Clinical translation of a restorative heart valve: progress & challenges

Introduction: Despite significant research efforts from academic centers, there are only few examples of cardiovascular tissue engineering applications that made it to clinical stage. The technological challenges of persuading living cells to produce functional valves or vessels are significant, and the additional challenge of translating an early proof of feasibility into a robust and consistent process and product should not be underestimated. The most significant challenge however is the regulatory approval process, and the quality assurance measures that need to be put in place to ensure consistent quality and regulatory compliance. Especially for in vitro tissue engineering approaches, where living cells are manipulated in bioreactors for extended periods of time, this results in complex and costly production processes, which makes commercial translation of these approaches less attractive.

Methods : To overcome these challenges, we propose a different approach for cardiovascular treatment, called Endogenous Tissue Restoration (ETR). Using electrospinning and supramolecular chemistry, we have developed off-the-shelf polymeric devices that allow ETR. The goal of ETR is to enable the body’s natural healing process to pervade the devices with components of native tissue, including collagen, endothelial lining and capillary blood vessels, which normally develop and organize into natural functioning tissue. The polymeric devices are structured to be absorbed over time, to leave patients with new, healthy tissues.

Result: After successfully conducting long term preclinical trials, we were able to bring our approach to clinical application in a feasibility trial using a large diameter graft in a Fontan procedure in 5 single-ventricle pediatric patients ( , NCT02377674). Building on that, we developed a pulmonary valved conduit through further long term preclinical testing. Currently, we are running a world-first clinical feasibility trial, in which 12 pediatric patients received a new pulmonary valved conduit designed to allow ETR ( , NCT02700100).

Conclusions: We report on reaching clinical stage with a restorative pulmonary valved conduit that is designed to allow ETR. The product qualifies as a medical device, thus reducing the complexity and costs associated with clinical and commercial translation of conventional tissue engineered products. Continued success could represent a paradigm shift in the approach to cardiovascular regeneration strategies.