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

Jolanda Kluin, Hanna Talacua, Anthal I. P. M. Smits, Maximilian Y. Emmert, Marieke C. P. Brugmans, Emanuela S. Fioretta, Petra E. Dijkman, Serge H. M. Söntjens, Renée Duijvelshoff, Sylvia Dekker, Marloes W. J. T. Janssen-van den Broek, Valentina Lintas, Aryan Vink, Simon P. Hoerstrup, Henk M. Janssen, Patricia Y. W. Dankers, Frank P. T. Baaijens, Carlijn V. C. Bouten

Research output: Contribution to journalArticleAcademicpeer-review

217 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)101-117
JournalBiomaterials
Volume125
DOIs
Publication statusPublished - 2017

Cite this