Electrospinning controlled architecture scaffolds for tissue engineering and the effect of scaffold mechanical properties on collagen synthesis in tissue engineered mitral valves

The engineering of substitute heart valves using biodegradable scaffolds and autologous cells has undergone considerable advances in recent years. Research conducted attempting to optimize cell source and culturing techniques for developing functional tissues has had promising results. However, in vivo studies resulted in valves that did not perform as well as the native valves they were intended to replace.; The success of the tissue-engineered valve substitutes has been shown to be dependent on several factors including cell type, scaffold material, scaffold morphology and mechanical conditioning. The leaflets of these valves use either porous scaffolds or fibro-porous scaffolds with random fiber orientations. Native heart valves have fibrous extracellular matrices that consist of collagen and elastin oriented in specific directions with respect to the valve tissue regional loading. It is speculated that one reason for the failure of tissue-engineered valves is that the scaffolds used to generate the tissue do not facilitate the proper development of the collagen and elastin architecture. Using scaffolds that have similar architectural features and mechanical properties of the native valve may facilitate the development of the extracellular matrix, thus increasing the success rate of the engineered tissue substitutes.; The intent of this research is to investigate for the mitral valve anterior leaflet the dependence of collagen synthesis on scaffold mechanical properties and morphological features. To accomplish this, a unique device was developed to produce controlled architecture fibro-porous scaffolds using an electrospinning technique. To achieve reproducible scaffolds the dependence of scaffold fiber diameter and spacing on electrospinning parameters were investigated. The results from the parameterization were used to produces scaffolds from biodegradable polyurethane with specific architectural features and different mechanical properties. The scaffolds were seeded with valvular interstitial cells and cultured under static conditions after which uniaxial cyclic strain was applied to the seeded scaffolds.; Results from the electrospinning parameterization indicate that the fiber collection surface is more influential on fiber diameter and spacing than the accepted parameters known to effect electrospun fiber morphology. Biochemical analysis revealed that collagen synthesis and content may be dependent on the stress strain relationship and stiffness of the scaffold in tissue-engineered constructs.