Abstract
The use of stem cells in tissue engineering has emerged as a promising therapy for the repair of bone and cartilage defects. Targeted delivery of stem cells requires a substrate to maintain the cells at the repair site, as well as to provide the physical cues, such as mechanical strain, for encouraging differentiation and expression of the mature cell phenotype. The strains that will be generated in cells residing on the scaffold is dependent on the scaffold material, as well as both the fibre thickness and the fibre orientation in the scaffold. To encourage uniform bone matrix generation throughout the scaffold, it is desirable that the strain be uniformly distributed and that the internal pore architecture be precisely controlled to maximise media diffusion. This requires an optimised scaffold design and a manufacturing technique that allows for precise control over the scaffold’s internal architecture.
Scaffold architecture was optimised by performing a series of finite element analyses (FEA) on computer aided design (CAD) models of Polycaprolactone (PCL) scaffolds. The mechanical properties of PCL were used to yield an accurate strain profile of scaffolds with different fibre orientations. Having determined the optimal scaffold geometry, PCL scaffolds were manufactured using a fibre deposition technique that yielded three-dimensional objects with this geometry. During manufacture, a PCL solution was extruded into a non-miscible solvent which precipitated out PCL fibres in repetitive layers. Of the geometries tested with FEA, a 90 degree rotation of adjacent layers with a 50% offset of parallel strands was found to provide the optimal strain distribution (60% increase in surface exposed to strain). Histomorphometry was used to assess the exact dimensions of the scaffold produced. Fibre spacing was found to be precisely controlled to 380 +/- 10 microns within the layers and the fibre thickness was controlled to 270 +/- 10 microns.
This demonstrates that FEA can be used to predict the strain distribution of different CAD models and that the fibre deposition solvent extrusion technique can be used to accurately manufacture PCL scaffolds that match the desired architecture.
Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.