Development and non-invasive monitoring of tissue-engineered cardiovascular implants

Cardiovascular diseases (CVD) are among the leading causes of death globally, requiring advancements in treatment options. Synthetic vascular grafts and mechanical heart valves have limitations such as thrombosis and the need for repeated surgeries. Tissue-engineered vascular grafts (TEVGs) and heart valves (TEHVs) offer promising alternatives due to their remodeling capabilities and potential to integrate with host tissues. However, challenges remain in ensuring mechanical strength, rapid extracellular matrix (ECM) maturation, and real-time monitoring. Additionally, effective implant life cycle management and long-term follow-up are critical for clinical success. Our research aims to accelerate the development of TEVGs and TEHVs through advanced bioreactor conditioning and 7T MRI monitoring, bringing them closer to clinical application.The first study aimed to enhance the production of TEVGs by significantly shortening the bioreactor conditioning time, which normally takes several weeks. A biodegradable polylactic-co-glycolic acid (PLGA) scaffold, combined with a copolymer-reinforced fibrin gel, was used as a cell carrier. By utilizing the combination of textile, biodegradable fiber, and hydrogel matrix, the conditioning time was reduced to just 4 days, while achieving substantial extracellular matrix (ECM) maturation and mechanical strength. Mechanical testing showed the TEVG’s burst pressure (617±85 mm Hg) and tensile strength exceeded that of native arteries. Additionally, the incorporation of MRI contrast agents into the scaffold allowed for non-invasive in vitro monitoring of scaffold degradation using 7T MRI, providing valuable insights into the remodeling process. The second study focused on the development of a pneumatically driven multimodal bioreactor optimized for MRI and ultrasound imaging for tissue-engineered heart valves (TEHVs). A custom-built bioreactor, designed to operate dynamically within a 72 mm bore of a 7T MRI coil, enabled the real-time monitoring of TEHV functionality without causing MRI interference. TEHVs were constructed using a polyethylene terephthalate (PET) scaffold and human arterial cells, conditioned under physiological conditions. The bioreactor system facilitated the production of ECM components, including collagen and smooth muscle actin, while ensuring a monolayer of endothelial cells. MRI motion compensation techniques and ultrasound imaging successfully captured the dynamic movement of the heart valves, further proving the compatibility of this novel system for longitudinal monitoring.In conclusion, these two studies underscore the potential of tissue-engineered cardiovascular implants for future clinical use. By drastically reducing the conditioning time of TEVGs and enabling dynamic real-time imaging of TEHVs, we have moved closer to developing implants that are not only functional and durable but also capable of being non-invasively monitored during their development and post-implantation phases. These advancements represent a significant step toward creating cardiovascular implants that can be efficiently translated to clinical practice, improving patient outcomes and reducing the need for repeated interventions.