A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties.
Small-diameter synthetic vascular graft materials fail to match the patency of human tissue conduits used in vascular bypass surgery. The foreign surface retards endothelialization and is highly thrombogenic, while the mismatch in mechanical properties induces intimal hyperplasia. Using recombinant human tropoelastin, we have developed a synthetic vascular conduit for small-diameter applications. We show that tropoelastin enhances endothelial cell attachment (threefold vs. control) and proliferation by 54.7 ± 1.1% (3 days vs. control). Tropoelastin, when presented as a monomer and when cross-linked into synthetic elastin for biomaterials applications, had low thrombogenicity. Activation of the intrinsic pathway of coagulation, measured by plasma clotting time, was reduced for tropoelastin (60.4 ± 8.2% vs. control). Platelet attachment was also reduced compared to collagen. Reductions in platelet interactions were mirrored on cross-linked synthetic elastin scaffolds. Tropoelastin was subsequently incorporated into a synthetic elastin/polycaprolactone conduit with mechanical properties optimized to mimic the human internal mammary artery, including permeability, compliance, elastic modulus and burst pressure. Further, this multilayered conduit presented a synthetic elastin internal lamina to circulating blood and demonstrated suturability and mechanical durability in a small scale rabbit carotid interposition model.
Wise
Steven G
SG
Heart Research Institute, Newtown, NSW, Australia.
Byrom
Michael J
MJ
Waterhouse
Anna
A
Bannon
Paul G
PG
Weiss
Anthony S
AS
Ng
Martin K C
MK
D000328:Adult; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002450:Cell Communication / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D004549:Elastin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D055595:Mechanical Phenomena / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D010865:Pilot Projects; D010973:Platelet Adhesiveness / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology*; D058105:Polymerization / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013718:Tensile Strength / Q000187:drug effects; D023822:Tissue Engineering
D001672:Biocompatible Materials; D011091:Polyesters; D011994:Recombinant Proteins; C016240:polycaprolactone; D004549:Elastin