Advances in TEER measurements of biological barriers in microphysiological systems.

Biological barriers are multicellular structures that precisely regulate the transport of ions, biomolecules, drugs, cells, and other organisms. Transendothelial/epithelial electrical resistance (TEER) is a label-free method for predicting the properties of biological barriers. Understanding the mechanisms that control TEER significantly enhances our knowledge of the physiopathology of different diseases and aids in the development of new drugs. Measuring TEER values within microphysiological systems called organ-on-a-chip devices that simulate the microenvironment, architecture, and physiology of biological barriers in the body provides valuable insight into the behavior of barriers in response to different drugs and pathogens. These integrated systems should increase the accuracy, reproducibility, sensitivity, resolution, high throughput, speed, cost-effectiveness, and reliable predictability of TEER measurements. Implementing advanced micro and nanoscale manufacturing techniques, surface modification methods, biomaterials, biosensors, electronics, and stem cell biology is necessary for integrating TEER measuring systems with organ-on-chip technology. This review focuses on the applications, advantages, and future perspectives of integrating organ-on-a-chip technology with TEER measurement methods for studying biological barriers. After briefly reviewing the role of TEER in the physiology and pathology of barriers, standard techniques for measuring TEER, including Ohm's law and impedance spectroscopy, and commercially available devices are described. Furthermore, advances in TEER measurement are discussed in multiple barrier-on-a-chip system models representing different organs. Finally, we outline future trends in implementing advanced technologies to design and fabricate nanostructured electrodes, complicated microfluidic chips, and membranes for more advanced and accurate TEER measurements.

Nanoparticles as Powerful Tools for Crossing the Blood-brain Barrier.

The blood-brain barrier (BBB) is considered an important protective barrier in the central nervous system (CNS). The barrier is mainly formed by endothelial cells (ECs) interconnected by various junctions such as tight junctions (TJs), gap junctions, and adherent junctions. They collectively constitute an intensive barrier to the transit of different substances into the brain, selectively permitting small molecules to pass through by passive movement but holding off large ones such as peptides and proteins to cross the brain. Hence some molecules selectively transfer across the BBB by active routes via transcytosis. The BBB also forms a barrier against neurotoxins as well as pathogenic agents. Although various CNS disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) could hamper the integrity of the border. Nevertheless, the BBB acts as a barrier for CNS disorders treatment because it prevents the drugs from reaching their target in the CNS. In recent years, different strategies, including osmotic disruption of BBB or chemical modification of drugs, have been used to transfer the chemotherapeutic agents into brain substances. Nowadays, nanoparticles (NPs) have been used as an effective and non-invasive tool for drug delivery and diagnosis of CNS disorders. In this review, we discuss the structural characteristic of BBB, safe passageways to cross the BBB, and the relation of barrier lesions with different CNS disorders. In the end, we explore the progress in drug delivery, diagnosis, imaging, and treatment of CNS disorders using nanoparticles.

Advanced Regenerative Medicine Strategies for Treatment of Perianal Fistula in Crohn's Disease.

Regenerative medicine is an emerging therapeutic method that aims to reconstruct tissues and organs. This advanced therapeutic approach has demonstrated great potential in addressing the limitations of medical and surgical procedures for treating perineal fistula in patients with Crohn's disease. Recent developments in stem cell technology have led to a massive good manufacturing practices (GMPs) production of various stem cells, including mesenchymal and embryonic cells, along with induction of pluripotent stem cells to repair damaged tissues in the fistula. The recent advances in separation and purification of exosomes, as biologic nanovesicles carrying anti-inflammatory and regenerative agents, have made them powerful tools to treat this inflammatory disease. Further, tremendous advances in nanotechnology, biomaterials, and scaffold fabrication methods enable tissue engineering methods to synthesize tissue-like structures to assist surgical techniques. This review focuses on advanced regenerative-based methods including stem cell therapy, exosome therapy, and tissue engineering used in the treatment of perianal fistula. Relevant in vitro and in vivo studies and the latest innovations in implementation of regenerative medicine for this disease are also separately reviewed. Additionally, current challenges regarding implementation of g stem cells, exosomes, and tissue engineering methods for bridging the gaps between laboratory findings and clinic application will be discussed.