Author + information
- Received June 12, 2009
- Revision received April 8, 2010
- Accepted April 13, 2010
- Published online August 3, 2010.
- Dörthe Schmidt, MD, PhD⁎,†,‡,
- Petra E. Dijkman, MSc§,
- Anita Driessen-Mol, PhD§,
- Rene Stenger, BSc‡,
- Christine Mariani, MSc∥,
- Arja Puolakka, MSc∥,
- Marja Rissanen, LicTech∥,
- Thorsten Deichmann, DiplIng¶,
- Bernhard Odermatt, MD#,
- Benedikt Weber, MD⁎,†,‡,
- Maximilian Y. Emmert, MD⁎,†,‡,
- Gregor Zund, MD‡,
- Frank P.T. Baaijens, PhD§ and
- Simon P. Hoerstrup, MD, PhD⁎,†,‡,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Simon P. Hoerstrup, Clinic for Cardiovascular Surgery, Department of Surgical Research, University Hospital Zurich, Raemistrasse 100, Zurich CH 8091, Switzerland
Objectives The aim of this study was to demonstrate the feasibility of combining the novel heart valve replacement technologies of: 1) tissue engineering; and 2) minimally-invasive implantation based on autologous cells and composite self-expandable biodegradable biomaterials.
Background Minimally-invasive valve replacement procedures are rapidly evolving as alternative treatment option for patients with valvular heart disease. However, currently used valve substitutes are bioprosthetic and as such have limited durability. To overcome this limitation, tissue engineering technologies provide living autologous valve replacements with regeneration and growth potential.
Methods Trileaflet heart valves fabricated from biodegradable synthetic scaffolds, integrated in self-expanding stents and seeded with autologous vascular or stem cells (bone marrow and peripheral blood), were generated in vitro using dynamic bioreactors. Subsequently, the tissue engineered heart valves (TEHV) were minimally-invasively implanted as pulmonary valve replacements in sheep. In vivo functionality was assessed by echocardiography and angiography up to 8 weeks. The tissue composition of explanted TEHV and corresponding control valves was analyzed.
Results The transapical implantations were successful in all animals. The TEHV demonstrated in vivo functionality with mobile but thickened leaflets. Histology revealed layered neotissues with endothelialized surfaces. Quantitative extracellular matrix analysis at 8 weeks showed higher values for deoxyribonucleic acid, collagen, and glycosaminoglycans compared to native valves. Mechanical profiles demonstrated sufficient tissue strength, but less pliability independent of the cell source.
Conclusions This study demonstrates the principal feasibility of merging tissue engineering and minimally-invasive valve replacement technologies. Using adult stem cells is successful, enabling minimally-invasive cell harvest. Thus, this new technology may enable a valid alternative to current bioprosthetic devices.
This work was supported by the Center for Integrative Human Physiology, University Zurich; the Dutch Program for Tissue Engineering; Xeltis Inc.Switzerland; and in part by the European Union–funded project “Intelligent Biomaterial Systems for Cardiovascular Tissue Repair” (BioSys; STRP 013633). Drs. Schmidt, Dijkman, and Driessen-Mol contributed equally to this work.
- Received June 12, 2009.
- Revision received April 8, 2010.
- Accepted April 13, 2010.
- American College of Cardiology Foundation