title: 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 x 7.5 x 2mm) 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<0.01), and that they developed directional anisotropy by 3 weeks of incubation (stiffer AF, p<0.01). In contrast, both dynamically flexed and static PGA/P4HB scaffolds exhibited a trend of decreased stiffness with incubation, with no development of directional anisotropy. Dynamically flexed PGA/P4HB scaffolds were significantly less stiff than static controls at 3 weeks (p<0.05). Scanning electron microscopy revealed signs of heterogeneous P4HB coating and fiber disruption, suggesting possible explanations for the observed mechanical properties. These results indicate that dynamic flexure can produce quantitative and qualitative changes in the mechanical properties of TEHV scaffolds, and suggest that these differences need to be accounted for when comparing the effects of mechanical stimulation on the development of cell-seeded TEHV constructs.
authors.affiliation: Engineered Tissue Mechanics Laboratory, McGowan Institute for Regenerative Medicine, Department of Bioengineering, University of Pittsburgh, 100 Technology Drive, Room 250, Pittsburgh, PA 15219, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Engelmayr
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hildebrand
authors.forename: Fraser W H
authors.initials: FW
authors.lastname: Sutherland
authors.forename: John E
authors.initials: JE
authors.lastname: Mayer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sacks
mesh_terms: D020341:Absorbable Implants; D004548:Elasticity; D004867:Equipment Design; D019544:Equipment Failure Analysis / Q000295:instrumentation / Q000379:methods; D005109:Extracellular Matrix / Q000737:chemistry; D006350:Heart Valve Prosthesis; D008422:Materials Testing / Q000295:instrumentation* / Q000379:methods*; D010812:Physical Stimulation / Q000295:instrumentation* / Q000379:methods*; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*