Nowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50–100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.

The existence of active crosstalk between cells in a paracrine and juxtacrine manner dictates specific activity under physiological and pathological conditions. Upon juxtacrine interaction between the cells, various types of signaling molecules and organelles are regularly transmitted in response to changes in the microenvironment. To date, it has been well-established that numerous parallel cellular mechanisms participate in the mitochondrial transfer to modulate metabolic needs in the target cells. Since the conception of stem cells activity in the restoration of tissues’ function, it has been elucidated that these cells possess a unique capacity to deliver the mitochondrial package to the juxtaposed cells. The existence of mitochondrial donation potentiates the capacity of modulation in the distinct cells to achieve better therapeutic effects. This review article aims to scrutinize the current knowledge regarding the stem cell’s mitochondrial transfer capacity and their regenerative potential.

The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions.

Advances in microfabrication and biomaterials have enabled the development of microfluidic chips for studying tissue and organ models. While these platforms have been developed primarily for modeling human diseases, they are also used to uncover cellular and molecular mechanisms through in vitro studies, especially in the neurovascular system, where physiological mechanisms and three-dimensional (3D) architecture are difficult to reconstruct via conventional assays. An extracellular matrix (ECM) model with a stable structure possessing the ability to mimic the natural extracellular environment of the cell efficiently is useful for tissue engineering applications. Conventionally used techniques for this purpose, for example, Matrigels, have drawbacks of owning complex fabrication procedures, in some cases not efficient enough in terms of functionality and expenses. Here, we proposed a fabrication protocol for a GelMA hydrogel, which has shown structural stability and the ability to imitate the natural environment of the cell accurately, inside a microfluidic chip utilizing co-culturing of two human cell lines. The chemical composition of the synthesized GelMA was identified by Fourier transform infrared spectrophotometry (FTIR), its surface morphology was observed by field emission electron microscopy (FESEM), and the structural properties were analyzed by atomic force microscopy (AFM). The swelling behavior of the hydrogel in the microfluidic chip was imaged, and its porosity was examined for 72 h by tracking cell localization using immunofluorescence. GelMA exhibited the desired biomechanical properties, and the viability of cells in both platforms was more than 80% for seven days. Furthermore, GelMA was a viable platform for 3D cell culture studies and was structurally stable over long periods, even when prepared by photopolymerization in a microfluidic platform. This work demonstrated a viable strategy to conduct co-culturing experiments as well as modeling invasion and migration events. This microfluidic assay may have application in drug delivery and dosage optimization studies.