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TEKNOKONVERGENS-Teknologikonvergens - grensesprengende forskning og radikal innovasjon

Automated Production of Tissue-Engineered Vein Grafts

Alternative title: Automatisert Produksjon av Vevskonstruerte Venetransplantater

Awarded: NOK 14.0 mill.

A healthy vein has valves that make sure that blood can flow only in one direction and is efficiently transported back to the heart. Yet, at times, these valves can get leaky. Blood starts to flow backward (reflux) and accumulates legs and feet. This pooling of blood causes a cascade of symptoms ranging from visible vein deformations, to swelling, to skin discoloration and irritation, to painful slow-healing wounds, so-called ulcers. This medical condition is referred to as chronic venous insufficiency (CVI) due to reflux. The most severe forms of CVI alone affect about 2M patients in Europe and the US. Currently, there are no ways to treat CVI. Replacing the damaged valves with an implant to correct the blood flow is challenging since the slow-flowing venous blood easily starts to clot. A theoretical implant must thus provide a blood-compatible surface similar to the tissue of a native vein. So what if one could grow an implant made out of human vein tissue in the lab? Recent advances have demonstrated that human tissues can be grown in the lab. However, the existing methods are limited to rather simple geometries such as tubes or sheets, and can not be translated to growing the complex geometry of a vein with functional valves. In laboratory experiments, ClexBio’s innovative technology VivoSet has shown potential to overcome this limitation. The paste-like VivoSet material can be cast into any mold and provides ideal conditions for growing strong human tissues. In this project, ClexBio will use VivoSet and together with the Swiss research institute CSEM develop the world’s first machine to grow human veins in the lab. The resulting vein implants will be a game-changer for the millions of patients around the globe suffering from CVI. Once implanted, they will become living tissue that grows and renews itself with the patient correcting the blood flow and eliminating the root cause of CVI.

Currently, no treatment options exist to permanently cure severe chronic venous insufficiency (CVI) that affects millions of patients worldwide. While the huge unmet need for CVI treatments has sparked a number of creative attempts to address the disease's underlying cause, venous reflux, these attempts suffer from concerns regarding safety and reproducibility hampering clinical implementation at scale. Recent methods to tissue-engineer mechanically strong grafts have impressively demonstrated the feasibility to grow human tissues in a controlled and commercially scalable way. However, they are limited to simple geometries such as skin (sheets), arteries (tubes), or bone (blocks) that limit their applicability to tissues with complex geometry such as veins with functional valves. ClexBio's innovative and proprietary VivoSet technology has the promise to overcome this limitation. VivoSet is freely moldable and has demonstrated the capacity to form thick, mechanically strong tissues in complex geometries. To harness the potential of the VivoSet technology, the laboratory proof-of-concept method needs to be translated into a scalable process. The objective of SuperVene is to develop an automated manufacturing process to engineer functional human vein grafts in a closed system. The project will develop an innovative tissue reactor unit connected to a pulsed perfusion and environmental control system to culture complex-shaped vein tissues in a closed, automated system. Next-generation VivoSet formulations adapted for vein engineering will be established and produced using newly developed high-throughput microfluidic devices. Lastly, engineered vein grafts will be validated in vitro. This project will develop new knowledge, processes, and technology to produce tissue-engineered vein grafts with functional valves. This forms the foundation for commercial manufacturing in a regulation-compliant and cost-efficient manner and enables the translation to clinical use.

Funding scheme:

TEKNOKONVERGENS-Teknologikonvergens - grensesprengende forskning og radikal innovasjon