In Situ Cardiovascular Tissue Engineering using Degradable Polymeric Scaffolds: Scaffold Optimization and Long-term In-vivo Follow-up
Jolanda Kluin1, Anthal Smits2, Hanna Talacua1, Emanuela Fioretta3, Max Emmert3, Serge Söntjens4, Henk Janssen4, Simon Hoerstrup3, Patricia Dankers2, Frank Baaijens2, Carlijn Bouten2.
1Academic Medical Center, Amsterdam, Netherlands, 2Eindhoven University of Technology, Eindhoven, Netherlands, 3University of Zürich, Zürich, Switzerland, 4SyMO-CHEM, Eindhoven, Netherlands.
BACKGROUND: We investigate and design in situ heart valve tissue engineering technologies using cell-free biodegradable synthetic scaffolds as an approach to create living valves inside the human heart. While this would constitute a simple procedure, starting from the implantation of a biomaterial device', it requires the development of advanced materials and a detailed understanding of the interactions between endogenous cells, scaffold, and tissue formation under hemodynamic conditions. The challenge is to develop instructive scaffolds that i) are capable of harnessing the natural host response; ii) guide selective host cell population, and iii) provide necessary biochemical and biophysical cues for a stable cellular phenotype and an organized load-bearing extracellular matrix.
METHODS: We used electrospun, highly porous, microfiber scaffolds made of supramolecular materials that can be functionalized with bioactives to elicit specific responses of host cells, typically recruited from the blood stream. Biomimetic in vitro models and computational analyses were used in direct comparison with in vivo small-animal experiments (orthotopic aorta implantations) to optimize scaffold biochemical, biophysical ((an)isotropy, fiber diameter, scaffold mechanical properties), and degradation properties. Next, scaffolds were tested as pulmonary valve substitutes.
RESULTS: We optimized scaffold fiber diameter (> 3,5 micrometer), or the release of bioactive moieties (e.g. SDF1alpha), to modulate cell-driven degradation and inflammatory responses under hemodynamic loading to favor the recruitment of beneficial macrophage subpopulations. Small-animal studies demonstrated functional vessel formation during 3-month FU, with improved tissue properties (e.g. faster cell recruitment, elastin formation) following bioactive modification. Orthotopic (12-month FU) and transcatheter (6-month FU) implantations of materials as pulmonary valve in sheep demonstrated sustained mechanical and biological functionality, while the implant was gradually replaced by a layered collagen and elastin matrix in pace with scaffold degradation and endothelialization.
CONCLUSION: These results offer new perspectives for endogenous heart valve replacement starting from readily-available synthetic grafts.
Back to 2018 Program