Scientists develop series of heart valve replacements to implant host cells into lambs

Combining tissue engineering and regenerative medicine, scientists have fabricated a series of heart valve replacements with the ability to incorporate host cells, enabling them to regenerate and grow over time.

The valves expanded and maintained their function for a year when implanted into growing lambs, suggesting they could address the dire need for a long-term valve replacement for children with congenital heart disorders. These pediatric patients depend on mechanical or prosthetic heart valves for survival, but current devices often calcify over time and cannot grow alongside the child's heart.

As a result, these patients routinely undergo as many as five open heart surgeries to have their valves repeatedly replaced until they reach adulthood. These procedures carry significant risks and healthcare costs, and pediatric patients must continue to take lifelong anticoagulation therapy.

Building on their previous work, Zeeshan Syedain and colleagues manufactured a pediatric valve replacement that adapts to the growing heart and can host layers of cells. Using tissue engineering, the authors based their valve replacement on three tubes of decellularized extracellular matrix, which can become populated with cells after implantation.

The first generation of tri-tube valves increased in diameter over a span of 52 weeks after being implanted into four lambs, but exhibited some blood regurgitation and degraded valve function over time. Syedain et al. then devised a second-generation design that includes an additional tube sleeve, which improved growth dynamics and mitigated blood pressure drops in two lambs in a second group of animals.

Importantly, the valves also showed fewer signs of damaging calcification than clinically used bioprosthetic valves in the lambs. The scientists call for studies with larger cohorts to better assess the long-term potential of both tri-tube valve designs.

Source:
Journal reference:

Syedain, Z. H., et al. (2021) Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb7225.

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