Fast-degrading elastomer enables rapid remodeling of a cell-free synthetic graft into a neoartery.
Host remodeling is important for the success of medical implants, including vascular substitutes. Synthetic and tissue-engineered grafts have yet to show clinical effectiveness in arteries smaller than 5 mm in diameter. We designed cell-free biodegradable elastomeric grafts that degrade rapidly to yield neoarteries nearly free of foreign materials 3 months after interposition grafting in rat abdominal aorta. This design focuses on enabling rapid host remodeling. Three months after implantation, the neoarteries resembled native arteries in the following aspects: regular, strong and synchronous pulsation; a confluent endothelium and contractile smooth muscle layers; expression of elastin, collagen and glycosaminoglycan; and tough and compliant mechanical properties. Therefore, future studies employing large animal models more representative of human vascular regeneration are warranted before clinical translation. This cell-free approach represents a philosophical shift from the prevailing focus on cells in vascular tissue engineering and may have an impact on regenerative medicine in general.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Wei
W
Wu
Robert A
RA
Allen
Yadong
Y
Wang
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002474:Cell-Free System; D003651:Decanoates / Q000494:pharmacology*; D020724:Elastomers / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010973:Platelet Adhesiveness / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D014654:Vascular Patency / Q000187:drug effects
D003651:Decanoates; D020724:Elastomers; D011108:Polymers; C469892:poly(glycerol-sebacate); D005990:Glycerol