads and stents were found separately positioned beside each other completely covered by an intact intimal tissue layer. No sign of occluding proliferative tissue was observed. CONCLUSION: Stent fixation technique and extraction of the CS lead in our cases did not have any particular damaging effect on the vascular system.

Methods for examination an explanted coronary sinus lead stabilized with a coronary stent.

The aim of our investigation was to test the suitability of a novel method for the analysis of the integrity of an explanted pacemaker lead stabilized by a stent. A coronary sinus lead has been explanted 27 months after implantation and has been examined by optical-, confocal-, x-ray-, and scanning electron microscopy. Several surface injuries were found on the insulation. Based on the surface characteristics, it is possible to define and differentiate the source of damages as well as to measure the extent of injuries. Impedance of the explanted lead has also been measured and electronic integrity has been verified.

Enhancement of Hydrophilicity of Nano-Pitted TiO2 Surface Using Phosphoric Acid Etching.

Our research group developed a novel nano-pitted (NP) TiO2 surface on grade 2 titanium that showed good mechanical, osteogenic, and antibacterial properties; however, it showed weak hydrophilicity. Our objective was to develop a surface treatment method to enhance the hydrophilicity of the NP TiO2 surface without the destruction of the nano-topography. The effects of dilute and concentrated orthophosphoric (H3PO4) and nitric acids were investigated on wettability using contact angle measurement. Optical profilometry and atomic force microscopy were used for surface roughness measurement. The chemical composition of the TiO2 surface and the oxidation state of Ti was investigated using X-ray photoelectron spectroscopy. The ccH3PO4 treatment significantly increased the wettability of the NP TiO2 surfaces (30°) compared to the untreated control (88°). The quantity of the absorbed phosphorus significantly increased following ccH3PO4 treatment compared to the control and caused the oxidation state of titanium to decrease (Ti4+ → Ti3+). Owing to its simplicity and robustness the presented surface treatment method may be utilized in the industrial-scale manufacturing of titanium implants.

BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases.

In this study, we investigate the cardiotoxic effects of the well-known cytostatic agent imatinib mesylate (Gleevec), and presented evidence for the cardioprotective effect of BGP-15 which is a novel insulin sensitizer. The cardiotoxic effect of imatinib mesylate was assessed in Langendorff rat heart perfusion system. The cardiac high-energy phosphate levels (creatine phosphate (PCr) and ATP) were monitored in situ by (31)P NMR spectroscopy. The protein oxidation, lipid peroxidation, and the activation of signaling pathways were determined from the freeze-clamped hearts. Prolonged treatment of the heart with imatinib mesylate (20 mg/kg) resulted in cardiotoxicity, which were characterized by the depletion of high-energy phosphates (PCr and ATP), and significantly increased protein oxidation and lipid peroxidation. Imatinib mesylate treatment-induced activation of MAP kinases (including ERK1/2, p38, and JNK) and the phosphorylation of Akt and GSK-3beta. BGP-15 (200 µM) prevented the imatinib mesylate-induced oxidative damages, attenuated the depletion of high-energy phosphates, altered the signaling effect of imatinib mesylate by preventing p38 MAP kinase and JNK activation, and induced the phosphorylation of Akt and GSK-3beta. The suppressive effect of BGP-15 on p38 and JNK activation could be significant because these kinases contribute to the cell death and inflammation in the isolated perfused heart.

Nonlinear fiber-bundle-cells-based phenomenological modeling of human tissue samples.

Certain assemblies of fibers, called fiber bundles, play a crucial role in the statistical macroscale properties of fibrous structures like natural or artificial materials. Based on the concept of using idealized statistical fiber bundle cells (FBCs) as model elements, the software named FiberSpace was developed by us earlier for the phenomenological modeling of the tensile test process of real fibrous structures. The model fibers of these FBCs had been considered linear elastic, which was suitable for modeling certain textiles and composites. However, the biological tissues are multilevel structures with fiber-like building elements on every structural level where the fiber elements on the dominant level are statistical bundles of elementary fibers. Hence, their modeling required us to introduce model fibers of nonlinear mechanical behavior and derive the proper mathematical formulas for the calculation of the expected tensile force processes of the FBCs. Accordingly, we developed a new version of FiberSpace. The proposed nonlinear FBCs-based modeling method is essentially phenomenological that decomposes the measured and averaged stress-strain curve into the weighted sum of the responses of different idealized nonlinear FBCs. However, this decomposition can give certain information about the fibrous structure and some details of its damage and failure sub-processes. A special application of nonlinear E-bundles, where the measured stress-strain curve is expanded into a product-function series, may give another type of description for the failure process and can be applied to single measurements of structured failure process containing significant peaks and drops as well. The fitted phenomenological FBC models provide a decomposition of the measured force-strain curve, which enables to construct informative damage and failure maps. The applicability of the phenomenological modeling method and the fitting procedure is demonstrated with the tensile test data of some human and animal tissues, such as facial nerves and tendons.

Prevalent role of Akt and ERK activation in cardioprotective effect of Ca(2+) channel- and beta-adrenergic receptor blockers.

We studied cardioprotective as well as Akt and extracellular signal-activated kinase (ERK) activating effect of a Ca(2+) antagonist and a beta-adrenergic receptor blocker during ischemia-reperfusion, and compared these properties of the substances with that of a poly(ADP-ribose) polymerase (PARP) inhibitor used as a positive control throughout the experiments. Langendorff-perfused isolated rat hearts were subjected to 25 min global ischemia followed by 45 min reperfusion, and recovery of energy metabolism as well as functional cardiac parameters were monitored. Although to varying extents, all substances improved recovery of creatine phosphate, ATP, intracellular pH, and reutilization of inorganic phosphate. These favorable changes were accompanied by improved recovery of heart function parameters and reduced infarct size. In addition and again to varying extents, all studied substances decreased oxidative damage (lipid peroxidation and protein oxidation), and activated Akt, glycogen synthase kinase (GSK)-3beta, and ERK1/2. Correlation between cardioprotective and kinase activating effectivity of the compounds proved to be statistically significant. Physiological significance of these kinase activations was established by demonstrating that inhibition of Akt by LY294002 and ERK1/2 by PD98059 compromised the cardioprotective effect of all the substances studied. In conclusion, we demonstrated for the first time that activation of phosphatidylinositol-3-kinase (PI-3K)-Akt and ERK2 pathways significantly contributed to cardioprotective effects of a Ca(2+) antagonist and a beta-adrenergic receptor blocker. Furthermore, we found a strong correlation between cardioprotective and kinase-activating potencies of the substances studied (Verapamil, Metoprolol and two PARP inhibitors), which indicated the potentiality of these kinases as drug-targets in the therapy of ischemic heart disease.

Osteogenic nanostructured titanium surfaces with antibacterial properties under conditions that mimic the dynamic situation in the oral cavity.

The study aim was to assess the impact of different surface nanofeatures on otherwise smooth titanium surfaces on bacterial adhesion as well as on their osteogenic potential. Bacterial adhesion was assessed in the presence of saliva under static and dynamic conditions to approximate both sub- and supragingival conditions in the oral cavity as the gingival seal will be affected by implantation. The ultimate goal was to develop a surface that will reduce biofilm formation but still support osseointegration in vivo. To this end nanotubular or nanopitted surfaces were created on electropolished titanium via electrochemical anodization procedures. Sandblasted/acid etched surfaces (SBAE) were used as a microrough reference. Bacterial adhesion was studied using saliva-precoated samples with S. sanguinis as a typical early colonizer of the oral cavity; osteogenic differentiation was assessed with human bone marrow stromal cells. While bacterial adhesion was reduced on all microsmooth surfaces to an average of 17% surface coverage compared to 61% on SBAE under static conditions, under dynamic conditions the nanopitted surface had a significant impact on bacterial adhesion. Here fluid flow removed all bacteria. By comparison, the reduction on the nanotubular surface was only similar to that of the SBAE reference. We hypothesise the underlying cause to be an effect of the surface morphology on the structure and composition of the saliva precoating that reduces its stability, giving rise to a self-cleaning effect. In addition, no negative influence on the osteogenic potential of the nanopitted surface could be determined by alkaline phosphatase activity, mineralization behaviour or gene expression; it remained on a par with the tissue culture plastic control. Thus, nanopitting seems to be a promising surface treatment candidate for dental implants to reduce infection related complications without compromising the implant integration.

Investigation of the mechanical and chemical characteristics of nanotubular and nano-pitted anodic films on grade 2 titanium dental implant materials.

OBJECTIVE: The objective of this study was to investigate the reproducibility, mechanical integrity, surface characteristics and corrosion behavior of nanotubular (NT) titanium oxide arrays in comparison with a novel nano-pitted (NP) anodic film. METHODS: Surface treatment processes were developed to grow homogenous NT and NP anodic films on the surface of grade 2 titanium discs and dental implants. The effect of process parameters on the surface characteristics and reproducibility of the anodic films was investigated and optimized. The mechanical integrity of the NT and NP anodic films were investigated by scanning electron microscopy, surface roughness measurement, scratch resistance and screwing tests, while the chemical and physicochemical properties were investigated in corrosion tests, contact angle measurement and X-ray photoelectron spectroscopy (XPS). RESULTS AND DISCUSSION: The growth of NT anodic films was highly affected by process parameters, especially by temperature, and they were apt to corrosion and exfoliation. In contrast, the anodic growth of NP film showed high reproducibility even on the surface of 3-dimensional screw dental implants and they did not show signs of corrosion and exfoliation. The underlying reason of the difference in the tendency for exfoliation of the NT and NP anodic films is unclear; however the XPS analysis revealed fluorine dopants in a magnitude larger concentration on NT anodic film than on NP surface, which was identified as a possible causative. Concerning other surface characteristics that are supposed to affect the biological behavior of titanium implants, surface roughness values were found to be similar, whereas considerable differences were revealed in the wettability of the NT and NP anodic films. CONCLUSION: Our findings suggest that the applicability of NT anodic films on the surface of titanium bone implants may be limited because of mechanical considerations. In contrast, it is worth to consider the applicability of nano-pitted anodic films over nanotubular arrays for the enhancement of the biological properties of titanium implants.

Chemical etching of nitinol stents.

At present the main cause of death originates from cardiovascular diseases. Primarily the most frequent cause is vessel closing thus resulting in tissue damage. The stent can help to avoid this. It expands the narrowed vessel section and allows free blood flow. The good surface quality of stents is important. It also must have adequate mechanical characteristics or else it can be damaged which can easily lead to the fracture of the implant. Thus, we have to consider the importance of the surface treatment of these implants. In our experiments the appropriate design was cut from a 1.041 mm inner diameter and 0.100 mm wall thickness nitinol tube by using Nd:YAG laser device. Then, the stent was subjected to chemical etching. By doing so, the burr created during the laser cutting process can be removed and the surface quality refined. In our research, we changed the time of chemical etching and monitored the effects of this parameter. The differently etched stents were subjected to microscopic analysis, mass measurement and in vivo environment tests. The etching times that gave suitable surface and mechanical features were identified.

Ablation time efficiency and lesion volume - in vitro comparison of 4 mm, non irrigated, gold- and platinum-iridium-tip radiofrequency ablation catheters.

PURPOSE: We investigated the development of in vitro lesion formation in relation to ablation time and power delivery using 4-mm, non-irrigated, platinum-iridium (Pt/Ir), and gold-tip catheters. METHODS: Radiofrequency catheter ablation was performed on porcine liver preparations in a 5-60-s time range with 5 s increments applied at different lesion sites. Each series was repeated four times for both catheters. The lesion volume, the delivered energy, and the ablation power curves were analyzed in 96 ablations. RESULTS: The delivered energy was higher and the lesion volume was significantly larger when using a gold-tip catheter. The lesion volume that was created with the Pt/Ir-tip electrode within 60 s was created after a shorter 40 s ablation period with the gold-tip electrode (Au, 40 s, 345 ± 75 mm(3) vs. Pt/Ir, 60 s, 328 ± 30 mm(3)). CONCLUSION: The gold-tip catheters had a lower tip temperature resulting in higher energy delivery due to the better thermo-conductivity of the gold alloy. A significantly higher lesion volume and a faster lesion creation were found for gold catheters as compared to Pt/Ir catheters. Gold-tip catheters can create the same adequate lesion within 33.3 % less ablation time due to the higher values of delivered energy as compared to those observed with the use of Pt/Ir catheters.

Antioxidant and anti-inflammatory effects in RAW264.7 macrophages of malvidin, a major red wine polyphenol.

BACKGROUND: Red wine polyphenols can prevent cardiovascular and inflammatory diseases. Resveratrol, the most extensively studied constituent, is unlikely to solely account for these beneficial effects because of its rather low abundance and bioavailability. Malvidin is far the most abundant polyphenol in red wine; however, very limited data are available about its effect on inflammatory processes and kinase signaling pathways. METHODS FINDINGS: The present study was carried out by using RAW 264.7 macrophages stimulated by bacterial lipopolysaccharide in the presence and absence of malvidin. From the cells, activation of nuclear factor-kappaB, mitogen-activated protein kinase, protein kinase B/Akt and poly ADP-ribose polymerase, reactive oxygen species production, mitogen-activated protein kinase phosphatase-1 expression and mitochondrial depolarization were determined. We found that malvidin attenuated lipopolysaccharide-induced nuclear factor-kappaB, poly ADP-ribose polymerase and mitogen-activated protein kinase activation, reactive oxygen species production and mitochondrial depolarization, while upregulated the compensatory processes; mitogen-activated protein kinase phosphatase-1 expression and Akt activation. CONCLUSIONS: These effects of malvidin may explain the previous findings and at least partially account for the positive effects of moderate red wine consumption on inflammation-mediated chronic maladies such as obesity, diabetes, hypertension and cardiovascular disease.

Freeze-dried human serum albumin improves the adherence and proliferation of mesenchymal stem cells on mineralized human bone allografts.

Mineralized scaffolds are widely used as bone grafts with the assumption that bone marrow derived cells colonize and remodel them. This process is slow and often unreliable so we aimed to improve the biocompatibility of bone grafts by pre-seeding them with human mesenchymal stem cells from either bone marrow or dental pulp. Under standard cell culture conditions very low number of seeded cells remained on the surface of freeze-dried human or bovine bone graft or hydroxyapatite. Coating the scaffolds with fibronectin or collagen improved seeding efficiency but the cells failed to grow on the surface until the 18th day. In contrast, human albumin was a very potent facilitator of both seeding and proliferation on allografts which was further improved by culturing in a rotating bioreactor. Electron microscopy revealed that cells do not form a monolayer but span the pores, emphasizing the importance of pore size and microstructure. Albumin coated bone chips were able to unite a rat femoral segmental defect, while uncoated ones did not. Micro-hardness measurements confirmed that albumin coating does not influence the physical characteristics of the scaffold, so it is possible to introduce albumin coating into the manufacturing process of lyophilized bone allografts.

Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion.

Pituitary adenylate cyclase activating polypeptide (PACAP) is known for its potent neuroprotective effects, including the retinoprotective actions in several types of retinal injuries. We have shown earlier that PACAP treatment causes activation of protective pathways and inhibition of pro-apoptotic signaling in excitotoxic retinal lesions. The aim of the present study was to gain insight into the in vivo protective mechanism of PACAP in retinal hypoperfusion injury induced by bilateral common carotid artery occlusion (BCCAO). Rats underwent BCCAO and received intravitreal PACAP (PACAP38) treatment. We investigated the activation level of the protective Akt pathway as well as the different mitogen activated protein kinases (MAPKs) by Western blot analysis and the expression of cytokines using a cytokine array kit. We found that PACAP treatment alone did not influence the phosphorylation of Akt or the MAPKs, but decreased the hypoperfusion-induced activation of both p38MAPK and JNK and increased the activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile was dramatically changed after BCCAO, with most cytokines and chemokines showing an increase, which was attenuated by PACAP (such as CINC, CNTF, fractalkine, sICAM, IL-1, LIX, Selectin, MIP-1, RANTES and TIMP-1). In addition, PACAP increased the expression of VEGF and thymus chemokine. The present results provide further insight into the neuroprotective mechanism induced by PACAP in ischemic retinal injuries, showing that PACAP ameliorates hypoperfusion injury involving Akt, MAPK pathways and anti-inflammatory actions.