Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery

Zeeshan H Syedain, Matthew T. Lahti, Sandra L. Johnson, Paul S. Robinson, George R. Ruth, Richard W Bianco, Robert T Tranquillo

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We have previously demonstrated the feasibility of fabricating a fibrin-based tissue-engineered heart valve (TEHV) using neonatal human dermal fibroblasts (nhDF), including leaflets with structural and mechanical anisotropy similar to native leaflets. The aim here was to evaluate the performance of this TEHV in a pilot study using the sheep model. Bi-leaflet TEHV were conditioned in a cyclic stretching bioreactor, then implanted within a polymeric sleeve interpositionally into the pulmonary artery of four sheep, with the pulmonary valve either left intact or rendered incompetent. Heparin and immunosuppression were administered for the duration. Echocardiography was performed at implantation and at 4 and 8 weeks. Explants were examined histologically, biochemically, and mechanically. In all sheep, echocardiography at implantation showed coapting leaflets, with minimal valve regurgitation and no turbulence. Orifice area and pressure gradients at systole approached the native pulmonary valve values. Echocardiography at 4 weeks revealed both leaflets functional with moderate regurgitation and turbulence in three sheep; in one sheep, only one leaflet was evident. Explanted leaflets had thickness and tensile properties comparable to the implanted leaflets. There was extensive endothelialization of the root lumenal surface. In the two sheep continued to 8 weeks, only one shortened leaflet remained in both cases. Immunocytochemistry indicated this was due to sustained tissue contraction caused by the nhDF and not by the invading host cells, which included a subpopulation consistent with bone marrow-derived cells. Short-term success was thus achieved in terms of excellent valve function at implantation and some valve function for at least 4 weeks; however, an apparent progressive tissue contraction needs to be resolved for long-term success.

Original languageEnglish (US)
Pages (from-to)101-112
Number of pages12
JournalCardiovascular Engineering and Technology
Volume2
Issue number2
DOIs
StatePublished - Jun 1 2011

Fingerprint

Heart Valves
Fibroblasts
Pulmonary Artery
Sheep
Echocardiography
Tissue
Pulmonary Valve
Turbulence
Skin
Orifices
Bioreactors
Pressure gradient
Tensile properties
Systole
Anisotropy
Stretching
Fibrin
Bone
Bone Marrow Cells
Immunosuppression

Keywords

  • Fibrin
  • Fibroblast
  • Heart valve
  • Ovine
  • Tissue-engineering

Cite this

Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery. / Syedain, Zeeshan H; Lahti, Matthew T.; Johnson, Sandra L.; Robinson, Paul S.; Ruth, George R.; Bianco, Richard W; Tranquillo, Robert T.

In: Cardiovascular Engineering and Technology, Vol. 2, No. 2, 01.06.2011, p. 101-112.

Research output: Contribution to journalArticle

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