Search Results (11)

Beta (β)-type Ti-29Nb-13Ta-4.6Zr (TNTZ) alloys combine low modulus with biocompatibility but require improved surface properties for long-term implantation. This study aimed to enhance the surface mechanical strength and antibacterial performance of TNTZ by applying TiN and TiAlN coatings via PVD. Notably, TiAlN was deposited on TNTZ for the first time, enabling a direct side-by-side comparison with TiN under identical deposition conditions. Dense TiN (~1.06 μm) and TiAlN (~1.73 μm) coatings were deposited onto solution-treated TNTZ and characterized by X-ray diffraction, scanning probe microscopy, Vickers microhardness, Rockwell indentation test (VDI 3198), static water contact angle measurements, and a Kirby–Bauer disk-diffusion antibacterial assay against Escherichia coli (E. coli). Both coatings formed face-centered cubic (FCC) structures with smooth interfaces (Ra ≤ 5.3 nm) while preserving the single-phase β matrix of the substrate. The hardness increased from 192 HV (uncoated) to 1059 HV (TiN) and 1468 HV (TiAlN), and the adhesion quality was rated as HF2 and HF1, respectively. The surface wettability changed from hydrophilic (48°) to moderately hydrophobic (82°) with TiN and highly hydrophobic (103°) with TiAlN. Similarly, the diameter of the no-growth zones increased to 18.02 mm (TiN) and 19.09 mm (TiAlN) compared to 17.65 mm for uncoated TNTZ. The findings indicate that TiAlN, in particular, provided improved hardness, adhesion, and hydrophobicity. Preliminary bacteriostatic screening under diffusion conditions suggested a modest relative antibacterial response, though the effect was not statistically significant between coated and uncoated TNTZ. Statistical analysis confirmed no significant difference between the groups (p > 0.05), indicating that only a preliminary bacteriostatic trend— rather than a definitive antibacterial effect—was observed. Both nitride coatings strengthened TNTZ without compromising its structural integrity, making TiAlN-coated TNTZ a promising candidate for next-generation orthopedic implants. Full article

Sclerostin is a bone formation inhibitor produced by osteocytes. Although sclerostin is mainly expressed in osteocytes, it was also reported in periodontal ligament (PDL) fibroblasts, which are cells that play a role in both osteogenesis and osteoclastogenesis. Here, we assess the role of sclerostin and its clinically used inhibitor, romosozumab, in both processes. For osteogenesis assays, human PDL fibroblasts were cultured under control or mineralizing conditions with increasing concentrations of sclerostin or romosozumab. For analyzing osteogenic capacity and alkaline phosphatase (ALP) activity, alizarin red staining for mineral deposition and qPCR of osteogenic markers were performed. Osteoclast formation was investigated in the presence of sclerostin or romosozumab and, in PDLs, in the presence of fibroblasts co-cultured with peripheral blood mononuclear cells (PBMCs). PDL-PBMC co-cultures stimulated with sclerostin did not affect osteoclast formation. In contrast, the addition of romosozumab slightly reduced the osteoclast formation in PDL-PBMC co-cultures at high concentrations. Neither sclerostin nor romosozumab affected the osteogenic capacity of PDL fibroblasts. qPCR analysis showed that the mineralization medium upregulated the relative expression of osteogenic markers, but this expression was barely affected when romosozumab was added to the cultures. In order to account for the limited effects of sclerostin or romosozumab, we finally compared the expression of SOST and its receptors LRP-4, -5, and -6 to the expression in osteocyte rich-bone. The expression of SOST, LRP-4, and LRP-5 was higher in osteocytes compared to in PDL cells. The limited interaction of sclerostin or romosozumab with PDL fibroblasts may relate to the primary biological function of the periodontal ligament: to primarily resist bone formation and bone degradation to the benefit of an intact ligament that is indented by every chew movement. Full article

The major cause (more than 90%) of all cancer-related deaths is metastasis, thus its prediction can critically affect the survival rate. Metastases are currently predicted by lymph-node status, tumor size, histopathology and genetic testing; however, all these are not infallible, and obtaining results may require weeks. The identification of new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies. Recently, the new mechanobiology-related techniques, independent of genetics, based on the mechanical invasiveness of cancer cells (microfluidic, gel indentation assays, migration assays etc.), demonstrated a high success rate for the detection of tumor cell metastasis propensity. However, they are still far away from clinical implementation due to complexity. Hence, the exploration of novel markers related to the mechanobiological properties of tumor cells may have a direct impact on the prognosis of metastasis. Our concise review deepens our knowledge of the factors that regulate cancer cell mechanotype and invasion, and incites further studies to develop therapeutics that target multiple mechanisms of invasion for improved clinical benefit. It may open a new clinical dimension that will improve cancer prognosis and increase the effectiveness of tumor therapies. Full article

Optical tweezers have been a fixture of microscopic cell manipulation since the 1990s. Arthur Ashkin’s seminal work has led to the advancement of optical tweezers as an effective tool for assay development in the fields of physics and nanotechnology. As an advanced application of cell manipulation, optical tweezers have facilitated the study of a multitude of cellular and molecular interactions within the greater field of nanotechnology. In the three decades since the optical tweezers’ rise to prominence, different and versatile assays have emerged that further explore the biochemical pathways integral for cell proliferation and communication. The most critical organelle implicated in the communication and protection of single cells includes the plasma membrane. In the past three decades, novel assays have emerged which examine the plasma membrane’s role in cell-to-cell interaction and the specific protein components that serve integral membrane functions for the cell as a whole. To further understand the extent to which optical tweezers have evolved as a critical tool for cellular membrane assessment within the field of nanotechnology, the various novel assays, including pulling, indentation, and stretching assays, will be reviewed in the current research sector. Full article

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA. Full article

MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and instead become resistant to UV-induced senescence. The irregular nuclear shape is also observed in isolated cells and in those without TJs, due to the lack of extracellular calcium. The aberrant nuclear shape of ZO-2 KD cells is not accompanied by a reduced expression of lamins A/C and B and lamin B receptors. Instead, it involves a decrease in constitutive and facultative heterochromatin, and microtubule instability that is restored with docetaxel. ZO-2 KD cells over-express SUN-1 that crosses the inner nuclear membrane and connects the nucleoskeleton of lamin A to nesprins, which traverse the outer nuclear membrane. Nesprins-3 and -4 that indirectly bind on their cytoplasmic face to vimentin and microtubules, respectively, are also over-expressed in ZO-2 KD cells, whereas vimentin is depleted. SUN-1 and lamin B1 co-immunoprecipitate with ZO-2, and SUN-1 associates to ZO-2 in a pull-down assay. Our results suggest that ZO-2 forms a complex with SUN-1 and lamin B1 at the inner nuclear membrane, and that ZO-2 and cell–cell contacts are required for a normal nuclear shape. Full article

In this study, the innovative dip-coating technique treated titanium (IDCT-Ti) implant with tetrapeptide Gly-Arg-Gly-Asp (GRGD) coating was investigated for its potential to enhance osseointegration. The L929 fibroblast cells were cultured in different concentrations of the GRGD (1%, 2%, and 5%). The cell viability was assessed through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead staining. The surface topography and nano-indentation were analyzed by atomic force microscopy. The hemocompatibility was evaluated via field-emission scanning electron microscopy, while contact angle analysis was detected by a goniometer. Radiograph evaluation was determined by panoramic imaging. It was found that the cell growth increased and had a survival rate of more than 70% in 1% GRGD. The mortality of L929 increased with the higher concentration of GRGD. The IDCT-Ti coated with 1% GRGD showed a nano-surface with a Young’s modulus that was similar to human cortical bone, and it displayed greater red blood cell accumulations with abundant fibrin formation. As regards the wettability, the IDCT-Ti coated with 1% GRGD was lower than the SLA (sandblasted, large-grit, and acid-etched) treated implant. The X-ray image exhibited no bone loss around the implant at six months after placement. As a result, this study suggests that the IDCT-Ti implant, coated with 1% GRGD, has a tremendous likeliness to enhance osseointegration. Full article

A novel bioactive glass containing therapeutic ions with enhanced biocompatibility was designed and produced by the classical melt-quenching route. Starting from a very promising composition (Bio_MS), which combined bioactivity and high crystallization temperature, the ratio between some oxides was tailored to obtain a new and more reactive (in terms of dissolution rate) bioactive glass, called BGMSN (composition in mol%: 6.1 Na₂O, 31.3 CaO, 5 MgO, 10 SrO, 2.6 P₂O₅, 45 SiO₂). The aim of this work was to produce a bioactive glass with a good biological performance, preserving, at the same time, the high crystallization temperature achieved for Bio_MS; this is strategic in order to avoid undesired crystalline phases during thermal treatments, which can undermine the bioactivity and even the stability of final products. A complete characterization of the novel bioactive glass was performed in terms of thermal, mechanical and biological properties and in vitro bioactivity. The thermal behavior of the bioactive glass was studied by heating microscopy, differential thermal analysis (DTA) and optical dilatometry; BGMSN showed a very high crystallization temperature and a high sinterability parameter, thus being suitable for applications where thermal treatments are required, such as sintered samples, coatings and scaffolds. Mechanical properties were investigated by the micro-indentation technique. The in vitro biological properties were evaluated by means of both direct and indirect cell tests, i.e., neutral red (NR) uptake and MTT assay, using murine long bone osteocyte Y4 (MLO-Y4) cells: the cellular viability of BGMSN was higher compared to cellular viability of 45S5, both in direct and indirect tests. Finally, the in vitro bioactivity test by soaking samples in simulated body fluid (SBF) showed high dissolution rate, with a good rate of formation of hydroxyapatite. Full article

Concentrated collagen hydrolysate (HC10CC), rabbit collagen glue (RCG), and keratin hydrolysate (KH) were investigated in terms of their extraction from mammalian by-products and processing by electrospinning. The electrospun nanofibers were characterized by scanning electron microscopy coupled with the energy dispersive X-ray spectroscopy (SEM/EDS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and indentation tests. The cytotoxicity of the electrospun nanofibers was conducted on L929 fibroblast cells using MTT and LDH assays and cell morphology observations. The electrospun RCG and KH nanofibers morphology showed an average size of nanofibers ranging between 44 and 410 nm, while the electrospun HC10CC nanofibers exhibited higher sizes. The ATR-FTIR spectra performed both on extracted proteins and electrospun nanofibers showed that the triple helix structure of collagen is partially preserved. The results were in agreement with the circular dichroism analysis for protein extracts. Furthermore, the viscoelastic properties of electrospun KH nanofibers were superior to those of electrospun RCG nanofibers. Based on both in vitro quantitative and qualitative analysis, the electrospun nanofibers were not cytotoxic, inducing a healthy cellular response. The results of new electrospun protein-based nanofibers may be useful for further research on bioactive properties of these nanofibers for tissue engineering. Full article

Zr-based bulk metallic glasses (Zr-BMGs) are potentially the next generation of metallic biomaterials for orthopaedic fixation devices and joint implants owing to their attractive bulk material properties. However, their poor tribological properties and long-term biocompatibility present major concerns for orthopaedic applications. To this end, a novel surface modification technology, based on ceramic conversion treatment (CCT) in an oxidising medium between the glass transition temperature and the crystallisation temperature, has been developed to convert the surface of commercially available Zr₄₄Ti₁₁Cu₁₀Ni₁₁Be₂₅ (Vitreloy 1b) BMG into ceramic layers. The engineered surfaces were fully characterised by in-situ X-ray diffraction, glow-discharge optical emission spectroscopy, scanning electron microscopy, transmission electron microscopy, and scanning transmission electron microscopy. The mechanical, chemical, and tribological properties were evaluated respectively by nano-indentation, electrochemical corrosion testing, tribological testing and the potential biocompatibility assessed by a cell proliferation assay. The results have demonstrated that after CCT at 350 °C for 40 h and at 380 °C for 4.5 h the original surfaces were converted into to a uniform 35–55-nm-thick oxide layer (with significantly reduced Ni and Cu concentration) followed by a 200–400-nm-thick oxygen-diffusion hardened case. The surface nano hardness was increased from 7.75 ± 0.36 to 18.32 ± 0.21 GPa, the coefficient of friction reduced from 0.5–0.6 to 0.1–0.2 and the wear resistance improved by more than 60 times. After 24 h of contact, SAOS-2 human osteoblast-like cells had increased surface coverage from 18% for the untreated surface to 46% and 54% for the 350 °C/40 h and 380 °C/4.5 h treated surfaces, respectively. The significantly improved tribological properties and biocompatibility have shown the potential of the ceramic conversion treated Zr-BMG for orthopaedic applications. Full article

Valvular dysfunction as the prominent reason of heart failure may causes morbidity and mortality around the world. The inability of human body to regenerate the defected heart valves necessitates the development of the artificial prosthesis to be replaced. Besides, the lack of capacity to grow, repair or remodel of an artificial valves and biological difficulty such as infection or inflammation make the development of tissue engineering heart valve (TEHV) concept. This research presented the use of compound of poly-l-lactic acid (PLLA), thermoplastic polyurethane (TPU) and maghemite nanoparticle (γ-Fe₂O₃) as the potential biomaterials to develop three-dimensional (3D) aortic heart valve scaffold. Electrospinning was used for fabricating the 3D scaffold. The steepest ascent followed by the response surface methodology was used to optimize the electrospinning parameters involved in terms of elastic modulus. The structural and porosity properties of fabricated scaffold were characterized using FE-SEM and liquid displacement technique, respectively. The 3D scaffold was then seeded with aortic smooth muscle cells (AOSMCs) and biological behavior in terms of cell attachment and proliferation during 34 days of incubation was characterized using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal laser microscopy. Furthermore, the mechanical properties in terms of elastic modulus and stiffness were investigated after cell seeding through macro-indentation test. The analysis indicated the formation of ultrafine quality of nanofibers with diameter distribution of 178 ± 45 nm and 90.72% porosity. In terms of cell proliferation, the results exhibited desirable proliferation (109.32 ± 3.22% compared to the control) of cells over the 3D scaffold in 34 days of incubation. The elastic modulus and stiffness index after cell seeding were founded to be 22.78 ± 2.12 MPa and 1490.9 ± 12 Nmm², respectively. Overall, the fabricated 3D scaffold exhibits desirable structural, biological and mechanical properties and has the potential to be used in vivo. Full article