MG-63 Cells Research Articles

OPTIMIZED SOLID LIPID NANOPARTICLES FOR ENHANCED ORAL BIOAVAILABILITY AND OSTEOGENIC EFFECT OF IPRIFLAVONE: FORMULATION, CHARACTERIZATION, AND IN VITRO EVALUATION

Objective: This study aimed to enhance the oral bioavailability of Ipriflavone (IP) and evaluate its osteogenic effect on human osteosarcoma cells (MG-63) by developing Ipriflavone-loaded Solid Lipid Nanoparticles (IP-SLN). Methods: IP-SLNs were prepared using a modified solvent evaporation method with probe sonication. Formulation optimization employed Central Composite Design (CCD) with independent variables, including lipid amount, surfactant concentration, and sonication time. Characterization was performed using Transmission Electron Microscopy (TEM). In vitro drug release and ex vivo permeation studies were conducted to assess drug release kinetics and bioavailability. Cytotoxicity, Alkaline Phosphatase (ALP) activity, and calcium deposition studies on MG-63 cells evaluated osteogenic effects. Results: TEM images showed round particles with an average diameter of 43.24±3 nm, a zeta potential of-9.53 mV, and a drug entrapment efficiency of 76.53±1.84%. In vitro drug release from IP-SLN was 79.02% compared to 14.21% from IP after 48 h, following the Korsmeyer-Peppas model and first-order kinetics. Ex vivo permeation of IP-SLN was approximately 2-fold higher than IP dispersion. Cytotoxicity studies revealed no toxicity on MG-63 cells. ALP activity and calcium deposition studies indicated that IP-SLN stimulated osteoblast differentiation, increasing alkaline phosphatase activity and mineralization. Pharmacokinetic studies demonstrated that IP-SLN increased the relative bioavailability by 515% compared to ipriflavone. Conclusion: IP-SLN formulations significantly improved the oral bioavailability and osteogenic effects of ipriflavone on MG-63 cells, suggesting potential for novel therapeutic applications in osteoporosis treatment.

Extracellular matrix mimetic supramolecular hydrogels reinforced with covalent crosslinked mesoporous silica nanoparticles.

The extracellular matrix (ECM) is a dynamic environment that is primarily built up from fibrous proteins (e.g., elastins, fibronectins, collagens, and laminins) and plays a vital role in tissue regeneration processes. Therefore, the development of supramolecular hydrogels that can mimic the ECM's dynamicity and fibrous structure is of great interest in regenerative medicine. However, such hydrogels generally have weak mechanical properties and poor structural stability, which significantly limits their potential applications. To overcome this drawback, we developed a new type of hybrid network composed of supramolecular assemblies with covalent nanoparticle-based crosslinkers. The ECM mimetic hydrogels were created through UV-initiated thiol-ene crosslinking between norbornene functionalized benzene-1,3,5-tri carboxamide (NBTA) macromonomers and thiol functionalized mesoporous silica nanoparticles (MSN). We hypothesized that the MSN would improve the mechanical properties by crosslinking the NBTA supramolecular fibrous hydrogels. Notably, the covalent incorporation of MSNs did not disrupt the fibrous morphology of the resulting NBTA-MSN nanocomposites. Furthermore, these supramolecular nanocomposites demonstrated higher structural stability and elasticity compared to pristine NBTA hydrogels. Rheology studies showed that the mechanical properties of NBTA-MSN hydrogels could be tuned by adjusting MSN wt%. Interestingly, NBTA-MSN nanocomposites exhibited self-healing and injectability despite the covalent crosslinking of MSNs. In vitro studies confirmed that NBTA-MSN nanocomposites showed good cytocompatibility and maintained the viability of encapsulated MG63 cells. As a proof of concept, we also demonstrated that MSNs could act as ion reservoirs for calcium and phosphate within the hydrogel networks in addition to being covalent crosslinkers. Taken together, our work offers a promising strategy to create hybrid, biomimetic supramolecular nanocomposite materials for various applications such as injectable materials for bone tissue engineering, and reinforced bioinks for 3D printing applications.

The effect of cold atmospheric plasma on viability of osteoblasts and expression of RANKL and OPG genes in medium with bisphosphonates.

Medication-related osteonecrosis of the jaw is a rare but severe complication with challenging treatment protocols. Cold atmospheric plasma (CAP) has shown promising effects in wound healing, cell proliferation and viability. This study investigated the effect of CAP on osteoblasts in a culture medium containing bisphosphonates. Pilot study was designed to determine the optimal setting of CAP. MG-63 cells were exposed to zoledronic acid at a concentration of 10 micromolar for 72h. Study groups with the best MTT assay results, were chosen for assessing OPG and RANKL genes by RT-PCR. Cell viability was significantly higher in groups 9kV.1mm.90s, 10kV.1mm.60s, and 12kV.1mm.60s (P < 0.05). Expression of RANKL in these groups was significantly lower than the positive control group (medium culture without zoledronic and plasma treatment) and higher than the BP group (culture with zoledronic without plasma treatment), except for the 12kV.1mm.60s group, which did not differ significantly from the positive control group (P > 0.05). OPG decreased in all test groups compared to BP (p < 0.05), except for the 12kV.1mm.60s group, which did not significantly differ from BP (P > 0.05). RANKL/OPG ratio in groups 9kV.1mm.90s and 12kV.1mm.60s significantly increased compared to BP (P < 0.05).CAP treatment may enhance the viability of osteoblasts exposed to bisphosphonates, increase their activity levels, enhance osteoclast activity, and improve bone turnover rates.

Fabrication of hierarchically porous trabecular bone replicas via 3D printing with high internal phase emulsions (HIPEs)

Combining emulsion templating with additive manufacturing enables the production of inherently porous scaffolds with multiscale porosity. This approach incorporates interconnected porous materials, providing a structure that supports cell ingrowth. However, 3D printing hierarchical porous structures that combine semi-micropores and micropores remains a challenging task. Previous studies have demonstrated that using a carefully adjusted combination of light absorbers and photoinitiators in the resin can produce open surface porosity, sponge-like internal structures, and a printing resolution of about 150µm. In this study, we explored how varying concentrations of tartrazine (0, 0.02, 0.04, and 0.08 wt%) as a light absorber affect the porous structure of acrylate-based polymerized medium internal phase emulsions fabricated via vat photopolymerization. Given the importance of a porous and interconnected structure for tissue engineering and regenerative medicine, we tested cell behavior on these 3D-printed disk samples using MG-63 cells, examining metabolic activity, adhesion, and morphology. The 0.08 wt% tartrazine-containing 3D-printed sample (008 T) demonstrated the best cell proliferation and adhesion. To show that this high internal phase emulsion (HIPE) resin can be used to create complex structures for biomedical applications, we 3D-printed trabecular bone structures based on microCT imaging. These structures were further evaluated for cell behavior and migration, followed by microCT analysis after 60 days of cell culture. This research demonstrates that HIPEs can be used as a resin to print trabecular bone mimics using additive manufacturing, which could be further developed for lab-on-a-chip models of healthy and diseased bone.

Medium-entropy Zr–Nb–Ti alloys with low magnetic susceptibility, high yield strength, and low elastic modulus through spinodal decomposition for bone-implant applications

Medium-entropy Zr–Nb–Ti (ZNT) alloys are being extensively investigated as load-bearing implant materials because of their exceptional biocompatibility and corrosion resistance, and low magnetic susceptibility. Nevertheless, enhancing their yield strength while simultaneously decreasing their elastic modulus presents a formidable obstacle, significantly constraining their broader utilization as metallic biomaterials. In this study, three medium-entropy ZNT alloys, i.e., Zr45Nb45Ti10, Zr42.5Nb42.5Ti15, and Zr40Nb40Ti20 (denoted ZNT10, ZNT15, and ZNT20, respectively), were designed based on the miscibility gap in the ZNT phase diagram and prepared by annealing of cold-rolled ingots. Their microstructures, mechanical properties, wear resistance, corrosion resistance, magnetic susceptibility, and biocompatibility were systematically studied. Spinodal decomposition occurred in the cold-rolled ZNT10 and ZNTi15 after annealing at 650°C for 2 h and resulted in nanoscale Zr-rich β1 and (Nb, Ti)-rich β2 phases, which significantly improved their yield strength and reduced their elastic modulus. The wear resistance of the alloys decreased with an increase in Ti content. Dense ZrO2, Nb2O5, and TiO2 oxide layers were formed during the polarization process in Hanks’ solution, which enhanced the corrosion resistance of the alloys. These ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of more than 94 % toward MG-63 cells after culturing for 3 d. Overall, the spinodal ZNT15 showed the best combination of mechanical properties, wear resistance, corrosion resistance, low magnetic susceptibility, and sufficient biocompatibility among the three alloys. Statement of SignificanceThis work reports on medium-entropy Zr–Nb–Ti (ZNT) alloys with heterostructure. Spinodal decomposition significantly improved their mechanical strength and reduced the elastic modulus of the alloys. The wear resistance of the ZNT alloys decreased with an increase in Ti content. Dense ZrO2, Nb2O5, and TiO2 oxide layers were formed during the polarization process in Hanks’ solution, which enhanced the corrosion resistance of the alloys. The ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of more than 94% toward MG-63 cells after culturing for 3 d. The results demonstrate that spinodal ZNT alloys have enormous potential as bone-implant materials due to their outstanding overall mechanical properties, high corrosion resistance, wear resistance, low magnetic susceptibility, and sufficient biocompatibility.

Electrophoretic deposition of curcumin-loaded mesoporous bioactive glass nanoparticle-chitosan composite coatings on titanium for treating tumor-induced bone defect

Clinical treatment of osteosarcoma (OS) presents significant challenges in postoperative tumor recurrence and large segmental bone defects, often necessitating joint replacement or artificial bone implantation to repair failed or defective bone tissue. At the same time, fibroblastic encapsulation can impede direct contact between implants and bones, leading to implant failure. To tackle these issues, mesoporous bioactive glass nanoparticles (MBN) were synthesized and then loaded with curcumin (CUR). Subsequently, chitosan (CTS) was chosen as the charger and coating matrix, and electrophoretic deposition (EPD) was utilized to fabricate a CTS-MBN-CUR composite coating with triple functionality on Ti implants aiming for OS-induced bone repair. MBN-CUR nanoparticles are encapsulated in CTS and uniformly distributed within the coating, achieving robust adhesion and long-term release of CUR. Concurrently, the developed CTS-MBN-CUR coating exhibits moderate hydrophilicity, and good bioactivity. Moreover, three different types of cells, MC3T3-E1, L929, and MG63 cells, were individually cultured with the composite coating and subjected to comprehensive cellular studies. The coating presented favorable bioactivities, and osteogenic performance, and the ability to resist the activity of fibroblast and OS cells. These findings suggest that CTS-MBN-CUR holds promising potential for bone regeneration following OS resection surgery.

A Novel Cortex Phellodendri Chinensis-Based Carbon Dots Platform for Remarkable Analgesia for Clinical Pain Management.

In this study, we explored the eco-friendly synthesis of photoluminescent CCDs employing a direct one-step pyrolysis process, utilizing natural Cortex Phellodendri Chinensis as the precursor material and studied their analgesic effect in mice. The synthesized carbon dots underwent comprehensive characterization through a range of spectroscopic and microscopic techniques. These included UV-Vis, FTIR, fluorescence spectroscopy and HR-TEM, DLS instruments. HR-TEM results exhibited the presence of homogenous spherical-shaped C-dots of about 3.3nm without aggregates. Furthermore, the prepared CCDs were studied for their in vivo analgesic effect in mice by performing tail-immersion, hot plate and acetic acid writhing tests. Also, an MTT assay was performed to assess the in vitro cytotoxicity of CCDs against L929 cells. In vitro cytotoxicity studies revealed that L929 cells exhibited higher cell viability when treated with prepared CCDs. The cellular uptake studies revealed the phase contrast images of MG-63 cells at wavelength 488nm clearly depicted the aggregation of green, fluorescent CCDs within the cells while leaving nuclei unobscured. In addition, to the best of our understanding, the results presented in this paper showed that CCDs exhibited an important analgesic effect and enhanced anti-nociceptive activity, which may be due to stimulation of the opioidergic system. Consequently, CCDs appear to be a viable analgesic alternative for traditional analgesic candidates in pain management.

FRESH 3D printing of zoledronic acid-loaded chitosan/alginate/hydroxyapatite composite thermosensitive hydrogel for promoting bone regeneration

The aim of this study was to develop a composite thermosensitive hydrogel for bone regeneration applications. This hydrogel consisted of chitosan, alginate and hydroxyapatite, and was loaded with zoledronic acid as a model drug. The feasibility of three-dimensional (3D) printing of the thermosensitive hydrogel using the extrusion technique was investigated. The 3D printing technique called Freeform Reversible Embedded Suspended Hydrogel (FRESH) printing was employed for this purpose. To characterize the composite hydrogels, several tests were conducted. The gelation time, rheological properties, and in vitro drug release were analyzed. Additionally, the cell viability test on human osteosarcoma MG-63 cells for the composite hydrogel was assessed using an MTT assay. The results of the study showed that the zoledronic acid-loaded composite thermosensitive hydrogel was successfully printed using the FRESH 3D printing technique which was not possible otherwise i.e., by using traditional 3D printing techniques. Further examination of the printed constructs using a Scanning Electron Microscope revealed the presence of porous and layered structures. The gelation times of the composite thermosensitive hydrogel was determined to be 10 and 20 min, respectively for scaffolds with and without HA, indicating the successful formation of the gel within a reasonable time to the FRESH technique. The flow behavior of the hydrogel was found to be pseudoplastic, following a non-Newtonian flow pattern with Farrow’s constant (N) values of 1.708 and 1.853 for scaffolds with and without hydroxyapatite, respectively. In terms of drug release, scaffolds prepared with and without hydroxyapatite reached nearly 100% of zoledronic acid release in 360 h and 48 h, respectively. The cell viability test on human osteosarcoma MG-63 cells using MTT assay has shown increased cell viability % in the case of the composite hydrogel, indicating a biocompatible scaffold. Overall, this study successfully developed a composite thermosensitive hydrogel loaded with zoledronic acid for bone regeneration applications and 3D printed using the FRESH 3D printing technique. The results of this study provide valuable insights into the potential use of this composite hydrogel for future biomedical applications.

Development and characterization of PLA nanocomposites reinforced with bio-ceramic particles for orthognathic implants: Enhanced mechanical and biological properties

The clinical application of osteofixation materials is crucial for maxillofacial reconstruction and orthognathic surgeries. To overcome the limitations of traditional metallic implants, bioabsorbable materials are gaining popularity due to their ability to avoid secondary removal surgeries and reduce stress shielding. This study investigates third-generation biomaterials, focusing on polylactic acid (PLA) for its biocompatibility and biodegradability, and hydroxyapatite (HAP) for its bioactive osteoconductive and bioresorbable properties. Eggshell nanoparticles (ES-NP), HAP, and bioinert alumina particles coated with titanium dioxide (TiO2@Al2O3) were prepared using ball milling, co-precipitation, and sol-gel methods, respectively. PLA-based nanocomposites PLA/ESNP/Al2O3 (PEA), PLA/HAP/Al2O3 (PHA), PLA/ESNP/TiO2@Al2O3 (PEAT), and PLA/HAP/TiO2@Al2O3 (PHAT) were fabricated via solvent casting. Characterization techniques including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), and Field-Emission Scanning Electron Microscopy (FE-SEM) were used to analyze the developed nanoparticles and composites. Results indicated PEAT and PHAT composites exhibited tensile strengths of 33.59 ± 0.38 MPa and 32.46 ± 0.46 MPa, tensile moduli of 1756.17 ± 95.43 MPa and 2367.21 ± 158.84 MPa, and shore d hardness values of 84.10 ± 1.45 SHN and 78.00 ± 2.25 SHN, respectively. Both composites achieved a wettability angle of ∼65° and surface roughness below 2.19 μm, enhancing osteoblast adhesion. Additionally, MG63 cell viability was approximately 80 %, and hemolysis rates were below 2.17 %, demonstrating their potential for maxillofacial implant applications.

A silver lining in MRSA treatment: The synergistic action of poloxamer-stabilized silver nanoparticles and methicillin against antimicrobial resistance

BackgroundIncreasing antibiotic resistance in bacterial infections, including drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates innovative therapeutic solutions. Silver nanoparticles are promising for combating infections, but toxicity concerns emphasize the importance of factors like dosage, size, shape, and surface chemistry. Hence, exploring poloxamer as a stabilizing agent to reduce its toxicity and enhance the antibacterial effect on MRSA is investigated. MethodsSilver nanoparticles stabilized with poloxamer (AgNPs@Pol) were synthesized through the chemical reduction method and characterized using UV–visible spectrophotometer, HR-TEM, DLS, and Zeta potential measurements. Subsequently, the antibacterial activity of AgNPs@Pol alone and in combination with methicillin against MRSA and methicillin-susceptible S. aureus (MSSA) was evaluated using the broth microdilution method. ResultsAgNPs@Pol showed significant efficacy against MRSA and MSSA, achieving a 100 % reduction in colony-forming units (CFU) at 9.7 μg/ml. The minimum inhibitory concentration (MIC) against MRSA and MSSA was 8.6 μg/ml and 4.3 μg/ml, respectively. A synergistic effect was observed when AgNPs@Pol was combined with methicillin. Treatment with AgNPs@Pol increased reactive oxygen species (ROS) production in both strains, contributing to its antibacterial activity. Real-time qPCR analysis indicated the downregulation of genes involved in antimicrobial resistance and cell adhesion in both strains. Further, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated low cytotoxicity for AgNPs@Pol against MCF-7, MG-63, and NIH-3T3 cell lines. ConclusionThe developed AgNPs@Pol demonstrated extensive colloidal stability, potent antibacterial activity and synergistic effect with methicillin against MRSA and MSSA. Further studies in primary cells and in vivo models may validate its potential for clinical applications.

Fabrication and characterization of new hot extruded ZK60/CNTs+AgNPs nanocomposites for biomedical applications

Magnesium (Mg), with properties such as biodegradability and having a density and elasticity coefficient close to the bones of the body, has attracted a lot of attention as a serious option for orthopedic applications. However, the low compressive strength of Mg compared to the human bone and its weak antibacterial function limit its applications as a substitute for temporary implants to be used under load-bearing conditions. The aim of this paper is to evaluate the synergistic effect of CNTs + AgNPs nanofillers on the in vitro degradation, mechanical and antibacterial behavior of new ZK60/xCNTs + xAgNPs(x: 0, 0.25, 0.5, 1) composites made using semi powder metallurgy, followed by hot extrusion method. The ZK60/0.5CNTs+0.5 AgNPs (CA2) composite boasts a higher ultimate compressive strength (UCS) of 371 ± 15 MPa compared to 297 ± 6 MPa for ZK60 based alloys. The CA2 composite also exhibits a grain size of 9.8 μm and a microhardness of 81 HV.Also, the antibacterial activity assessment demonstrated that adding CNTs + AgNPs hybrid nanofillers to the Mg matrix could notably prevent growing and penetration of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which indicates the synergy between antibacterial mechanisms of CNTs and AgNPs. Cytotoxicity studies confirm that composites with low amounts of CNTs + AgNPs did not show cytotoxic behavior against MG63 cells, although higher loading of CNTs + AgNPs caused toxicity. Also, the examination of osteogenic activity is consistent with other results. In general, according to the results, the potential application of CA2 composite for under load bearing implant application and bone infection treatment is proved.

Protein Nano Coop Complexes Promote Fracture Healing and Bone Regeneration in a Zebrafish Osteoporosis Model.

Nanotherapeutic techniques are becoming increasingly important in the treatment of bone disorders owing to their targeted drug delivery. This study formulates zein nano coop composites containing chimeric antioxidants (ascorbic acid, luteolin, resveratrol, and coenzyme Q) (AZN) and evaluates its application in bone regeneration using osteoblasts and a Zebrafish osteoporosis model. In vitro experiments with human osteoblast-like MG63 cells showed enhancement of bone mineralization and regeneration. It further exhibited high biocompatibility in Zebrafish larvae, with increased calcium/phosphorus deposition and upregulation of osteogenic genes. The study has unequivocally demonstrated the potential of AZN in bone regeneration and fracture healing in both normal and osteoporosis models, underscoring the significance of this research. Further investigations using higher animal models are warranted to expand on these findings. The impact of this research seems far-reaching, with the possible development of new, effective, and safe treatment options for osteoporosis, addressing the limitations of the currently available treatments.

Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy

BackgroundOsteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6. MethodsFirstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot. ResultsHKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6. ConclusionsHKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.

Functionalized polyaniline nanofibrils on lamellar structured zirconium for effective bone mineralization

The surface physiology of certain implant material has the ability to promote implant–cell signalling process through which a stable environment is formed. The formation of this favourable environment hastens the process of biomineralization and regeneration. In this context, Zirconium (Zr) when treated with alkali undergoes a surface modification which results in the development of a lamellar structured Zirconium (ATZ). Further, encapsulation of polyaniline (PAni) on ATZ was achieved through the electropolymerization technique which results in an effective and homogeneous electrodeposition of PAni nanofibrils on ATZ surface. A high resolution scanning electron microscope analysis (HR-SEM), phase analysis and functional group analysis were carried out confirming the semi-crystalline PAni nanofibrils braided on the ATZ surface. Potentiodynamic polarization studies of the coated sample exhibited higher Ecorr (−0.060 V) and lower icorr (0.007 µA/cm2) values signifying its better corrosion resistance behaviour in higher potentials coupled with lower electrochemical activity in the SBF medium. The porosity of PAni/ATZ nanofibril was 0.007 % and it provides an effective platform for implant-tissue attachment. The In-vitro biomineralization studies proved the bioactivity of PAni/ATZ which forms well-matured HAp spherules over the surface. Further, hemocompatibility studies of PAni/ATZ expressed a hemolytic rate of ∼0.39 % which denotes it’s biocompatible and non-hemolytic behaviour with the blood cells. Further, the coated sample on gram-positive and gram-negative bacteria causes demise of bacterial cell wall and exhibits higher inhibition percentage. In addition, a standard MTT assay of PAni/ATZ provides an effective support in maintaining cell viability and aids in proliferation of MG-63 cells. Thus, the results demonstrate that the nanoscale surface architecture of PAni/ATZ could serve as a potential and conducive environment for bone-implant interaction on the implant material for better osseointegration.

Novel platinum nanoclusters (Pt NCs) induce mitochondrial apoptosis and damaging autophagy for the treatment of osteosarcoma—from the perspective of P53 mutation status in different cell lines

This study aimed to investigate the anticancer efficacy and underlying mechanism of novel platinum nanoclusters (Pt NCs) in osteosarcoma cell lines exhibiting distinct P53 expression profiles, namely MG-63 (P53−) and U2-OS (P53+). The findings revealed that Pt NCs exerted an inhibitory effect on proliferation, migration, and colony formation while promoting apoptosis in both MG-63 (P53−) and U2-OS (P53+) cells. The inhibitory effect on the malignant characteristics of MG-63 (P53−) cells was more obvious, indicating that the potential anticancer effect of Pt NCs was not dependent on P53. Animal experiments have substantiated the in vivo anticancer properties of Pt NCs, while also revealing their lower toxicity on cells and tissues. Pt NCs possess the ability to impede cell proliferation by inducing DNA damage and arresting the cell cycle in the G1 phase and possess the ability to promote BAX/Bcl-2/Caspase-3/mitochondrial apoptosis. Pt NCs may promote mitochondrial apoptosis by promoting damaging autophagy, thereby promoting cellular demise. This study has confirmed the P53-independent anticancer impact of Pt NCs on osteosarcoma in vitro and in vivo. Pt NCs may play a therapeutic role in more sensitive MG-63 (P53−) cells by promoting DNA damage to arrest the cell cycle, stimulating BAX/Bcl-2/Caspase-3/mitochondrial apoptosis, and initiating damaging autophagy.

Aucubin Induces Apoptotic Cell Death Through Caspase-dependent Pathways in Human Osteosarcoma MG-63 Cells

Background Osteosarcomas (OSs) are predominantly generated by mesenchymal cells, which commonly develop in the distal and upper regions of the bones. OS has high mortality rates and treatment failures, mostly due to the presence of lung metastases. Purpose The present work aimed to scrutinize the anticancer potentials of aucubin against OS human osteosarcoma (MG-63) cells. Methods The proliferation of the control and aucubin-treated MG-63 cells was studied by an XTT assay. Various fluorescent staining assays were done to assess the endogenous reactive oxygen species (ROS) accumulation and apoptosis in the aucubin-treated MG-63 cells. The caspase-3, -8, and -9 activities were investigated using the assay kits. Results The XTT assay results confirmed that the aucubin treatment considerably reduced the MG-63 cells. The findings of the various fluorescent staining assays evidenced that the aucubin treatment remarkably promoted endogenous ROS accumulation and apoptosis in the OS cells. The caspase activities were also improved in the OS cells after the aucubin treatment. Conclusion The results of this work show that aucubin treatments inhibit cell proliferation and trigger apoptosis in MG-63 cells, suggesting its potential as a promising anticancer agent. These findings will facilitate the future development of aucubin as a talented anticancer agent to treat OS.

Optimizing the Pore Structure and Geometry of Polycaprolactone/Graphene Scaffold to Promote Osteogenesis

Introduction: Pore structure and geometry are crucial in scaffold development for tissue engineering. From this viewpoint, pore geometry characterization methods will aid in understanding the influence of pore structure (pore size and diffusivity) on its properties. These properties determine how oxygen and water enter the scaffold, forming adsorption states. Previous studies showed that the addition of graphene (G) to polycaprolactone (PCL) increased the pore size, and played a significant role in tissue regeneration. Therefore, this study aimed to evaluate pore structure, geometry, and viability that are suitable for osteogenesis. Materials and methods: Morphology, size, and size distribution of PCL and PCL/G scaffolds were measured at concentrations of 1, 2, and 3 wt% G for the pore structure, while the connectivity of the scaffold's pore was analyzed using the geodesic tortuosity. This is essential because these factors promote the viability of osteogenesis-supporting cells. Results and discussion: The results showed that 3 wt% G had a good water diffusivity rate, larger pores, better connectivity, and viability than other concentrations. Conclusion: In conclusion, the presence of G in scaffolds affects the pore geometry and structure. This results in several advantageous effects that support osteogenesis, such as increased water and nutrient uptake, enhanced waste metabolism transport, and increased viability of the cells. HIGHLIGHTS Pore structure and geometry are essential for tissue engineering scaffold development. 3 wt% G concentration exhibited better interconnectivity compared to PCL. Larger pore sizes improve fluid flow because of the higher diffusivity of the scaffold. MG-63 cells, resembling osteoblasts, exhibited enhanced proliferation at 3 wt% G. GRAPHICAL ABSTRACT

Fabrication of copper ion-substituted hydroxyapatite/Silk fiber/Methylcellulose composite: mechanical, antimicrobial, hemocompatibility, bioactivity and cytocompatibility evaluation

Herein, we reported the preparation of copper substituted hydroxyapatite (Cu-HAP) and fabrication of electrospun composites using Cu-HAP, SF (Silk fiber) and MC (Methylcellulose) by E-Spin method. Characterization techniques such as XRD (phase formation), FTIR (chemical bonds), SEM and EDAX (surface morphology and elemental composition) were carried out. Porosity measurement, swelling and mechanical properties were carried out to investigate the physicochemical properties of the fabricated electrospun composites. The hemocompatibility analysis indicated a hemolysis ratio < 2 %, which confirms the blood compatibility nature of the composite. Antibacterial activity of Copper hydroxyapatite/silk fiber/ Methylcellulose electrospun composite showed estimable activity against E.coli (zone of inhibition: 46 ± 0.94 mm) compared with pure SF/MC electrospun composite (33 ± 1.21). Bioactivity study confirmed the development of bone-like apatite on the surfaces of optimized (SF/MC 30 wt% of Cu-HAP) electrospun composite. Furthermore, MG63 cells were utilised to study the biocompatibility of the enhanced electrospun composite and good cell viability (99.93 ± 0.12 % using 25 μg/mL) was observed from microscopic image and the results showed that 30 wt% of Cu-HAP added polymer composite has outstanding osteoinductivity, biocompatibility, and antibacterial results, making it a very valuable aspirant for use in bone tissue engineering (BTE) applications to repair bone defects.

Multifunctional zinc oxide loaded stearic acid surfaces on biodegradable magnesium WE43 alloy with hydrophobic, self-cleaning and biocompatible attributes

Biodegradable Mg alloys are one of the most promising materials for implant applications, for which the widespread use is hampered by rapid degradation in physiological environment. The present study explores the development of a novel zinc-oxide (ZnO) loaded stearic acid (SA) coating on medical grade WE43 alloy using a facile, and environment-friendly technique for promising biomaterial surface applications. Morphology and chemical analyses reveal the development of a layered coating surface with uniformly dispersed ZnO nanoparticles in SA matrix. The developed coating exhibits hydrophobic performance (contact angle of 135°) along with the retainment of hydrophobicity under varying chemical (acidic pH of 1 and basic pH of 13) and mechanical (post scratch testing and peel-off studies) conditions. The observed surface water repellency facilitates self-cleaning performance pointing towards its efficacy against potential biofilm formation. The developed coating demonstrates superior resistance against surface degradation during immersion studies in phosphate buffer saline solution (pH = 7.4) and better cell viability with MG-63 (human osteosarcoma) cell line. The approach presented here sets a platform for the development of efficient coatings on biodegradable WE43 alloys surfaces for potential biomaterial technologies.

Biodiversity and Bioprospecting of Fungal Endophytes from Houttuynia cordata Thunb. as a Potential Antibacterial and Anticancer Agent.

Endophytic fungi are considered a new source of bioactive compounds that have important applications in agriculture and medicine. This study aims to investigate the biodiversity and potential of endophytic fungi isolated from Houttuynia cordata Thunb. as antimicrobials and anticancer agents. Out of ten isolated endophytes, four species have never been reported to be associated with H. cordata: Ceratobasidium sp., Cladosporium sp., Phomopsis sp., and Fusarium sp. The antibacterial activity assay revealed that the ethyl acetate extract of Ceratobasidium sp. HCS-3 possessed most potent antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, its cytotoxic activity test showed the promising anticancer activity on lung cancer A549, osteosarcoma MG-63, and cervical cancer HeLa cells with IC50 of 4.55 ±1.16, 32.14 ±2.78, and 1.54 ±0.66 ppm, respectively. Furthermore, metabolite profiling identified 66 compounds suggesting that benzoic acid, farnesol, and cyclopeptides may contribute to the antibacterial activity, while 4-methoxycinnamic acid may have anticancer potential.