A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials.

Abstract Dynamic flexure is a major mode of deformation in the native heart valve cusp, and may effect the mechanical and biological development of tissue engineered heart valves (TEHV). To explore this hypothesis, a novel bioreactor was developed to study the effect of dynamic flexural stimulation on TEHV biomaterials. It was implemented in a study to compare the effect of uni-directional cyclic flexure on the effective stiffness of two candidate TEHV scaffolds: a non-woven mesh of polyglycolic acid (PGA) fibers, and a non-woven mesh of PGA and poly l -lactic acid (PLLA) fibers, both coated with poly 4-hydroxybutyrate (P4HB). The bioreactor has the capacity to dynamically flex 12 rectangular samples (25×7.5×2 mm) under sterile conditions in a cell culture incubator. Sterility was maintained in the bioreactor for at least 5 weeks of incubation. Flexure tests to measure the effective stiffness in the “with-flexure” (WF) and opposing “against-flexure” (AF) directions indicated that dynamically flexed PGA/PLLA/P4HB scaffolds were approximately 72% (3 weeks) and 76% (5 weeks) less stiff than static controls ( p p p

[1]  Ajit P. Yoganathan,et al.  Biosynthetic Activity in Heart Valve Leaflets in Response to In Vitro Flow Environments , 2001, Annals of Biomedical Engineering.

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

[3]  Robert M. Nerem,et al.  The Role of Matrix Metalloproteinase-2 in the Remodeling of Cell-Seeded Vascular Constructs Subjected to Cyclic Strain , 2001, Annals of Biomedical Engineering.

[4]  I Vesely,et al.  Analysis of the bending behaviour of porcine xenograft leaflets and of natural aortic valve material: bending stiffness, neutral axis and shear measurements. , 1989, Journal of biomechanics.

[5]  Joan E. Sanders,et al.  A device to apply user-specified strains to biomaterials in culture , 2001, IEEE Transactions on Biomedical Engineering.

[6]  C. M. Agrawal,et al.  The effects of dynamic compressive loading on biodegradable implants of 50-50% polylactic Acid-polyglycolic Acid. , 1996, Tissue engineering.

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

[8]  D L Bader,et al.  A system for monitoring the response of uniaxial strain on cell seeded collagen gels. , 2000, Medical engineering & physics.

[9]  M. Sacks,et al.  Effects of mechanical fatigue on the bending properties of the porcine bioprosthetic heart valve. , 1999, ASAIO journal.

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

[11]  C. M. Agrawal,et al.  Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering. , 2000, Biomaterials.

[12]  D. Mooney,et al.  Combining chondrocytes and smooth muscle cells to engineer hybrid soft tissue constructs. , 2000, Tissue engineering.

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

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

[15]  H. Alexander,et al.  Development and characterization of tissue-engineered aortic valves. , 2001, Tissue engineering.

[16]  R Langer,et al.  A biodegradable composite scaffold for cell transplantation , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  C. Vacanti,et al.  Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. , 2001, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[18]  Roland Hetzer,et al.  New pulsatile bioreactor for fabrication of tissue‐engineered patches , 2001 .

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

[20]  Michael S. Sacks,et al.  Dynamic In Vitro Quantification of Bioprosthetic Heart Valve Leaflet Motion Using Structured Light Projection , 2001, Annals of Biomedical Engineering.

[21]  Frederick J Schoen,et al.  Cardiovascular tissue engineering. , 2002, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[22]  R Langer,et al.  Surface hydrolysis of poly(glycolic acid) meshes increases the seeding density of vascular smooth muscle cells. , 1998, Journal of biomedical materials research.