Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

Current mechanical conditioning approaches for heart valve tissue engineering concentrate on mimicking the opening and closing behavior of the leaflets, either or not in combination with tissue straining. This study describes a novel approach by mimicking only the diastolic phase of the cardiac cycle, resulting in tissue straining. A novel, yet simplified, bioreactor system was developed for this purpose by applying a dynamic pressure difference over a closed tissue engineered valve, thereby inducing dynamic strains within the leaflets. Besides the use of dynamic strains, the developing leaflet tissues were exposed to prestrain induced by the use of a stented geometry. To demonstrate the feasibility of this strain-based conditioning approach, human heart valve leaflets were engineered and their mechanial behavior evaluated. The actual dynamic strain magnitude in the leaflets over time was estimated using numerical analyses. Preliminary results showed superior tissue formation and non-linear tissue-like mechanical properties in the strained valves when compared to non-loaded tissue strips. In conclusion, the strain-based conditioning approach, using both prestrain and dynamic strains, offers new possibilities for bioreactor design and optimization of tissue properties towards a tissue-engineered aortic human heart valve replacement.

[1]  Frank P T Baaijens,et al.  Fibrin as a cell carrier in cardiovascular tissue engineering applications. , 2005, Biomaterials.

[2]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[3]  Frank P T Baaijens,et al.  A structural constitutive model for collagenous cardiovascular tissues incorporating the angular fiber distribution. , 2005, Journal of biomechanical engineering.

[4]  Roland Hetzer,et al.  Tissue-engineering bioreactors: a new combined cell-seeding and perfusion system for vascular tissue engineering. , 2002, Tissue engineering.

[5]  P. E. McHugh,et al.  Bioreactors for Cardiovascular Cell and Tissue Growth: A Review , 2003, Annals of Biomedical Engineering.

[6]  F J Schoen,et al.  Functional Living Trileaflet Heart Valves Grown In Vitro , 2000, Circulation.

[7]  Chrysanthi Williams,et al.  Perfusion bioreactor for small diameter tissue-engineered arteries. , 2004, Tissue engineering.

[8]  Bart Meuris,et al.  Design of a new pulsatile bioreactor for tissue engineered aortic heart valve formation. , 2002, Artificial organs.

[9]  T. Yaginuma,et al.  Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-beta 1 and tissue-type plasminogen activator. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[10]  Joseph P Vacanti,et al.  A novel pulsatile, laminar flow bioreactor for the development of tissue-engineered vascular structures. , 2002, Tissue engineering.

[11]  Robert M. Nerem,et al.  Dynamic Mechanical Conditioning of Collagen-Gel Blood Vessel Constructs Induces Remodeling In Vitro , 2000, Annals of Biomedical Engineering.

[12]  R Langer,et al.  Functional arteries grown in vitro. , 1999, Science.

[13]  D. Shepro,et al.  Comparison of the effects of mechanical stimulation on venous and arterial smooth muscle cells in vitro. , 1996, Journal of vascular research.

[14]  A. Ratcliffe,et al.  Fluid shear stress-induced alignment of cultured vascular smooth muscle cells. , 2002, Journal of biomechanical engineering.

[15]  R. Sodian,et al.  Optimal cell source for cardiovascular tissue engineering: venous vs. aortic human myofibroblasts. , 2001, The Thoracic and cardiovascular surgeon.

[16]  Simon P. Hoerstrup,et al.  Cardiovascular tissue engineering: a new laminar flow chamber for in vitro improvement of mechanical tissue properties. , 2000 .

[17]  Christopher J. O’Callaghan,et al.  Mechanical Strain–Induced Extracellular Matrix Production by Human Vascular Smooth Muscle Cells: Role of TGF-&bgr;1 , 2000, Hypertension.

[18]  Vladimir Kasyanov,et al.  Comparison of biomechanical and structural properties between human aortic and pulmonary valve. , 2004, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[19]  Michael S. Sacks,et al.  Design and Hydrodynamic Evaluation of a Novel Pulsatile Bioreactor for Biologically Active Heart Valves , 2004, Annals of Biomedical Engineering.

[20]  R Langer,et al.  Morphologic and mechanical characteristics of engineered bovine arteries. , 2001, Journal of vascular surgery.

[21]  D J Mooney,et al.  Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions. , 2000, Journal of biomechanical engineering.

[22]  M. Thubrikar.  The Aortic Valve , 1990 .

[23]  HirotoUeba,et al.  Shear Stress as an Inhibitor of Vascular Smooth Muscle Cell Proliferation , 1997 .

[24]  J. Ricotta,et al.  Effect of pressure on cultured smooth muscle cells. , 1997, Life sciences.

[25]  Michael S Sacks,et al.  The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. , 2005, Biomaterials.

[26]  J E Mayer,et al.  New pulsatile bioreactor for in vitro formation of tissue engineered heart valves. , 2000, Tissue engineering.

[27]  A. Schned,et al.  Tissue-shrinkage correction factor in the calculation of prostate cancer volume. , 1996, The American journal of surgical pathology.

[28]  S Jockenhoevel,et al.  CARDIOVASCULAR TISSUE ENGINEERING: A NEW LAMINAR FLOW CHAMBER FOR IN VITRO IMPROVEMENT OF MECHANICAL TISSUE PROPERTIES , 2000, ASAIO journal.

[29]  J D Hellums,et al.  Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. , 2000, American journal of physiology. Heart and circulatory physiology.

[30]  David J. Mooney,et al.  Cyclic mechanical strain regulates the development of engineered smooth muscle tissue , 1999, Nature Biotechnology.

[31]  Mark Eastwood,et al.  New multi-cue bioreactor for tissue engineering of tubular cardiovascular samples under physiological conditions. , 2004, Tissue engineering.

[32]  Yuichi Ueda,et al.  Novel pulse duplicating bioreactor system for tissue-engineered vascular construct. , 2004, Tissue engineering.

[33]  Vladimir Mironov,et al.  Perfusion Bioreactor for Vascular Tissue Engineering with Capacities for Longitudinal Stretch , 2003, The Journal of craniofacial surgery.

[34]  F P T Baaijens,et al.  The relevance of large strains in functional tissue engineering of heart valves. , 2003, The Thoracic and cardiovascular surgeon.