Novel Bone Void Filling Cement Compositions Based on Shell Nacre and Siloxane Methacrylate Resin: Development and Characterization

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research regarding using shell nacre powder as a cement with improved biological and physicochemical properties. To address this, bone void filling cement was formulated by incorporating shell nacre powder and an organically modified ceramic resin (ormocer). The shell nacre powder was specifically processed from the shells of Pinctada fucata and analysed using thermogravimetric analysis (TGA), X-ray diffraction spectroscopy, Fourier transform infrared (FTIR), and Raman spectroscopy, confirming the presence of organic constituents and inorganic aragonite. Trace element analysis confirmed the eligibility of shell nacre powder for biomedical applications. Next, the ormocer SNLSM2 was synthesized through a modified sol–gel method. FTIR, Raman, TGA, and transmission electron microscopy studies revealed the presence of a ladder-structured siloxane backbone and methacrylate side chain. To develop chemical curable composite shell nacre cement (SNC), different amounts of shell nacre (24%, 48%, and 72%) were added to the SNLSM2 resin, and the impact on the physicochemical properties of the cement was studied. Among the compositions, SNC 72 exhibited significantly lower linear polymerization shrinkage (0.4%) and higher compressive (>100 MPa) and flexural strength (>35 MPa). SNC 72 was radiopaque, and the exotherm generated during the cement curing was minimal. Cytotoxicity studies with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the findings of this study prove that the shell nacre cement is a promising candidate for managing bone voids

Simultaneous synthesis of carbon quantum dots, fluorescent probes, biofilms and hydrochar from sustainable vermicompost for versatile applications

Sustainable and renewable sources of nanomaterial synthesis are a demanding approach. This work provides new insight into the versatile applications of materials derived from vermicompost. The report explains the simultaneous conversion of vermicompost to hydrophilic and stable carbon quantum dots (CDs) and hydrochar. The as-prepared CDs exhibit broad range emission spectrum from blue (400) to red (600 nm) with excitation dependent emission phenomenon. The films prepared using the CDs showed higher cellular uptake and intracellular localization. The FTIR results supported the existence of hydroxyl, amine, carboxylate and carbonyl groups on the surfaces of the CD. The zeta potential value of CDs was − 38.5. The ion absorption was tested for different cations and was maximum for Fe3+ ions, even for micromolar solutions. The hydrochar produced was used for adsorption of methylene blue dye from water and it was found that 80% of dye was removed after 12 h. of treatment. Thus, we suggest vermicompost as a promising alternative for nanomaterial synthesis

Contact Guidance Mediated by Hybrid Thread Topography Enhances Osseointegration of As-machined Ti6Al4V Dental Implant.

Purpose The main objective of this study is to investigate the key role of as-machined implant design features on the osseointegration. The bone regeneration ability of the newly developed Ti6Al4V hybrid threaded tapered implant without any surface modification has been validated and benchmarked against Straumann® implant (control) in the rabbit model for 12 weeks. Material and Methods The test and control implants were implanted in the femur medial condyle of twelve adult New Zealand white rabbits on the contralateral limbs; each femoral medial condyle received a test or control implant randomly. The bone formation and osseointegration around the implants were assessed qualitatively and quantitatively using histology, micro-computed tomography (Micro-CT), molecular gene studies, and histomorphometric analysis after 12 weeks of implantation. Results The overall assessment suggests homogenous and continuous neobone formation and osseointegration around the hybrid threads of the test implants. Superior bone-to-implant contact percentage (BIC) was observed in the case of hybrid threaded test implants with an average value of 80.8%, compared to 67.1% for the control implant. Upregulated expression of osteogenic (COL1A1, RUNX2, SPARC, and SPP1) and angiogenic (VEGF) genes in the case of test implant indicates better coupled osseointegrationa and angiogenesis. Conclusion It can be concluded that the extent of neobone formation and expression of the osteogenic/angiogenic genes is positively correlated with optimal design features of the implant, which leads to the contact guidance of the osteoblasts on the implant surface. The study also advocates that the novel tapered multithreaded implant design concept alone, without any surface modification, can facilitate osseointegration in a manner better than clinically used surface-modified implants. Lay Summary Dental implants are artificial tooth roots and are used to treat complete or partial toothlessness. The new implant design concept reported here is expected to support both soft tissue and hard tissue attachment and to improve primary stability. This study unraveled the effect of the novel external hybrid thread design on the implant integration with the surrounding bone. This aspect was validated in the rabbit model and benchmarked against the commercially available Straumann® implant. This study has unambiguously demonstrated the ability of as-machined Ti implants to facilitate better new bone and new blood vessels formation than the commercial implant

Fluorescent carbon dots tailored iron oxide nano hybrid system for in vivo optical imaging of liver fibrosis

Hybrid nanoparticles are innovative invention of last decade designed to overcome limitations of single-component nanoparticles by introducing multiple functionalities through combining two or more different nanoparticles. In this study, we are reporting development of magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbon nanoparticles to enablein vivofluorescence imaging which also has all the required characteristic properties to use as Magnetic Resonance Imaging (MRI) contrast agent. In order to achieve dual-functional imaging, alginate and pullulan coated super paramagnetic iron oxide nanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesised separately. ASPIONs and PSPIONs were further chemically conjugated with Cdts and developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts. Subsequently, evaluation of the materials for its size, functionalisation efficiency, fluorescence and magnetic properties, biocompatibility and cellular uptake efficiency has been carried out. Fluorescence imaging of liver fibrosis was performedin vivoin rodent model of liver fibrosis using the two nanohybrids, which is further confirmed by high fluorescence signal from the harvested liver

Bifunctional cysteine gold nanocluster for β-amyloid fibril inhibition and fluorescence imaging: A distinctive approach to manage Alzheimer's disease

Alzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to β-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD

Blood brain barrier-on-a-chip to model neurological diseases

The blood-brain barrier (BBB) is a vital and unique multi-dimensional selective barrier that helps maintain brain homeostasis. BBB is a complex and dynamic structure responsible for regulating the transport of ions and molecules. BBB contains several transporter proteins and tight junctions (TJs) that control the passage of nutrients, while protecting the brain from hazardous toxins and pathogens. Neurological diseases are the primary cause of disability and are considered the second-largest cause of death. BBB dysfunction reduce blood flow and will also permit the entry of toxic substances, and microbial agents in to the brain. This impairment of BBB has been associated with various neurodegenerative diseases. In vitro models that can provide an accurate and deep understanding of neurological disease progression and drug discovery are excellent options.Advancement in microfluidic in vitro models opened new opportunities to study human cell behaviour relative to physiological importance.The limitation of both static transwell and conventional in vitro models was addressed by developing a microfluidic BBB. The microfluidic system showed a close resemblance to the BBB in vivo. The neuronal transport processes and neurogenesis mechanism was well understood with simple neuronal networks. More complex three-dimensional models with multiple cell types, such as Organ on-chip systems, enabled a new platform for a better understanding of the disease and mimicking the physiological conditions. The structure of the blood-brain barrier, conventional models used to model BBB, recent developments in the BBB model using microfluidic technology and the relevance of microfluidic technology in neurological disease modeling is portrayed through this review

Multifunctional amino functionalized graphene quantum dots wrapped upconversion nanoparticles for photodynamic therapy and X-ray CT imaging.

Herein, we designed and developed a multifunctional nanocomposites by complexing NaGdF4:Yb/Er nanoparticles (UCNPs) with amino functionalized graphene quantum dots (af-GQDs). In the as-prepared nanocomposite (af-GQD/UCNPs), properties of UCNPs and af-GQDs were incorporated into a single nanoplatform to endow therapeutic and diagnostic functions. The UCNPs were employed as an imaging probe and a contrast agent for CT imaging, and the af-GQDs served as a therapeutic agent and photosensitizer (PS) by generating singlet oxygen for photodynamic therapy (PDT). Furthermore, the nanocomposites were investigated by electron microscopy, FTIR spectroscopy, zeta potential measurement, UV–vis spectroscopy, upconversion luminescence measurement, and cytotoxicity assessment. The in vitro experiments displayed excellent X-ray attenuation ability and PDT effects of af-GQD/UCNPs. Hence, the proposed multifunctional nanocomposites, which possesses upconversion luminescence, photodynamic, and X-ray attenuation properties, might be a viable option for application in bio-imaging and photodynamic therapy

Antineoplastic effects of cassava-cyanide extract on human glioblastoma (LN229) cells

Several natural compounds reduce tumour cell growth and metastasis by inducing programmed cell death. Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides such as, linamarin and lotaustralin, can be enzymatically cleaved by linamarase to release hydrogen cyanide (HCN), which can have therapeutic benefits against hypertension, asthma, and cancer. We have developed a technology for isolating bio-active principles from cassava leaves.The present study is designed to analyze the cytotoxic effect of cassava cyanide extract (CCE) against human glioblastoma cells (LN229). The treatment of CCE demonstrated a dose dependent toxicity on glioblastoma cells. At higher concentration tested, the CCE (400 μg/mL) was found to be cytotoxic, reducing the cell viability to 14.07 ± 2.15% by negatively influencing the mitochondrial activity, and lysosomal and cytoskeletal integrity. Coomassie's brilliant blue staining confirmed cells' morphological aberration after 24 h of treatment with CCE. Moreover, DCFH-DA assay and Griess reagent showed an increase in ROS but a decrease in RNS production at a concentration of CCE. Flow cytometry analysis revealed that CCE interfered with G0/G1, S, and G2/M stages of the cell cycle of glioblastoma, and Annexin/PI staining indicated a dose-dependent increase in cell death, confirming the toxic nature of CCE on LN229 cells. These findings suggest that cassava cyanide extract has potential as an antineoplastic agent against glioblastoma cells, which is an aggressive and difficult-to-treat type of brain cancer. However, it is important to note that the study was conducted in vitro, and further research is necessary to assess the safety and efficacy of CCE in vivo. Additionally, it is essential to establish the optimal dose and potential side effects before considering its use as a therapeutic agent

Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review

Microfluidics is a revolutionary technology that has promising applications in the biomedical field.Integrating microfluidic technology with the traditional assays unravels the innumerable possibilities for translational biomedical research. Microfluidics has the potential to build up a novel platform for diagnosis and therapy through precise manipulation of fluids and enhanced throughput functions. The developments in microfluidics-based devices for diagnostics have evolved in the last decade and have been established for their rapid, effective, accurate and economic advantages. The efficiency and sensitivity of such devices to detect disease-specific macromolecules like proteins and nucleic acids have made crucial impacts in disease diagnosis. The disease modelling using microfluidic systems provides a more prominent replication of the in vivo microenvironment and can be a better alternative for the existing disease models. These models can replicate critical microphysiology like the dynamic microenvironment, cellular interactions, and biophysical and biochemical cues. Microfluidics also provides a promising system for high throughput drug screening and delivery applications. However, microfluidics-based diagnostics still encounter related challenges in the reliability, real-time monitoring and reproducibility that circumvents this technology from being impacted in the healthcare industry. This review highlights the recent microfluidics developments for modelling and diagnosing common diseases, including cancer, neurological, cardiovascular, respiratory and autoimmune disorders, and its applications in drug development

Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells

Ketamine is generally a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long-term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long-term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN-229 cells in a dose-dependent manner. According to the cell viability assays, there is a dose-dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro-inflammatory cytokine (interleukin [IL]-β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long-term exposure rather than a single exposure as an anesthetic agent