Tissue Engineering / in vitro human cell-based blood-brain barrier models
Organ Chip Devices are biomimetic microsystems lined with living cells that replicate key functional and microenvironmental features of whole organs, including tissue-tissue interfaces, mechanical forces, fluid flow, and relevant chemical gradients.
Mustafaoglu Lab is dedicated to developing novel microfluidic systems that accurately replicate the blood-brain barrier (BBB) under physiological conditions in both healthy and diseased states. Our research encompasses various aspects, including establishing new protocols for differentiating stem cells into neurons and brain endothelial cells. Additionally, we design and fabricate unique microfluidic devices featuring channels capable of exerting shear and tensile stresses on cells to simulate physiological vascular movements within the brain. Our in vitro BBB models successfully replicate the permeability barrier, the physiologically relevant expression of tight junction proteins, and the functionality of multiple drug transporters. Importantly, these physiologically relevant human cell-based models enable the development of novel drug delivery approaches for the treatment of brain diseases. To enhance our models, we are employing state-of-the-art engineering approaches to incorporate sensors into our microfluidic models. This integration allows us to develop novel, human-based, in vitro models of the BBB that faithfully mimic key features observed in vivo and monitor simultaneous changes in disease development. These advancements could be utilized for drug screening purposes as well.
Drug delivery refers to processes, formulations, methods, and systems to safely distribute a nanoparticle-based pharmaceutical product in the body for as long as it is needed to achieve the desired therapeutic effect.
Our group focuses on two main areas: developing advanced drug delivery systems and innovative nanoparticle targeting strategies. Our primary aim is to improve the treatment of central nervous system (CNS) diseases and cancer, ultimately leading to better patient outcomes. To achieve this, we combine our expertise in state-of-the-art wet lab techniques and physiologically relevant functional organ models with collaborations for computational approaches. Within our research, a major emphasis lies in designing nano-shuttle systems capable of crossing the blood-brain barrier (BBB). This presents a significant challenge in the field of drug delivery because the BBB, while evolutionarily advantageous, poses obstacles for delivering drugs to the brain. In fact, over 99% of drugs cannot pass through the BBB. In our lab, we address this problem by developing novel nano-shuttle systems decorated with functional moieties to target proteins on brain endothelial cells. These systems enable transcytosis, facilitating the delivery of drugs to the brain for the treatment of CNS disorders.
