Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring

Zeeshan H Syedain, Lee A Meier, Jason W. Bjork, Ann Lee, Robert T Tranquillo

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Tissue-engineered arteries based on entrapment of human dermal fibroblasts in fibrin gel yield completely biological vascular grafts that possess circumferential alignment characteristic of native arteries and essential to their mechanical properties. A bioreactor was developed to condition six grafts in the same culture medium while being subjected to similar cyclic distension and transmural flow resulting from pulsed flow distributed among the graft lumens via a manifold. The lumenal pressure and circumferential stretch were noninvasively monitored and used to calculate stiffness in the range of 80-120 mmHg and then to successfully predict graft burst strength. The length of the graft was incrementally shortened during bioreactor culture to maintain circumferential alignment and achieve mechanical anisotropy comparable to native arteries. After 7-9 weeks of bioreactor culture, the fibrin-based grafts were extensively remodeled by the fibroblasts into circumferentially-aligned tubes of collagen and other extracellular matrix with burst pressures in the range of 1400-1600 mmHg and compliance comparable to native arteries. The tissue suture retention force was also suitable for implantation in the rat model and, with poly(lactic acid) sewing rings entrapped at both ends of the graft, also in the ovine model. The strength achieved with a biological scaffold in such a short duration is unprecedented for an engineered artery.

Original languageEnglish (US)
Pages (from-to)714-722
Number of pages9
JournalBiomaterials
Volume32
Issue number3
DOIs
StatePublished - Jan 1 2011

Fingerprint

Pulsatile flow
Bioreactors
Fibroblasts
Fibrin
Grafts
Transplants
Monitoring
Arteries
Tissue
Pressure
Anisotropy
Lactic acid
Collagen
Scaffolds
Sutures
Compliance
Extracellular Matrix
Blood Vessels
Culture Media
Rats

Keywords

  • Bioreactor
  • Cyclic stretching
  • Fibrin
  • Fibroblast
  • Transmural flow
  • Vascular graft

Cite this

Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring. / Syedain, Zeeshan H; Meier, Lee A; Bjork, Jason W.; Lee, Ann; Tranquillo, Robert T.

In: Biomaterials, Vol. 32, No. 3, 01.01.2011, p. 714-722.

Research output: Contribution to journalArticle

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