Impact of the Reduction Time-Dependent Electrical Conductivity of Graphene Nanoplatelet-Coated Aligned Bombyx mori Silk Scaffolds on Electrically Stimulated Axonal Growth.

Graphene-based nanomaterials, renowned for their outstanding electrical conductivity, have been extensively studied as electroconductive biomaterials (ECBs) for electrically stimulated tissue regeneration. However, using eco-friendly reducing agents like l-ascorbic acid (l-Aa) can result in lower conductive properties in these ECBs, limiting their full potential for smooth charge transfer in living tissues. Moreover, creating a flexible biomaterial scaffold using these materials that accurately mimics a specific tissue microarchitecture, such as nerves, poses additional challenges. To address these issues, this study developed a microfibrous scaffold of Bombyx mori (Bm) silk fibroin uniformly coated with graphene nanoplatelets (GNPs) through a vacuum coating method. The scaffold's electrical conductivity was optimized by varying the reduction period using l-Aa. The research systematically investigated how different reduction periods impact scaffold properties, focusing on electrical conductivity and its significance on electrically stimulated axonal growth in PC12 cells. Results showed that a 48 h reduction significantly increased surface electrical conductivity by 100-1000 times compared to a shorter or no reduction process. l-Aa contributed to stabilizing the reduced GNPs, demonstrated by a slow degradation profile and sustained conductivity even after 60 days in a proteolytic environment. ß (III) tubulin immunostaining of PC12 cells on varied silk:GNP scaffolds under pulsed electrical stimulation (ES, 50 Hz frequency, 1 ms pulse width, and amplitudes of 100 and 300 mV/cm) demonstrates accelerated axonal growth on scaffolds exhibiting higher conductivity. This is supported by upregulated intracellular Ca2+ dynamics immediately after ES on the scaffolds with higher conductivity, subjected to a prolonged reduction period. The study showcases a sustainable reduction approach using l-Aa in combination with natural Bm silk fibroin to create a highly conductive, mechanically robust, and stable silk:GNP-based aligned fibrous scaffold. These scaffolds hold promise for functional regeneration in electrically excitable tissues such as nerves, cardiac tissue, and muscles.

Protein Kinase C (PKC)-mediated TGF-ß Regulation in Diabetic Neuropathy: Emphasis on Neuro-inflammation and Allodynia.

According to the World Health Organization (WHO), diabetes has been increasing steadily over the past few decades. In developing countries, it is the cause of increased morbidity and mortality. Diabetes and its complications are associated with education, occupation, and income across all levels of socioeconomic status. Factors, such as hyperglycemia, social ignorance, lack of proper health knowledge, and late access to medical care, can worsen diabetic complications. Amongst the complications, neuropathic pain and inflammation are considered the most common causes of morbidity for common populations. This review is focused on exploring protein kinase C (PKC)-mediated TGF-ß regulation in diabetic complications with particular emphasis on allodynia. The role of PKC-triggered TGF-ß in diabetic neuropathy is not well explored. This review will provide a better understanding of the PKC-mediated TGF-ß regulation in diabetic neuropathy with several schematic illustrations. Neuroinflammation and associated hyperalgesia and allodynia during microvascular complications in diabetes are scientifically illustrated in this review. It is hoped that this review will facilitate biomedical scientists to better understand the etiology and target drugs effectively to manage diabetes and diabetic neuropathy.

Assessing the relationship between hypospadias risk and parental occupational exposure to potential endocrine-disrupting chemicals.

OBJECTIVE: The association between periconceptional parental exposure to endocrine-disrupting chemicals (EDCs) and hypospadias remains inconclusive and controversial. Therefore, we conducted a hospital-based retrospective study to assess the relationship between hypospadias risk and parental occupational exposure to potential EDCs. METHODS: Incident cases (n=73) were boys between 0 and 14 years diagnosed with hypospadias with no micropenis or cryptorchidism. Controls (n=146) were an age-matched group of boys without any congenital malformations, inguinal hernia, nephrological, urological and genital disorders. Their selection was independent of exposures to EDCs. Data on parental occupation and sociodemographic variables were collected using a structured questionnaire. We evaluated parental occupational exposures using a previously validated job-exposure matrix (JEM) for EDCs. RESULTS: In our case-control study, 30.1% of all pregnancies had likely exposure to potential EDCs. The most prevalent occupations conferring possible exposure were related to activities on farms. Maternal and paternal occupational exposure to potential EDCs significantly increased the risk of mild hypospadias than moderate-to-severe hypospadias (OR=6.55 vs OR=4.63). Among various categories, parental occupational exposure to pesticides was associated with at least a twofold increased risk of hypospadias. Maternal EDC exposure during the first trimester significantly increased the risk of bearing a hypospadiac child (OR=4.72 (95% CI 2.10 to 10.60)). CONCLUSION: This study suggests that EDCs are a risk factor for hypospadias through occupational exposure during fetal life.

Surface Functionalized Polyaniline Nanofibers:Chitosan Nanocomposite for Promoting Neuronal-like Differentiation of Primary Adipose Derived Mesenchymal Stem Cells and Urease Activity.

Bioscaffolds having electrically conducting polymers (CPs) have become increasingly relevant in tissue engineering (TE) because of their ability to regulate conductivity and promote biological function. With this in mind, the current study shows a conducting polyaniline nanofibers (PNFs) dispersed chitosan (Ch) nanocomposites scaffold with a simple one-step surface functionalization approach using glutaraldehyde for potential neural regeneration applications. According to the findings, 4 wt % PNFs dispersion in Ch matrix is an optimal concentration for achieving desirable biological functions while maintaining required physicochemical properties as evidenced by SEM, XRD, current-voltage (I-V) measurement, mechanical strength test, and in vitro biodegradability test. Surface chemical compositional analysis using XPS and ATR FT-IR confirms the incorporation of aldehyde functionality after functionalization, which is corroborated by surface energy calculations following the Van Oss-Chaudhury-Good method. Surface functionalization induced enhancement in surface hydrophilicity in terms of the polar component of surface energy (γiAB) from 6.35 to 12.54 mN m-1 along with an increase in surface polarity from 13.61 to 22.54%. Functionalized PNF:Ch scaffolds demonstrated improvement in enzyme activity from 67 to 94% and better enzyme kinetics with a reduction of Michaelis constants (Km) from 21.55 to 13.81 mM, indicating favorable protein-biomaterial interactions and establishing them as biologically perceptible materials. Surface functionalization mediated improved cell-biomaterial interactions led to improved viability, adhesion, and spreading of primary adipose derived mesenchymal stem cells (ADMSCs) as well as improved immunocompatibility. Cytoskeletal architecture assessment under differentiating media containing 10 ng/mL of each basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) revealed significant actin remodeling with neurite-like projections on the functionalized scaffolds after 14 days. Immunocytochemistry results showed that more than 85% of cells expressed early neuron specific ß III tubulin protein on the functionalized scaffolds, whereas glial fibrillary acidic protein (GFAP) expression was limited to approximately 40% of cells. The findings point to the functionalized nanocomposites' potential as a smart scaffold for electrically stimulated neural regeneration, as they are flexible enough to be designed into microchanneled or conduit-like structures that mimic the microstructures and mechanical properties of peripheral nerves.