Search

The effects of adding Al2O3 nanoparticles on the microstructure, tribological, magnetic, and corrosion properties of CuFe-Al2O3 nanocomposites were investigated in this work. The mixture of Cu-25 wt.% Fe powder with 5 vol.% Al2O3 was mechanically milled. X-ray diffraction results revealed that after 60 h of mechanical alloying, CuFe solid solution was formed. Magnetic hysteresis loops of the mechanically alloyed powders were extracted at room temperature. The morphology and elemental analysis of the sintered specimens were studied by field emission scanning electron microscope (SEM). It was observed that uniform distribution and embedding of Al2O3 nanoparticles in the CuFe alloy matrix in nanocomposites were achieved, which exhibited excellent performances. Tribological properties were evaluated through a pin-on-disk wear test, and it was found that by the addition of Al2O3 nanoparticles to CuFe alloy, the weight loss rate was reduced by 30%. The existence of Al2O3 nanoparticles in the matrix of CuFe alloy causes the wear mechanism change from adhesive to abrasive, which means a considerable wear resistance was obtained in nanocomposites. The corrosion properties of the sintered samples in a solution of 3.5% NaCl were studied by potentiodynamic polarization. With the addition of Al2O3 nanoparticles, the corrosion rate of the alloy was reduced by 75%.

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.

Natural bone constitutes a complex and organized structure of organic and inorganic components with limited ability to regenerate and restore injured tissues, especially in large bone defects. To improve the reconstruction of the damaged bones, tissue engineering has been introduced as a promising alternative approach to the conventional therapeutic methods including surgical interventions using allograft and autograft implants. Bioengineered composite scaffolds consisting of multifunctional biomaterials in combination with the cells and bioactive therapeutic agents have great promise for bone repair and regeneration. Cellulose and its derivatives are renewable and biodegradable natural polymers that have shown promising potential in bone tissue engineering applications. Cellulose-based scaffolds possess numerous advantages attributed to their excellent properties of non-toxicity, biocompatibility, biodegradability, availability through renewable resources, and the low cost of preparation and processing. Furthermore, cellulose and its derivatives have been extensively used for delivering growth factors and antibiotics directly to the site of the impaired bone tissue to promote tissue repair. This review focuses on the various classifications of cellulose-based composite scaffolds utilized in localized bone drug delivery systems and bone regeneration, including cellulose-organic composites, cellulose-inorganic composites, cellulose-organic/inorganic composites. We will also highlight the physicochemical, mechanical, and biological properties of the different cellulose-based scaffolds for bone tissue engineering applications.

Emerging bioengineering approaches such as three-dimensional (3D) cell culture methods have opened new avenues for scaffolds combined with various therapeutic agents in bone tissue regeneration. In this regard, bioceramic nanocomposite compounds have been prominently studied in bone and dental tissue engineering, due to their potential for diseased bone regeneration. We synthesized in situ bioceramic nanocomposite using a combination of sol–gel and mechanical activation that the nanocomposite contained Akermanite as a major phase, and Monticellite as a minor phase. After physicochemical characterization (crystallite size of Ak and Mon were 58 and 48 nm respectively), cell viability and pertinent biological studies of the nanocomposite powder showed 1.5 times the control value. The results reported the enhanced cell viability in 2D conditions, and 3D culture with bone tissue spheroids (viability was almost 150%). Furthermore, alkaline phosphatase activity (ALP) was tested in both monolayer and spheroid conditions, and the results indicated a boosted ALP activity in 2D and 3D condition (4 and 2 times the control value respectively). Additionally, nanocomposite powder extracts promoted the expression of both the COL1 and VEGF genes in 3D cultures (5 and 1.5 times the first day value respectively), showing the extract capability in accelerating bone spheroid formation. The current proof-of-concept study showed that 3D culture technology could provide a valuable way to understand the potential of tissue engineering before undertaking costly and harsh animal studies.

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.

Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses. [ABSTRACT FROM AUTHOR]

Abstract Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH.

Hydrogel-based bio-inks have been extensively used for developing three-dimensional (3D) printed biomaterials for biomedical applications. However, poor mechanical performance and the inability to conduct electricity limit their application as wearable sensors. In this work, we formulate a novel, 3D printable electro-conductive hydrogel consisting of silicate nanosheets (Laponite), graphene oxide, and alginate. The result generated a stretchable, soft, but durable electro-conductive material suitable for utilization as a novel electro-conductive bio-ink for the extrusion printing of different biomedical platforms, including flexible electronics, tissue engineering, and drug delivery. A series of tensile tests were performed on the material, indicating excellent stability under significant stretching and bending without any conductive or mechanical failures. Rheological characterization revealed that the addition of Laponite enhanced the hydrogel’s mechanical properties, including stiffness, shear-thinning, and stretchability. We also illustrate the reproducibility and flexibility of our fabrication process by extrusion printing various patterns with different fiber diameters. Developing an electro-conductive bio-ink with favorable mechanical and electrical properties offers a new platform for advanced tissue engineering.

Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

Glioblastoma multiforme (GBM) is a rapidly progressive and deadly form of brain tumor with a median survival rate of ~15 months. GBMs are hard to treat and significantly affect the patient’s physical and cognitive abilities and quality of life. Temozolomide (TMZ)—an alkylating agent that causes DNA damage—is the only chemotherapy choice for the treatment of GBM. However, TMZ also induces autophagy and causes tumor cell resistance and thus fails to improve the survival rate among patients. Here, we studied the drug-induced programmed cell death and invasion inhibition capacity of TMZ and a mevalonate cascade inhibitor, simvastatin (Simva), in a three-dimensional (3D) microfluidic model of GBM. We elucidate the role of autophagy in apoptotic cell death by comparing apoptosis in autophagy knockdown cells (Atg7 KD) against their scrambled counterparts. Our results show that the cells were significantly less sensitive to drugs in the 3D model as compared to monolayer culture systems. An immunofluorescence analysis confirmed that apoptosis is the mechanism of cell death in TMZ- and Simva-treated glioma cells. However, the induction of apoptosis in the 3D model is significantly lower than in monolayer cultures. We have also shown that autophagy inhibition (Atg7 KD) did not change TMZ and Simva-induced apoptosis in the 3D microfluidic model. Overall, for the first time in this study we have established the simultaneous detection of drug induced apoptosis and autophagy in a 3D microfluidic model of GBM. Our study presents a potential ex vivo platform for developing novel therapeutic strategies tailored toward disrupting key molecular pathways involved in programmed cell death and tumor invasion in glioblastoma.