Allogeneic human tissue-engineered blood vessel

J Vasc Surg. 2012 Mar;55(3):790-8. doi: 10.1016/j.jvs.2011.07.098. Epub 2011 Nov 4.

Abstract

Background: Arterial bypass graft implantation remains the primary therapy for patients with advanced cardiovascular disease; however, there is no available synthetic small-diameter vascular graft.

Methods: Tissue-engineered vessels were grown from human smooth muscle cells that were seeded on a biodegradable scaffold using a biomimetic perfusion system. The human tissue-engineered vessels (hTEV) were decellularized by a two-step process using a combination of detergents and hypertonic solutions. The mechanical characteristics were assessed by suture retention strength and burst pressure. The decellularized hTEV were implanted as aortic interpositional grafts in nude rats to evaluate in vivo performance as an arterial graft over a 6-week period.

Results: The human tissue-engineered structure formed a vessel composed of smooth muscle cells and the extracellular matrix proteins, including collagen. After decellularization, the collagen matrix remained intact while the cellular components were removed. The mechanical strength of the hTEV after decellularization was similar to human vein in vitro, with a burst pressure of 1,567 ± 384 mm Hg (n = 3) versus 1,680 ± 307 mm Hg for human saphenous vein. The hTEVs had a high patency rate (four of five grafts) without evidence of rupture or aneurysm over a 6-week period as an aortic interpositional graft in a nude rat model. Histologic analysis showed a thin neointima with a confluent endothelium and a subendothelial layer of smooth muscle cells on the explanted tissue-engineered vessels. Transmission electron microscopy on the explanted tissue demonstrated elastin formation in the neointima and intact residual collagen fibers from the tissue-engineered vessel.

Conclusions: The hTEV had a high patency rate and remained mechanically stable as an aortic interpositional graft in a nude rat. The vessel supported the growth of a neointima with endothelial cells and smooth muscle cells. The host remodeling suggested the engineered matrix had a positive effect to create a regenerated vascular graft.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Abdominal / diagnostic imaging
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / surgery*
  • Biomechanical Phenomena
  • Blood Vessel Prosthesis Implantation / instrumentation*
  • Blood Vessel Prosthesis*
  • Cells, Cultured
  • Detergents / chemistry
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Hydrostatic Pressure
  • Hypertonic Solutions / chemistry
  • Microscopy, Electron, Transmission
  • Muscle, Smooth, Vascular / diagnostic imaging
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / transplantation*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / transplantation*
  • Myocytes, Smooth Muscle / ultrastructure
  • Prosthesis Failure
  • Rats
  • Rats, Nude
  • Stress, Mechanical
  • Suture Techniques
  • Time Factors
  • Tissue Engineering* / methods
  • Ultrasonography
  • Vascular Patency
  • X-Ray Microtomography

Substances

  • Detergents
  • Extracellular Matrix Proteins
  • Hypertonic Solutions