Preparation of advanced porous structures by stereolithography for application in tissue engineering

Abstract

Stereolithography is a solid freeform fabrication technique, with which computer-designed objects can be automatically fabricated from photo-curable polymer resins in a layer-by-layer manner. In tissue engineering, there is a need for porous structures with well-defined external geometries and internal pore architectures to serve as scaffolds, which are biodegradable support materials for the generation of new tissue by seeded cells. In this work we have developed several resins for use in a stereolithography apparatus to make such scaffolds. A poly(D,L-lactide)-based resin was prepared for making strong and rigid glassy materials, a poly(D,L-lactide-co--caprolactone)-based resin for flexible materials, a poly(ethylene glycol-co-D,L-lactide)-based resin for hydrogels and a resin based on poly(D,L-lactide) and micrometer-sized hydroxyapatite particles for composite materials suitable for bone repair. Using these resins, biodegradable structures with different designs were prepared with high precision and accuracy, as determined by micro-computed tomography. Their mechanical properties could be influenced by the choice of building material and by the architecture of the porous structure. Due to the well-defined architecture, the mechanical behaviour could be very well predicted using finite element modelling techniques. Designed gyroid structures prepared by stereolithography showed a permeability of one order of magnitude larger than salt-leached porous structures having similar porosity and pore size. This facilitated wetting and the homogeneous seeding of cells into the scaffolds, and enabled 5 days of static culture with high final cell densities in the core of 5 mm-sized gyroid scaffolds. The high freedom of design of the stereolithography technique also enabled the preparation of scaffolds with a gradient in pore size and porosity. In this way the flow profile throughout perfused scaffolds could be influenced by the pore architecture, and both homogeneous cell distributions as well as gradients therein could be accomplished using a perfusion bioreactor. The future use of stereolithography and the developed materials could lead to better solutions for regenerating failing tissues.