Layer by layer Multiplexing of 3d cardiovascular tissue-based biosensor for Drug Discovery.

Fighting the #1 Killer in the UAE, and world

Cardiovascular Disease (CVD) has emerged in recent decades as the leading cause of mortality around the globe. According to the World Health Organization, over 17 million people died in 2015 due to CVD and associated complications. The UAE has a particular stake in researching ways to cure CVD as UAE residents die of CVD 20 years earlier than the global average—as the youngest population in the world. These alarming statistics are driving a team of researchers at Khalifa University, led by Biomedical Engineer Dr. Vincent Chan, to find an innovative new way to test pre-clinical drug efficacy on patients suffering from CVD.

The process of getting drugs through clinical trials and to market for conditions such as CVD can be very costly and protracted as it deals with a sensitive organ, where gathering data or samples of tissue can be invasive and further complicate the health of patients. By developing sensors for patients at the area being studied, researchers are able to receive valuable data in real time as the drug is interacting in its intended environment. This method to gather data in biomimetics allows researchers to accurately gauge the efficacy of drugs on the cellular level.

“Current pre-clinical testing of new drug leads for CVD hinges on the applications of cell culture and animal models which fail to fully recapitulate the physiology and mechanobiology of the highly organized multicellular architecture found in native blood vessels” said Dr. Chan. “Thus, an innovative yet robust on-line biosensor which simultaneously promotes the physiological functions of human vascular tissues and hosts a series of embedded mechanical transducers will accelerate the pace of identifying potential CVD drug candidates for the treatment of common CVDs like hypertension in a more effective and economical way.”

Two-dimensional (2D) cell culture systems have been in use in clinical research for years and have enabled the research of simple organ models. Monolayer cell cultures were easy to create and were compatible with existing lab infrastructure and equipment. While being convenient, the 2D structures posed serious limitations for researchers when attempting to replicate more structurally advanced tissues where spatiotemporal biochemical gradients were required system parameters.

By reconstructing the three-dimensional (3D) printed tissue into bioprinted functional scaffold, researchers at Khalifa University are unraveling a multitude of applications in the pharmaceutical industry from their research and preliminary findings. “We intend to develop an integrative 3D tissue-based biosensor with multiplexed detection transducers and fully simulated functionality in controlled microenvironment for high throughput drug testing and toxicological studies,” said Dr. Chan. “In order to do this, we need to design innovative biomaterial which simultaneously promotes the maintenance of differentiated functions in human vascular tissues and provides an engineered array of embedded mechanical transducers for the realization of a cell-based biosensor.”

Tissue models that reproduce in vivo conditions as closely as possible are essential to learning about the interaction of drugs on the cellular level as researchers strive to discover new agents and therapies during the drug-development process. Microsystem technology offers new approaches to culturing and analyzing human cells and functional tissue structures with sensors that report accurate and integral data.

Traditionally, medical practitioners prescribe lifestyle changes to patients at risk for CVD, and medicine for those whose symptoms have already manifested. Lifestyle changes are the optimal solution, yielding longer lasting and more pervasive improvements to heart and overall patient health, but are harder to implement and adopt. Alternatively, prescribed drugs have a strong impact on patients not able to pursue or maintain lifestyle changes, with health benefits obtained quickly. Doctors always suggest lifestyle changes to avoid dependency on drugs, and allow the patient to live a healthy and natural lifestyle, but the medicines produced through clinical trials are irreplaceable.

As methods for testing the impact of drugs in clinical trials becomes safer, easier, and faster, the process of moving trial drugs to the market will be expedited, cheaper for consumers, and efficacy of drugs will be improved for maximal health and impact.