title: Tissue-engineered small-caliber vascular graft based on a novel biodegradable composite fibrin-polylactide scaffold.
abstract: Small-caliber vascular grafts (< or =5 mm) constructed from synthetic materials for coronary bypass or peripheral vascular repair below the knee have poor patency rates, while autologous vessels may not be available for harvesting. The present study aimed to create a completely autologous small-caliber vascular graft by utilizing a bioabsorbable, macroporous poly(L/D)lactide 96/4 [P(L/D)LA 96/4] mesh as a support scaffold system combined with an autologous fibrin cell carrier material. A novel molding device was used to integrate a P(L/D)LA 96/4 mesh in the wall of a fibrin-based vascular graft, which was seeded with arterial smooth muscle cells (SMCs)/fibroblasts and subsequently lined with endothelial cells. The mold was connected to a bioreactor circuit for dynamic mechanical conditioning of the graft over a 21-day period. Graft cell phenotype, proliferation, extracellular matrix (ECM) content, and mechanical strength were analyzed. alpha-SMA-positive SMCs and fibroblasts deposited ECM proteins into the graft wall, with a significant increase in both cell number and collagen content over 21 days. A luminal endothelial cell lining was evidenced by vWf staining, while the grafts exhibited supraphysiological burst pressure (>460 mmHg) after dynamic cultivation. The results of our study demonstrated the successful production of an autologous, biodegradable small-caliber vascular graft in vitro, with remodeling capabilities and supraphysiological mechanical properties after 21 days in culture. The approach may be suitable for a variety of clinical applications, including coronary artery and peripheral artery bypass procedures.
authors.affiliation: 1 Department of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, Aachen University , Aachen, Germany .
authors.forename: Beate
authors.initials: B
authors.lastname: Tschoeke
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Flanagan
authors.forename: Sabine
authors.initials: S
authors.lastname: Koch
authors.forename: Marvi Sri
authors.initials: MS
authors.lastname: Harwoko
authors.forename: Thorsten
authors.initials: T
authors.lastname: Deichmann
authors.forename: Ville
authors.initials: V
authors.lastname: Ellå
authors.forename: Jörg S
authors.initials: JS
authors.lastname: Sachweh
authors.forename: Minna
authors.initials: M
authors.lastname: Kellomåki
authors.forename: Thomas
authors.initials: T
authors.lastname: Gries
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz-Rode
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001681:Biological Assay; D001696:Biomechanical Phenomena / Q000187:drug effects; D019149:Bioreactors; D001807:Blood Vessel Prosthesis; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005337:Fibrin / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D011091:Polyesters / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D012756:Sheep; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C033616:poly(lactide); D005337:Fibrin; D006909:Hydroxyproline