In situ heart valve tissue engineering using a bioresorbable elastomeric implant – From material design to 12 months follow-up in sheep

TLDR

Living heart valves are sought to overcome durability and thromboembolic complications of current prostheses. The study demonstrates a proof‑of‑concept for in situ heart valve tissue engineering using a cell‑free, slow‑degrading elastomeric implant that recruits endogenous cells to regenerate valve tissue. A fibrous scaffold made from a novel supramolecular elastomer was fabricated to allow endogenous cells to infiltrate and produce matrix. In sheep, the implant functioned for 12 months and was progressively replaced by collagen and elastic matrix as the polymer resorbed, demonstrating the feasibility of a synthetic graft for endogenous heart valve replacement.

Abstract

The creation of a living heart valve is a much-wanted alternative for current valve prostheses that suffer from limited durability and thromboembolic complications. Current strategies to create such valves, however, require the use of cells for in vitro culture, or decellularized human- or animal-derived donor tissue for in situ engineering. Here, we propose and demonstrate proof-of-concept of in situ heart valve tissue engineering using a synthetic approach, in which a cell-free, slow degrading elastomeric valvular implant is populated by endogenous cells to form new valvular tissue inside the heart. We designed a fibrous valvular scaffold, fabricated from a novel supramolecular elastomer, that enables endogenous cells to enter and produce matrix. Orthotopic implantations as pulmonary valve in sheep demonstrated sustained functionality up to 12 months, while the implant was gradually replaced by a layered collagen and elastic matrix in pace with cell-driven polymer resorption. Our results offer new perspectives for endogenous heart valve replacement starting from a readily-available synthetic graft that is compatible with surgical and transcatheter implantation procedures.