Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Tubular TPU/SF nanofibers covered with chitosan-based hydrogels as small-diameter vascular grafts with enhanced mechanical properties.

Native grafts such as internal mammary artery and saphenous vein are the main choice for coronary artery bypass graft. However, due to the limitations associated with their availability and rapid failure caused by hyperplasia, small diameter tissue-engineered vascular grafts (TEVGs) with sufficient post-implantation patency are urgently demanded as artificial alternatives. In our previous work, we innovatively fabricated a bilayer vascular graft providing appropriate structural and biological properties using electrospinning and freeze-drying methods. It was proved that the mechanical properties of the proposed graft enhanced in comparison with using either of methods individually. Here, we adopted the same methods and incorporated an anticoagulant internal layer (inner diameter 4 mm), comprised of co-electrospun fibers of silk fibroin (SF) and heparinized thermoplastic polyurethane (TPU), and an external highly porous hydrogel fabricated by freeze-drying method. The electrospun layer exhibited strong mechanical properties including superior elastic modulus (4.92 ± 0.11 MPa), suture retention force (6.73 ± 0.83 N), elongation at break (196 ± 4%), and comparable burst pressure (1140 ± 12 mmHg) while the external hydrogel provided SMCs viability. The heparin was released in a sustain manner over 40 days, and the cytocompatibility and blood compatibility of scaffold were approved using MTT assay and platelet adhesion test. Thus, the proposed graft has a potential to be used as an artificial blood vessel scaffold for later in-vivo transplantation.

Modeling of an Ultrasound System in Targeted Drug Delivery to Abdominal Aortic Aneurysm: A Patient-Specific in Silico Study Based on Ligand-Receptor Binding.

Targeted drug delivery methods have shown a significant impact on enhancing drug delivery efficiency and reducing drug side effects. While various stimuli have been used to promote the drug delivery process, applying ultrasound (US) waves to control drug particles through the human body, noninvasively, has drawn the scientist's attention. However, microcarriers delivery reaches the aneurysmal artery by US waves that exert volumetric forces on blood, and drug carriers, which can therefore affect blood flow patterns and movement pathways of drug carriers, have not yet been studied. In this study, we developed a 3-D patient-specific model of abdominal aortic aneurysm (AAA) to evaluate the effect of US waves in enhancing the drug-containing microbubbles (MBs) adhered on the AAA lumen through ligand-receptor binding. Thus, a focused US (FUS) transducer with a resonance frequency of ~1.1 MHz was added to the geometry. Then, the surface density of MBs (SDM) adhered on the AAA lumen was calculated at peak acoustic pressure of ~1.1, ~2.2, and ~4.3 MPa. Results indicated that increasing the US pressure had a significant impact on improving the MBs adhered to the intended wall, whereby US waves with the maximum pressure of ~4.3 MPa could enhance ~1- [Formula: see text] MBs adhesion ~98% relative to not using the waves. While US waves have the advantage of more SDM adhered to the whole artery wall, they adversely affect the SDM adhered on the critical wall of the abdominal aorta. Furthermore, when the US strength goes up, a reduction occurs in the SDM adhered. This reduction is higher for smaller MBs, which is the mentioned MBs' size and US strength reduced SDM adhesion by about ~50% relative to systemic injection. Therefore, it can be concluded that drug delivery using the US field increases the SDM adhered to the whole AAA wall and decreases the SDM adhered to the critical wall of AAA.