Next-gen heart valve regenerates into heart-like tissue

Posted By : Enaie Azambuja
Next-gen heart valve regenerates into heart-like tissue

A team lead by Kevin Kit Parker, Ph.D. at Harvard University's Wyss Institute for Biologically Inspired Engineering recently developed a nanofibre fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofibre network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM).

To achieve this, the team used the Parker lab's proprietary rotary jet spinning technology - in which a rotating nozzle extrudes an ECM solution into nanofibres that wrap themselves around heart valve-shaped mandrels.

"Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes - much faster than possible for other regenerative prostheses," said Parker.

To further develop and test the clinical potential of JetValves, Parker's team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute.

As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves.

In Hoerstrup's approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an "off-the-shelf" human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue.

"In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal's heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth".

"While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve's much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimising the number of pediatric re-operations," said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth.

The team is also working towards a GMP-grade version of their customisable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

Hoerstrup is Chair and Director of the University of Zurich's Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team's goal is to provide customised, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.


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