title: Engineering of living autologous human umbilical cord cell-based septal occluder membranes using composite PGA-P4HB matrices.
abstract: Interventional closure of intracardiac wall defects using occluder devices has evolved as a highly attractive treatment option. However, incomplete and delayed healing reactions often result in a major risk of residual defects, thromboembolism, or device fractures. Biodegradable living tissue engineered occluder membranes (TEOMs) could provide autologous thromboresistant implants with growth and remodeling capacities. PGA-P4HB composite matrices were seeded with human umbilical cord-derived cells or vascular-derived control cells and exposed to static (n = 19) or dynamic (n = 13) conditioning. Harvested TEOMs were integrated into occluder frameworks, exposed to crimping and delivered into pre-formed defects of juvenile porcine hearts. Dynamically conditioned TEOM constructs showed higher collagen formation in histology than static constructs with significantly higher stiffness moduli in uniaxial tensile testing. Grating interferometry revealed substantial but inhomogeneous cone-like degradation of the composite matrices in dynamic conditioning. The crimping and delivery procedures resulted in no significant changes in macroscopy, histo-morphology, cellular viability, DNA or hydroxyproline content, and scanning electron microscopy findings. Here, we present the in vitro fabrication, crimping and experimental delivery of living human umbilical cord-cell derived TEOMs based on composite matrices as a potential future autologous therapy of intracardiac wall defects.
authors: Swiss Center for Regenerative Medicine, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors: Benedikt
authors: B
authors: Weber
authors: Roman
authors: R
authors: Schoenauer
authors: Francesca
authors: F
authors: Papadopulos
authors: Peter
authors: P
authors: Modregger
authors: Silvia
authors: S
authors: Peter
authors: Marco
authors: M
authors: Stampanoni
authors: Arabella
authors: A
authors: Mauri
authors: Edoardo
authors: E
authors: Mazza
authors: Julia
authors: J
authors: Gorelik
authors: Irina
authors: I
authors: Agarkova
authors: Laura
authors: L
authors: Frese
authors: Christian
authors: C
authors: Breymann
authors: Oliver
authors: O
authors: Kretschmar
authors: Simon P
authors: SP
authors: Hoerstrup
mesh_terms: D000818:Animals; D057005:Bioengineering; D001696:Biomechanical Phenomena; D002469:Cell Separation; D048430:Cell Shape; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007368:Interferometry; D008422:Materials Testing; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D055989:Septal Occluder Device; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014022:Tissue Survival; D014470:Umbilical Cord / Q000166:cytology*; D059631:Wharton Jelly / Q000166:cytology
chemical_list: D008567:Membranes, Artificial; D011091:Polyesters; C107955:poly(4-hydroxybutanoate); D011100:Polyglycolic Acid