Functional living trileaflet heart valves grown in vitro

Simon P. Hoerstrup, Ralf Sodian, Sabine Daebritz, Jun Wang, Emile A. Bacha, David P. Martin, Adrian M. Moran, Kristine J. Guleserian, Jason S. Sperling, Sunjay Kaushal, Joseph P. Vacanti, Frederick J. Schoen, John E. Mayer

Research output: Contribution to journalArticle

461 Citations (Scopus)

Abstract

Background - Previous tissue engineering approaches to create heart valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. Methods and Results - Trileaflet heart valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosis, thrombus, or aneurysm up to 20 weeks. Histology (16 and 20 weeks) showed uniform layered cuspal tissue with endothelium. Environmental scanning electron microscopy revealed a confluent smooth valvular surface. Mechanical properties were comparable to those of native tissue at 20 weeks. Complete degradation of the polymers occurred by 8 weeks. Extracellular matrix content (collagen, glycosaminoglycans, and elastin) and DNA content increased to levels of native tissue and higher at 20 weeks. Conclusions - This study demonstrates in vitro generation of implantable complete living heart valves based on a biomimetic flow culture system. These autologous tissue-engineered valves functioned up to 5 months and resembled normal heart valves in microstructure, mechanical properties, and extracellular matrix formation.

Original languageEnglish (US)
JournalCirculation
Volume102
Issue number19
StatePublished - Nov 7 2000

Fingerprint

Heart Valves
Biomimetics
Extracellular Matrix
Polymers
Myofibroblasts
Elastin
Tissue Engineering
Glycosaminoglycans
Cardiopulmonary Bypass
Electron Scanning Microscopy
Endothelium
Aneurysm
Echocardiography
In Vitro Techniques
Sheep
Histology
Pathologic Constriction
Thrombosis
Collagen
Endothelial Cells

Keywords

  • Cells
  • Prosthesis
  • Tissue
  • Valves

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hoerstrup, S. P., Sodian, R., Daebritz, S., Wang, J., Bacha, E. A., Martin, D. P., ... Mayer, J. E. (2000). Functional living trileaflet heart valves grown in vitro. Circulation, 102(19).

Functional living trileaflet heart valves grown in vitro. / Hoerstrup, Simon P.; Sodian, Ralf; Daebritz, Sabine; Wang, Jun; Bacha, Emile A.; Martin, David P.; Moran, Adrian M.; Guleserian, Kristine J.; Sperling, Jason S.; Kaushal, Sunjay; Vacanti, Joseph P.; Schoen, Frederick J.; Mayer, John E.

In: Circulation, Vol. 102, No. 19, 07.11.2000.

Research output: Contribution to journalArticle

Hoerstrup, SP, Sodian, R, Daebritz, S, Wang, J, Bacha, EA, Martin, DP, Moran, AM, Guleserian, KJ, Sperling, JS, Kaushal, S, Vacanti, JP, Schoen, FJ & Mayer, JE 2000, 'Functional living trileaflet heart valves grown in vitro', Circulation, vol. 102, no. 19.
Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP et al. Functional living trileaflet heart valves grown in vitro. Circulation. 2000 Nov 7;102(19).
Hoerstrup, Simon P. ; Sodian, Ralf ; Daebritz, Sabine ; Wang, Jun ; Bacha, Emile A. ; Martin, David P. ; Moran, Adrian M. ; Guleserian, Kristine J. ; Sperling, Jason S. ; Kaushal, Sunjay ; Vacanti, Joseph P. ; Schoen, Frederick J. ; Mayer, John E. / Functional living trileaflet heart valves grown in vitro. In: Circulation. 2000 ; Vol. 102, No. 19.
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AU - Sodian, Ralf

AU - Daebritz, Sabine

AU - Wang, Jun

AU - Bacha, Emile A.

AU - Martin, David P.

AU - Moran, Adrian M.

AU - Guleserian, Kristine J.

AU - Sperling, Jason S.

AU - Kaushal, Sunjay

AU - Vacanti, Joseph P.

AU - Schoen, Frederick J.

AU - Mayer, John E.

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N2 - Background - Previous tissue engineering approaches to create heart valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. Methods and Results - Trileaflet heart valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosis, thrombus, or aneurysm up to 20 weeks. Histology (16 and 20 weeks) showed uniform layered cuspal tissue with endothelium. Environmental scanning electron microscopy revealed a confluent smooth valvular surface. Mechanical properties were comparable to those of native tissue at 20 weeks. Complete degradation of the polymers occurred by 8 weeks. Extracellular matrix content (collagen, glycosaminoglycans, and elastin) and DNA content increased to levels of native tissue and higher at 20 weeks. Conclusions - This study demonstrates in vitro generation of implantable complete living heart valves based on a biomimetic flow culture system. These autologous tissue-engineered valves functioned up to 5 months and resembled normal heart valves in microstructure, mechanical properties, and extracellular matrix formation.

AB - Background - Previous tissue engineering approaches to create heart valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. Methods and Results - Trileaflet heart valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosis, thrombus, or aneurysm up to 20 weeks. Histology (16 and 20 weeks) showed uniform layered cuspal tissue with endothelium. Environmental scanning electron microscopy revealed a confluent smooth valvular surface. Mechanical properties were comparable to those of native tissue at 20 weeks. Complete degradation of the polymers occurred by 8 weeks. Extracellular matrix content (collagen, glycosaminoglycans, and elastin) and DNA content increased to levels of native tissue and higher at 20 weeks. Conclusions - This study demonstrates in vitro generation of implantable complete living heart valves based on a biomimetic flow culture system. These autologous tissue-engineered valves functioned up to 5 months and resembled normal heart valves in microstructure, mechanical properties, and extracellular matrix formation.

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