Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a short half‐life, and its physiology role is concentration dependent, often restricting its function to a target site. Providing NO from an external source is beneficial in promoting cellular functions and treatment of different pathological conditions. Hence, the multifaceted role of NO in physiology and pathology has garnered massive interest in developing strategies to deliver exogenous NO for the treatment of various regenerative and biomedical complexities. NO‐releasing platforms or donors capable of delivering NO in a controlled and sustained manner to target tissues or organs have advanced in the past few decades. This review article discusses in detail the generation of NO via the enzymatic functions of NO synthase as well as from NO donors and the multiple biological and pathological processes that NO modulates. The methods for incorporating of NO donors into diverse biomaterials including physical, chemical, or supramolecular techniques are summarized. Then, these NO‐releasing platforms are highlighted in terms of advancing treatment strategies for various medical problems.
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss and cognitive impairment, thereby disrupting the performance of daily activities. Numerous therapeutics have shown efficacy in animal AD models but failed in human patients. The key to understanding the etiology of AD lies in the development of effective disease models, which can ideally recapitulate all characteristics of the disease. Over the years, different approaches including in vitro, in vivo, and in silico models are able to resemble certain features of AD. In this review, the significance of different in vitro models including their merits and limitations in modeling AD is discussed, which will give a better perspective on the development of a comprehensive model that can mimic human AD. This starts with a brief introduction to AD and its pathology. Then it mainly focuses on the two‐dimensional, three‐dimensional and microfluidic in vitro models of AD that have made significant advancements in understanding AD pathology and aiding in screening effective therapeutics. Several 3D neural tissue engineering models developed in the last two decades along with a discussion on the future prospects in the development of efficient in vitro AD models are further highlighted.
Copper high aspect ratio structures (CuHARS) and silver cystine nanoparticles (AgCysNPs) are two unique micro/nano particles under study here that show extensive anti-cancer effects on a glioma tumor cell line. These micro/nano particles have shown potent toxicity in the presence of inflammatory stimulus (combination of tumor necrosis factor, [TNF] and lipo-polysaccharide, LPS). CuHARS with a concentration of 20 μg/ml uniquely increased the catalytic generation of nitric oxide (NO), an important contributor in the immune system. This NO was generated in a cell culture tumor microenvironment (TME) in the presence of 25 µM S-nitrosothiol (cysteine-NO) and the inflammatory stimulus. CuHARS increased the NO production by 68.75% when compared to untreated glioma cells with CysNO and inflammatory stimulus. The production of NO was significantly higher under similar circumstances in the case of normal primary structural cells like brain microvascular endothelial cells (BMVECs). The production of NO by BMVECs went up by 181.25% compared to glioma cells. This significant increase in the NO concentration could have added up to tumorigenesis but the anti-cancer effect of CuHARS was prominent enough to lower down the viability of glioma cells by approximately 20% and increased the metabolism of structural cells, BMVECs by approximately 200%. The immunomodulatory effect of NO in the TME under these circumstances in the presence of the novel micro/nano material, CuHARS has risen up compared to the effect of inflammatory stimulus alone. The potency and specific nature of these materials toward tumor cells may make them suitable candidates for cancer treatment. Successive treatment of CuHARS to glioma cells also proved to be an effective approach considering the decrease in the total count of cells by 11.84 fold in case of three successive treatments compared to a single dose which only decreased the cell count by 2.45 fold showing the dose-dependent increasing toxicity toward glioma cells. AgCysNPs are another potent nanomaterial which also proved its significant toxic nature toward tumor cell lines as demonstrated here, but their immunomodulatory response is still unclear and needs to be explored further.
Electrostatic flocking is a textile technology that employs a Coulombic driving force to launch short fibers from a charging source towards an adhesive-covered substrate, resulting in a dense array of aligned fibers perpendicular to the substrate. However, electrostatic flocking of insulative polymeric fibers remains a challenge due to their insufficient charge accumulation. We report a facile method to flock electrostatically insulative poly(ε-caprolactone) (PCL) microfibers (MFs) and electrospun PCL nanofiber yarns (NFYs) by incorporating NaCl during pre-flock processing. Both MF and NFY were evaluated for flock functionality, mechanical properties, and biological responses. To demonstrate this platform's diverse applications, standalone flocked NFY and MF scaffolds were synthesized and evaluated as scaffold for cell growth. Employing the same methodology, scaffolds made from poly(glycolide-co-l-lactide) (PGLA) (90:10) MFs were evaluated for their wound healing capacity in a diabetic mouse model. Further, a flock-reinforced polydimethylsiloxane (PDMS) disc was fabricated to create an anisotropic artificial vertebral disc (AVD) replacement potentially used as a treatment for lumbar degenerative disc disease. Overall, a salt-based flocking method is described with MFs and NFYs, with wound healing and AVD repair applications presented.