Evaluation of In Vivo Biocompatibility in Preclinical Studies of a Finger Implant Medical Device Correlated with Mechanical Properties and Microstructure.

The aim of the experiment was to evaluate the biocompatibility of four 3D-printed biomaterials planned for use in the surgical treatment of finger amputees: Ti-6Al-4 V (Ti64), ZrO2-Al2O3 ceramic material (ATZ20), and osteoconductive (anodized Ti64) and antibacterial (Hydroxyapatite, HAp) coatings that adhere well to materials dedicated to finger bone implants. The work concerns the correlation of mechanical, microstructural, and biological properties of dedicated materials. Biological tests consisted of determining the overall cytotoxicity of the organism on the basis of in vivo tests carried out in accordance with the ISO 10993-6 and ISO 10993-11 standards. Clinical observations followed by diagnostic examinations, histopathological evaluation, and biochemical characterization showed no significant differences between control and tested groups of animals. The wound healed without complication, and no pathological effects were found. The wear test showed the fragility of the hydroxyapatite thin layer and the mechanical stability of the zirconia-based ceramic substrate. Electron microscopy observations revealed the layered structure of tested substrates and coatings.

Cytokine Profile in Development of Glioblastoma in Relation to Healthy Individuals.

Cytokines play an essential role in the control of tumor cell development and multiplication. However, the available literature provides ambiguous data on the involvement of these proteins in the formation and progression of glioblastoma (GBM). This study was designed to evaluate the inflammatory profile and to investigate its potential for the identification of molecular signatures specific to GBM. Fifty patients aged 66.0 ± 10.56 years with newly diagnosed high-grade gliomas and 40 healthy individuals aged 71.7 ± 4.9 years were included in the study. White blood cells were found to fall within the referential ranges and were significantly higher in GBM than in healthy controls. Among immune cells, neutrophils showed the greatest changes, resulting in elevated neutrophil-to-lymphocyte ratio (NLR). The neutrophil count inversely correlated with survival time expressed by Spearman's coefficient rs = -0.359 (p = 0.010). The optimal threshold values corresponded to 2.630 × 103/µL for NLR (the area under the ROC curve AUC = 0.831, specificity 90%, sensitivity 76%, the relative risk RR = 7.875, the confidence intervals 95%CI 3.333-20.148). The most considerable changes were recorded in pro-inflammatory cytokines interleukin IL-1ß, IL-6, and IL-8, which were approx. 1.5-2-fold higher, whereas tumor necrosis factor α (TNFα) and high mobility group B1 (HMGB1) were lower in GBM than healthy control (p < 0.001). The results of the ROC, AUC, and RR analysis of IL-1ß, IL-6, IL-8, and IL-10 indicate their high diagnostics potential for clinical prognosis. The highest average RR was observed for IL-6 (RR = 2.923) and IL-8 (RR = 3.151), which means there is an approx. three-fold higher probability of GBM development after exceeding the cut-off values of 19.83 pg/mL for IL-6 and 10.86 pg/mL for IL-8. The high values of AUC obtained for the models NLR + IL-1ß (AUC = 0.907), NLR + IL-6 (AUC = 0.908), NLR + IL-8 (AUC = 0.896), and NLR + IL-10 (AUC = 0.887) prove excellent discrimination of GBM patients from healthy individuals and may represent GBM-specific molecular signatures.

Tribological Performance of Anti-Wear Coatings on Tools for Forming Aluminium Alloy Sheets Used for Producing Pull-Off Caps.

Ensuring adequate reliability of the production process of packaging closures has made it necessary to study the effect of annealing and varnishing variants on the strength and structural properties of the stock material. As a test material, EN AW-5052-H28 aluminium alloy sheets with a thickness of 0.21 mm were used. The surface treatment of the test material involved varnishing the sheet metal surface using various varnishes and soaking the sheet metal. The coefficient of friction and the abrasion resistance of the coatings were determined using the T-21 ball-and-disc tribotester. The tested sheets were subjected to tribological analysis by the T-05 roller-block tribotester using countersamples made of Caldie and Sverker 21 tool steels. The results of the tests showed differences in mechanical and structural properties depending on the method of sample preparation. Based on the test results, significant differences in the adhesion of anti-wear coatings were found. The results revealed that the most favourable friction conditions are provided by the CrN coating. The (AlTi)N interlayer in the (AlTi)N/(AlCr)N coating adheres to the substrate over the entire tested area and no detachment from its surface was observed, which proves good bonding at the substrate/coating interface. The tested AlTiN/TiAlSiXN coating is characterised by a more homogeneous, compact microstructure compared to the (AlTi)N/(AlCr)N coating.

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. METHODS: The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. RESULTS: Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 and HR 1.34, 95% CI 1.10-1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). CONCLUSIONS: Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.

Hemocompatibile Thin Films Assessed under Blood Flow Shear Forces.

The aim of this study was to minimize the risk of life-threatening thromboembolism in the ventricle through the use of a new biomimetic heart valve based on metal-polymer composites. Finite volume element simulations of blood adhesion to the material were carried out, encompassing radial flow and the cone and plane test together with determination of the effect of boundary conditions. Both tilt-disc and bicuspid valves do not have optimized blood flow due to their design based on rigid valve materials (leaflet made of pyrolytic carbon). The main objective was the development of materials with specific properties dedicated to contact with blood. Materials were evaluated by dynamic tests using blood, concentrates, and whole human blood. Hemostability tests under hydrodynamic conditions were related to the mechanical properties of thin-film materials obtained from tribological tests. The quality of the coatings was high enough to avoid damage to the coating even as they were exposed up to maximum loading. Analysis towards blood concentrates of the hydrogenated carbon sample and the nitrogen-doped hydrogenated carbon sample revealed that the interaction of the coating with erythrocytes was the strongest. Hemocompatibility evaluation under hydrodynamic conditions confirmed very good properties of the developed coatings.

Prognostic Values of Combined Ratios of White Blood Cells in Glioblastoma: A Retrospective Study.

In some malignant tumours, the changes in neutrophil counts in relation to other blood cells are connected with unfavourable prognosis. Nevertheless, the prognostic value of the combinations of the haematological components in glioblastoma (GBM) remains under dispute. The clinical significance of the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) was investigated in our study. We retrospectively studied 358 patients (males n = 195; females n = 163) aged 59.9 ± 13.5 yrs with newly diagnosed glioma and admitted to the Neurosurgery Centre. Routine blood tests and clinical characteristics were recorded within the first hour of hospital admission. The inflammatory variables: NLR, SII and SIRI exceeded the reference values and were significantly elevated in Grade 3 and Grade 4 tumour. The Cox model analysis showed that the age ≥ 63 years, NLR ≥ 4.56 × 103/µL, SII ≥ 2003 × 103/µL and SIRI ≥ 3.03 × 103/µL significantly increased the risk of death in Grade 4 tumour patients. In the inflammatory variables, NLR demonstrated the highest impact on the survival time (HR 1.56; 95% CI 1.145-2.127; p = 0.005). In the first Polish study including GBM patients, the age in relation to simple parameters derived from complete blood cell count were found to have prognostic implications in the survival rate.

Inflammatory Predictors of Prognosis in Patients with Traumatic Cerebral Haemorrhage: Retrospective Study.

We aimed to evaluate the relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammation index (SII), and Glasgow Coma Scale (GCS) score in patients with traumatic intracerebral haemorrhage (TICH). We retrospectively investigated 95 patients with TICH hospitalised at the Neurosurgery Department in Zielona Gora from January 2017 to March 2021. Routine blood tests were performed 5 h after injury. NRL and SII were significantly higher in patients with GCS ≤ 8 than patients with GCS > 8 and exceeded reference values in 95% of patients. GCS was inversely correlated with NLR and SII. Receiver operating characteristic (ROC) analysis confirmed the value of NLR and SII regarding GCS score; Area Under the Curve (AUC) 0.748, 95% Confidence Interval (CI) 0.615-0.880. An optimised NLR cut-off value of 0.154 was identified with a sensitivity of 0.90 and specificity of 0.56. The value of SII regarding GCS was confirmed with ROC curves; AUC 0.816, 95% CI 0.696-0.935. An optimised NLR cut-off value of 0.118 was identified with a sensitivity of 0.95 and specificity of 0.57. NLR and SII are significantly related to GCS scores and are promising predictors of clinical prognosis in TICH patients.

Biocompatibility testing of composite biomaterial designed for a new petal valve construction for pulsatile ventricular assist device.

This paper presents the results of biocompatibility testing performed on several biomaterial variants for manufacturing a newly designed petal valve intended for use in a pulsatile ventricular assist device or blood pump. Both physical vapor deposition (PVD) and plasma-enhanced chemical vapor deposition (PECVD) were used to coat titanium-based substrates with hydrogenated tetrahedral amorphous carbon (ta-C:H) or amorphous hydrogenated carbon (a-C:H and a-C:H, N). Experiments were carried out using whole human blood under arterial shear stress conditions in a cone-plate analyzer (ap. 1800 1/s). In most cases, tested coatings showed good or very good haemocompatibility. Type a-C:H, N coating proved to be superior in terms of activation, risk of aggregation, and the effects of generating microparticles of apoptotic origin, and also demonstrated excellent mechanical properties. Therefore, a-C:H, N coatings were selected for further in vivo studies. In vivo animal studies were carried out according to the ISO 10993 standard. Intradermal reactivity was assessed in three rabbits and sub-acute toxicity and local effects after implantation were examined in 12 rabbits. Based on postmortem examination, no organ failure or wound tissue damage occurred during the required period of observation. In summary, our investigations demonstrated high biocompatibility of the biomaterials in relation to thrombogenicity, toxicity, and wound healing. Prototypes of the petal valves were manufactured and mounted on the pulsatile ventricular assist device. Hydrodynamic features and impact on red blood cells (hemolysis) as well as coagulation (systemic thrombogenicity) were assessed in whole blood.

Antibacterial Optimization of Highly Deformed Titanium Alloys for Spinal Implants.

The goal of the work was to develop materials dedicated to spine surgery that minimized the potential for infection originating from the transfer of bacteria during long surgeries. The bacteria form biofilms, causing implant loosening, pain and finally, a risk of paralysis for patients. Our strategy focused both on improvement of antibacterial properties against bacteria adhesion and on wear and corrosion resistance of tools for spine surgery. Further, a ~35% decrease in implant and tool dimensions was expected by introducing ultrahigh-strength titanium alloys for less-invasive surgeries. The tested materials, in the form of thin, multi-layered coatings, showed nanocrystalline microstructures. Performed direct-cytotoxicity studies (including lactate dehydrogenase activity measurement) showed that there was a low probability of adverse effects on surrounding SAOS-2 (Homo sapiens bone osteosarcoma) cells. The microbiological studies (e.g., ISO 22196 contact tests) showed that implanting Ag nanoparticles into Ti/TixN coatings inhibited the growth of E. coli and S. aureus cells and reduced their adhesion to the material surface. These findings suggest that Ag-nanoparticles present in implant coatings may potentially minimize infection risk and lower inherent stress.

Surface modification of metallic materials designed for a new generation of artificial heart valves.

PURPOSE:: The main goal of this work was to develop haemocompatibile thin film materials dedicated to novel flexible mechanical heart valves intended for pulsatile ventricle assist devices. METHODS:: The studies performed have led to the selection of a material for the surface modification of the metallic scaffold. Haemocompatible, biofunctional, ultra-elastic, thin carbon-based coatings were proposed. The surface was designed to eliminate thrombogenic and microbial construction by a reduction in turbulence and sufficient washing of the biofunctional-adapted surfaces, thus allowing for extended use for temporary heart support. The article presents the influence of the mechanical properties of coatings and their influence on the haemocompatibility. In this study, we investigated a simplified model of the whole blood shear stress based on a cone and plate rotational viscometer. Several indices of platelet activation were analysed, including platelet and granulocyte-platelet aggregates, platelet activation markers and platelet-derived microparticles. RESULTS:: The shear stress induced a platelet aggregate count in the range from 2% to 30% of the CD61 positive cells. For polyurethane (PU), the average value of platelet aggregates was on the level of 7%. The analyses have demonstrated that the cytometric methods of the direct determination of platelet-derived microparticles in plasma are reproducible and reliable. Considering the generation of microparticles on the tested coatings under hydrodynamic conditions, the best properties were observed for the coating a-C:H,N. CONCLUSION:: The results indicate that a-C:H-based coatings with the thickness of 110 nm do not induce an immune response and do not influence the origin of platelet microparticle formation; thus, these type of coatings are the most promising for the parts which are planned to withstand blood contact under the high value of shear stress.

Influence of polyetheretherketone coatings on the Ti-13Nb-13Zr titanium alloy's bio-tribological properties and corrosion resistance.

Polyetheretherketone (PEEK) coatings of 70-90µm thick were electrophoretically deposited from a suspension of PEEK powder in ethanol on near-ß Ti-13Nb-13Zr titanium alloy. In order to produce good quality coatings, the composition of the suspension (pH) and optimized deposition parameters (applied voltage and time) were experimentally selected. The as-deposited coatings exhibited the uniform distribution of PEEK powders on the substrate. The subsequent annealing at a temperature above the PEEK melting point enabled homogeneous, semi-crystalline coatings with spherulitic morphology to be produced. A micro-scratch test showed that the coatings exhibited very good adhesion to the titanium alloy substrate. Coating delamination was not observed even up to a maximal load of 30N. The PEEK coatings significantly improved the tribological properties of the Ti-13Nb-13Zr alloy. The coefficient of friction was reduced from 0.55 for an uncoated alloy to 0.40 and 0.12 for a coated alloy in a dry sliding and sliding in Ringer's solution, respectively. The PEEK coatings exhibited excellent wear resistance in both contact conditions. Their wear rate was more than 200 times smaller compared with the wear rate of the uncoated Ti-13Nb-13Zr alloy. The obtained results indicate that electrophoretically deposited PEEK coatings on the near-ß titanium alloy exhibit very useful properties for their prospective tribological applications in medicine.

In vitro hemocompatibility on thin ceramic and hydrogel films deposited on polymer substrate performed in arterial flow conditions.

Hydrogel coatings were stabilized by titanium carbonitride a-C:H:Ti:N buffer layers deposited directly onto the polyurethane (PU) substrate beneath a final hydrogel coating. Coatings of a-C:H:Ti:N were deposited using a hybrid method of pulsed laser deposition (PLD) and magnetron sputtering (MS) under high vacuum conditions. The influence of the buffer a-C:H:Ti:N layer on the hydrogel coating was analysed by means of a multi-scale microstructure study. Mechanical tests were performed at an indentation load of 5 mN using Berkovich indenter geometry. Haemocompatible analyses were performed in vitro using a blood flow simulator. The blood-material interaction was analysed under dynamic conditions. The coating fabrication procedure improved the coating stability due to the deposition of the amorphous titanium carbonitride buffer layer.

Parylene coatings on stainless steel 316L surface for medical applications--mechanical and protective properties.

The mechanical and protective properties of parylene N and C coatings (2-20 µm) on stainless steel 316L implant materials were investigated. The coatings were characterized by scanning electron and confocal microscopes, microindentation and scratch tests, whereas their protective properties were evaluated in terms of quenching metal ion release from stainless steel to simulated body fluid (Hanks solution). The obtained results revealed that for parylene C coatings, the critical load for initial cracks is 3-5 times higher and the total metal ions release is reduced 3 times more efficiently compared to parylene N. It was thus concluded that parylene C exhibits superior mechanical and protective properties for application as a micrometer coating material for stainless steel implants.

Properties of chemically oxidized kininogens.

Kininogens are multifunctional proteins involved in a variety of regulatory processes including the kinin-formation cascade, blood coagulation, fibrynolysis, inhibition of cysteine proteinases etc. A working hypothesis of this work was that the properties of kininogens may be altered by oxidation of their methionine residues by reactive oxygen species that are released at the inflammatory foci during phagocytosis of pathogen particles by recruited neutrophil cells. Two methionine-specific oxidizing reagents, N-chlorosuccinimide (NCS) and chloramine-T (CT), were used to oxidize the high molecular mass (HK) and low molecular mass (LK) forms of human kininogen. A nearly complete conversion of methionine residues to methionine sulfoxide residues in the modified proteins was determined by amino acid analysis. Production of kinins from oxidized kininogens by plasma and tissue kallikreins was significantly lower (by at least 70%) than that from native kininogens. This quenching effect on kinin release could primarily be assigned to the modification of the critical Met-361 residue adjacent to the internal kinin sequence in kininogen. However, virtually no kinin could be formed by human plasma kallikrein from NCS-modified HK. This observation suggests involvement of other structural effects detrimental for kinin production. Indeed, NCS-oxidized HK was unable to bind (pre)kallikrein, probably due to the modification of methionine and/or tryptophan residues at the region on the kininogen molecule responsible for the (pro)enzyme binding. Tests on papain inhibition by native and oxidized kininogens indicated that the inhibitory activity of kininogens against cysteine proteinases is essentially insensitive to oxidation.