Development of functionally graded biomaterial scaffolds using selective laser sintering.
Date of Issue2010
School of Mechanical and Aerospace Engineering
Tissue Engineering (TE) aims to create biological substitutes to repair or replace failing organs or tissues due to trauma or ageing. One promising approach in TE is to grow cells on biodegradable scaffolds, which act as temporary supports for the cells to attach, proliferate and differentiate; after which the scaffold will degrade, leaving behind a healthy regenerated tissue. Tissues in nature, including human tissues, exhibit gradients across a spatial volume, in which each identifiable layer has specific functions to perform so that the whole tissue/organ can behave normally. Such a gradient is termed a functional gradient. A good TE scaffold should mimic such a gradient, which fulfils the biological, mechanical and anatomical requirements of the target tissue. Thus, the design and fabrication process of such scaffolds become more complex and the introduction of computer aided tools combined with rapid prototyping (RP) techniques will lend themselves well to tackle these issues. The challenge in fabricating functionally graded scaffolds (FGS) using RP techniques lies in the development of suitable computer aided systems to facilitate the FGS design. What have been missing are the appropriate models that relate the scaffold physical properties, e.g. pore size and porosity, to the biological and mechanical requirements for the regeneration of the target tissue. The establishment of these relationships will provide the foundation to develop better computer aided systems to help design a suitable customized FGS. Computer Aided System for Tissue Scaffolds (CASTS) is a system consisting of a parametric library of polyhedral unit cells that can be assembled into a tissue scaffold. The existing CASTS system only allows the design of scaffolds with uniform porosity. Thus, this research focuses on the development of automated system based on CASTS for designing customized FGS intended for bone applications. The first step to the establishment of such system was the derivation of relationships between scaffold structure, porosity and compressive stiffness for polyhedral CASTS scaffolds fabricated using SLS. Based on the modified rule of mixtures, the compressive stiffness of the CASTS scaffolds could be predicted when the scaffold porosity is known. The next step was the integration of the porosity-stiffness relationships into the automated system algorithms. Such algorithms for designing FGS, both radial gradients for long bone applications and linear gradients for short or irregular bone regeneration have been achieved. A new cellular unit for constructing radial FGS, which was the unit cylinder, was introduced. A complete model relating the FGS parameters to the unit cell dimensions and assembly has also been established. The feasibility of the automated FGS system was verified using case studies of femur and mandible FGS. Selective Laser Sintering (SLS) was used to fabricate the scaffolds, and polycaprolactone (PCL) and polycaprolactone/hydroxyapatite (PCL/HA) were used as the scaffold materials. This automated FGS system is beneficial in aiding tissue scaffold designers in creating scaffolds with gradients mimicking the target organ. With the inputs of the scaffold stiffness variations and dimensions, the system alleviates the tedious drawing routines and the dependency on the user‟s computer skill. Finally, in vitro studies investigating the effects of varying scaffold porosity on cell proliferation and matrix mineralization were carried out. It was found that varying scaffold porosity varied scaffold surface area, which in turn affected the cell proliferation and function. The cell number on the scaffolds corresponded proportionally with the surface area of the scaffold, as well as the calcium content of the extra cellular matrix (ECM). Three-dimensional scaffold structure was proven to be a necessity for cell function, such as ECM deposition and mineralization, reflected by the significantly higher calcium deposit-to-cell number ratio of all scaffolds compared to those of two-dimensional polystyrene well. As time progressed, tetrazolium dye MTT (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) results and scanning electron microscopy (SEM) observation showed that the cells were able to attach and proliferate, forming multiple cell layers and infiltrating the scaffold‟s micro pores. This implied that SLS-sintered scaffolds could provide a favorable environment for the cells to attach, proliferate and deposit mineralized matrix for a prolonged period.