Fast-degrading elastomer enables rapid remodeling of a cell-free synthetic graft into a neoartery

Nat Med. 2012 Jul;18(7):1148-53. doi: 10.1038/nm.2821.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Aorta / physiopathology
  • Arteries / drug effects*
  • Arteries / pathology
  • Arteries / physiopathology
  • Arteries / ultrastructure
  • Blood Vessel Prosthesis Implantation
  • Blood Vessel Prosthesis*
  • Cell-Free System
  • Decanoates / pharmacology*
  • Elastomers / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Glycerol / analogs & derivatives*
  • Glycerol / pharmacology
  • Humans
  • Male
  • Microscopy, Electron, Scanning
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Platelet Adhesiveness / drug effects
  • Polymers / pharmacology*
  • Porosity / drug effects
  • Rats
  • Rats, Inbred Lew
  • Staining and Labeling
  • Tissue Engineering / methods*
  • Vascular Patency / drug effects

Substances

  • Decanoates
  • Elastomers
  • Polymers
  • poly(glycerol-sebacate)
  • Glycerol