Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves

The Integration of Nanotechnology and Biology for Cell Engineering: Promises and Challenges

Introduction: Successful tissue engineering strategies leading to the regeneration of a tissue depend on many factors, starting from the choice of appropriate scaffold material, tailoring the surface functionalities and topography, providing the correct amount of chemical and mechanical stimuli at the appropriate time points, and ensuring the uniform and precise localization of cells. Further challenges arise when more than one cell type has to be employed for the effective regeneration of an organ. Importance: Though the use of nanomaterials has improved tissue engineering, many pitfalls still exist that present a roadblock in the translation of tissue engineering strategies to clinical practice. Apart from employing different materials with distinct surface functionalities and mechanical properties, various strategies have been employed to manipulate the surface topography and chemistry of scaffolds to create a biomimetic microenvironment for effective tissue regeneration. Conclusion: This review provides information about the factors influencing tissue engineering, namely geometry, chemistry, mechanics and cells, and the emerging concepts that may well represent the future of regenerative medicine. Electrospinning techniques and their variants, self-assembly, cell-printing techniques and cell sheet engineering, have all been elaborated in detail. These novel techniques may serve to overcome the challenges currently faced in tissue engineering

“Nano”: an emerging avenue in electrochemical detection of neurotransmitters

The growing importance of nanomaterials toward the detection of neurotransmitter molecules has been chronicled in this review. Neurotransmitters (NTs) are chemicals that serve as messengers in synaptic transmission and are key players in brain functions. Abnormal levels of NTs are associated with numerous psychotic and neurodegenerative diseases. Therefore, their sensitive and robust detection is of great significance in clinical diagnostics. For more than three decades, electrochemical sensors have made a mark toward clinical detection of NTs. The superiority of these electrochemical sensors lies in their ability to enable sensitive, simple, rapid, and selective determination of analyte molecules while remaining relatively inexpensive. Additionally, these sensors are capable of being integrated in robust, portable, and miniaturized devices to establish point-of-care diagnostic platforms. Nanomaterials have emerged as promising materials with significant implications for electrochemical sensing due to their inherent capability to achieve high surface coverage, superior sensitivity, and rapid response in addition to simple device architecture and miniaturization. Considering the enormous significance of the levels of NTs in biological systems and the advances in sensing ushered in with the integration of nanotechnology in electrochemistry, the analysis of NTs by employing nanomaterials as interface materials in various matrices has emerged as an active area of research. This review explores the advancements made in the field of electrochemical sensors for the sensitive and selective determination of NTs which have been described in the past two decades with a distinctive focus on extremely innovative attribut,es introduced by nanotechnology

Phosphoproteomics of retinoblastoma:A pilot study identifies aberrant kinases

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer. Over 350 proteins showed differential phosphorylation in RB compared to control retina. Our study identified stress response proteins to be hyperphosphorylated in RB which included H2A histone family member X (H2AFX) and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma, which indicated the activation of DNA damage response pathways. We also observed the activation of anti-apoptosis in retinoblastoma compared to control. These observations showed the activation of survival pathways in retinoblastoma. The identification of hyperphosphorylated protein kinases including Bromodomain containing 4 (BRD4), Lysine deficient protein kinase 1 (WNK1), and Cyclin-dependent kinase 1 (CDK1) in RB opens new avenues for the treatment of RB. These kinases can be considered as probable therapeutic targets for RB, as small-molecule inhibitors for some of these kinases are already in clinical trials for the treatment other cancers

Artificial Intelligence-Driven Diagnosis of Pancreatic Cancer

Pancreatic cancer is among the most challenging forms of cancer to treat, owing to its late diagnosis and aggressive nature that reduces the survival rate drastically. Pancreatic cancer diagnosis has been primarily based on imaging, but the current state-of-the-art imaging provides a poor prognosis, thus limiting clinicians’ treatment options. The advancement of a cancer diagnosis has been enhanced through the integration of artificial intelligence and imaging modalities to make better clinical decisions. In this review, we examine how AI models can improve the diagnosis of pancreatic cancer using different imaging modalities along with a discussion on the emerging trends in an AI-driven diagnosis, based on cytopathology and serological markers. Ethical concerns regarding the use of these tools have also been discussed

(2RS,5′RS)-3′,4′-Bis(4-chlorophenyl)-3,4-dihydrospiro[acridine-2,5′(4′H)-[1,2]oxazol]-1(2H)-one

The title compound, C27H18Cl2N2O2, represents a racemic mixture of the corresponding R,R and S,S diastereomers. The isoxazoline ring adopts an envelope conformation with the spiro C atom deviating by 0.093 (2) Å from the rest of the ring. The six-membered keto-substituted carbocycle has a sofa conformation with the methylene C atom adjacent to the spiro center deviating by 0.289 (2) Å from the mean plane of the remaining atoms. In the crystal, molecules are linked via C—H...Cl interactions and C—Cl...O halogen bonds [2.958 (2) Å, 171.39 (7)°], which generate bifurcated R21(6) ring motifs resulting in C21[R21(6)] chains running parallel to [010]

In Vivo Biocompatibility of PLGA-Polyhexylthiophene Nanofiber Scaffolds in a Rat Model

Electroactive polymers have applications in tissue engineering as a physical template for cell adhesion and carry electrical signals to improve tissue regeneration. Present study demonstrated the biocompatibility and biodegradability of poly(lactide-co-glycolide)-poly(3-hexylthiophene) (PLGA-PHT) blend electrospun scaffolds in a subcutaneous rat model. The biocompatibility of PLGA-undoped PHT, PLGA-doped PHT, and aligned PLGA-doped PHT nanofibers was evaluated and compared with random PLGA fibers. The animals were sacrificed at 2, 4, and 8 weeks; the surrounding tissue along with the implant was removed to evaluate biocompatibility and biodegradability by histologic analysis and GPC, respectively. Histology results demonstrated that all scaffolds except PLGA-undoped PHT showed decrease in inflammation over time. It was observed that the aligned PLGA-doped PHT fibers elicited moderate response at 2 weeks, which further reduced to a mild response over time with well-organized tissue structure and collagen deposition. The degradation of aligned nanofibers was found to be very slow when compared to random fibers. Further, there was no reduction in the molecular weight of undoped form of PHT throughout the study. These experiments revealed the biocompatibility and biodegradability of PLGA-PHT nanofibers that potentiate it to be used as a biomaterial for various applications

Nanoimmunotherapy – cloaked defenders to breach the cancer fortress

Cancer continues to be ranked among the top causes of mortality in the world despite the advances made in science and technology. The sub-par performance of cancer therapeutic strategies is due to the transformation of the cancer from a proliferating mass of cells into an impregnable fortress that manipulates and controls the microenvironment to prevent access to any potential cytotoxic factor as well as circumvent the innate immune surveillance processes. Recruitment of the native immune cells to selectively recognize and kill cancer cells can serve to augment the cytotoxic effects of conventional cancer therapeutic approaches. In addition to annihilation of the cancer cells, the induction of memory in the immune cells prevents the possibility of cancer recurrence. However, despite the apparent benefits of cancer immunotherapy, there are several pitfalls that need to be addressed in order to extend these benefits to the clinic. In this context, engineered nanostructured carrier systems can be effectively employed for an activation and priming of the host immune system selectively against the target cancer cells. This has led to the emergence of “nanoimmunotherapy” as an important therapeutic approach against cancer. The use of multi-functional nanomaterials in combination with immunotherapy offers possible solutions to overcome the current limitations in cancer therapy and represents the next generation of “smart therapeutics,” which forms the prime focus of discussion in this review