Noninvasive Delivery of Self-Regenerating Cerium Oxide Nanoparticles to Modulate Oxidative Stress in the Retina.

Diseases affecting the retina, such as age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and retinal vein occlusions, are currently treated by the intravitreal injection of drug formulations. These disease pathologies are driven by oxidative damage due to chronic high concentrations of reactive oxygen species (ROS) in the retina. Intravitreal injections often induce retinal detachment, intraocular hemorrhage, and endophthalmitis. Furthermore, the severe eye pain associated with these injections lead to patient noncompliance and treatment discontinuation. Hence, there is a critical need for the development of a noninvasive therapy that is effective for a prolonged period for treating retinal diseases. In this study, we developed a noninvasive cerium oxide nanoparticle (CNP) delivery wafer (Cerawafer) for the modulation of ROS in the retina. We fabricated Cerawafer loaded with CNP and determined its SOD-like enzyme-mimetic activity and ability to neutralize ROS generated in vitro. We demonstrated Cerawafer's ability to deliver CNP in a noninvasive fashion to the retina in healthy mouse eyes and the CNP retention in the retina for more than a week. Our studies have demonstrated the in vivo efficacy of the Cerawafer to modulate ROS and associated down-regulation of VEGF expression in the retinas of very-low-density lipoprotein receptor knockout (vldlr-/-) mouse model. The development of a Cerawafer nanotherapeutic will fulfill a hitherto unmet need. Currently, there is no such therapeutic available, and the development of a Cerawafer nanotherapeutic will be a major advancement in the treatment of retinal diseases.

3D Printing of MgAl2O4 Spinel Mesh and Densification Through Pressure-Less Sintering and Hot Isostatic Pressing.

MgAl2O4 spinel mesh with micro-features of 410 and 250 µm unit cell length and rib thickness, respectively, was three-dimensional (3D) printed and sintered followed by Hot Isostatic Pressing (HIPing). A stable colloidal dispersion of spinel in polymer-water solution was prepared and 3D-printed using a 30-gauge needle (∼100 µm inner diameter) on a regenHU 3D-Discovery bioprinter. Samples were characterized for their density and microstructure. Samples with near theoretical density after HIPing was subjected to mechanical property evaluation such as hardness by Vickers indentation and elastic modulus using nanoindentation technique. Microstructure of sintered samples across the ribs have shown graded grain structure with finer grains near the edges (0.7 µm average) with occasional porosity and coarser grains toward the center of the rib (5.2 µm average). HIPing resulted in substantial grain growth and the average grain size was found to be 10.9 µm (with a variation in the grain size of 2.2 µm along the edges and 13.1 µm at the center of the rib) exhibiting close packed and dense microstructure. Finer grains toward the edges may probably be due to the flow behavior during printing process and lower distribution of the powder loading along the edges resulting in low green density. This relatively higher porosity pining the grain growth under the extremely low heating rate employed for the controlled shrinkage to maintain the integrity of the sample. 3D printed samples after HIPing exhibited a density of 3.57 g/cc and hardness of 12.95 GPa, which are at par with the samples processed through conventional ceramic processing techniques. Nanoindentation studies employing maximum load of 45 mN with depth have shown an elastic modulus of 238 ± 15 GPa. MgAl2O4 spinel mesh 3D printed in this study is a potential prospective candidate that can be explored for cranioplasty procedures and other biomedical applications.

Dextran Sulfate Polymer Wafer Promotes Corneal Wound Healing.

Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid clearance from the ocular surface or due to drug-related side effects such as cataract formation or increased intraocular pressure. In this article, we presented the development of a dextran sulfate-based polymer wafer (DS-wafer) for the effective modulation of inflammation and fibrosis and demonstrated its efficacy in two corneal injury models: corneal abrasion mouse model and alkali induced ocular burn mouse model. The DS-wafers were fabricated by the electrospinning method. We assessed the efficacy of the DS-wafer by light microscopy, qPCR, confocal fluorescence imaging, and histopathological analysis. These studies demonstrated that the DS-wafer treatment is significantly effective in modulating corneal inflammation and fibrosis and inhibited corneal scarring and opacification compared to the unsulfated dextran-wafer treated and untreated corneas. Furthermore, these studies have demonstrated the efficacy of dextran sulfate as an anti-inflammatory and antifibrotic polymer therapeutic.

Structure, Properties and Applications of Two-Dimensional Hexagonal Boron Nitride.

Hexagonal boron nitride (h-BN) has emerged as a strong candidate for two-dimensional (2D) material owing to its exciting optoelectrical properties combined with mechanical robustness, thermal stability, and chemical inertness. Super-thin h-BN layers have gained significant attention from the scientific community for many applications, including nanoelectronics, photonics, biomedical, anti-corrosion, and catalysis, among others. This review provides a systematic elaboration of the structural, electrical, mechanical, optical, and thermal properties of h-BN followed by a comprehensive account of state-of-the-art synthesis strategies for 2D h-BN, including chemical exfoliation, chemical, and physical vapor deposition, and other methods that have been successfully developed in recent years. It further elaborates a wide variety of processing routes developed for doping, substitution, functionalization, and combination with other materials to form heterostructures. Based on the extraordinary properties and thermal-mechanical-chemical stability of 2D h-BN, various potential applications of these structures are described.

3D-Bioprinted Inflammation Modulating Polymer Scaffolds for Soft Tissue Repair.

Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented. The bioscaffold design is based on the idea that, if the excess proinflammatory cytokines are sequestered from the site of injury by the surgical implantation of a bioscaffold, the inflammatory response can be modulated, and the visceral adhesion formations and postsurgical complications can be minimized. The bioscaffold is fabricated by 3D-bioprinting of an in situ phosphate crosslinked poly(vinyl alcohol) polymer. In vivo efficacy of the bioscaffold is evaluated in a rat ventral hernia model. In vivo proinflammatory cytokine expression analysis and histopathological analysis of the tissues have confirmed that the bioscaffold acts as an inflammation trap and captures the proinflammatory cytokines secreted at the implant site and effectively modulates the local inflammation without the need for exogenous anti-inflammatory agents. The bioscaffold is very effective in inhibiting visceral adhesions formation and minimizing postsurgical complications.

Multifunctional Bio-Nanocomposite Coatings for Perishable Fruits.

Hunger and chronic undernourishment impact over 800 million people, which translates to ≈10.7% of the world's population. While countries are increasingly making efforts to reduce poverty and hunger by pursuing sustainable energy and agricultural practices, a third of the food produced around the globe still is wasted and never consumed. Reducing food shortages is vital in this effort and is often addressed by the development of genetically modified produce or chemical additives and inedible coatings, which create additional health and environmental concerns. Herein, a multifunctional bio-nanocomposite comprised largely of egg-derived polymers and cellulose nanomaterials as a conformal coating onto fresh produce that slows down food decay by retarding ripening, dehydration, and microbial invasion is reported. The coating is edible, washable, and made from readily available inexpensive or waste materials, which makes it a promising economic alternative to commercially available fruit coatings and a solution to combat food wastage that is rampant in the world.