Objectives: The aim of this study was to develop a decision support tool to assess the potential benefits and costs of new healthcare interventions.

Methods: The Canadian Partnership Against Cancer (CPAC) commissioned the development of a Cancer Risk Management Model (CRMM)—a computer microsimulation model that simulates individual lives one at a time, from birth to death, taking account of Canadian demographic and labor force characteristics, risk factor exposures, and health histories. Information from all the simulated lives is combined to produce aggregate measures of health outcomes for the population or for particular subpopulations.

Results: The CRMM can project the population health and economic impacts of cancer control programs in Canada and the impacts of major risk factors, cancer prevention, and screening programs and new cancer treatments on population health and costs to the healthcare system. It estimates both the direct costs of medical care, as well as lost earnings and impacts on tax revenues. The lung and colorectal modules are available through the CPAC Web site (www.cancerview.ca/cancerrriskmanagement) to registered users where structured scenarios can be explored for their projected impacts. Advanced users will be able to specify new scenarios or change existing modules by varying input parameters or by accessing open source code. Model development is now being extended to cervical and breast cancers.

Polycaprolactone is a bioresorbable polymer that has potential for tissue engineering of bone and cartilage. In this work, we report on the computational design and freeform fabrication of porous polycaprolactone scaffolds using selective laser sintering, a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to designed porous architectures and computationally predicted properties. Compressive modulus and yield strength were within the lower range of reported properties for human trabecular bone. Finite element analysis showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Scaffolds were seeded with BMP-7 transduced fibroblasts and implanted subcutaneously in immunocompromised mice. Histological evaluation and micro-computed tomography (μCT) analysis confirmed that bone was generated in vivo. Finally, we have demonstrated the clinical application of this technology by producing a prototype mandibular condyle scaffold based on an actual pig condyle.

Because cells can recognize and attach to short synthetic peptides containing the tripeptide sequence, arg-gly-asp (RGD), we have designed peptides which will spontaneously bind and present an active RGD sequence on biomaterial surfaces. We have analyzed a number of synthetic peptides and fully characterized one which fulfills this functional criteria. This peptide has been named PepTite-2000™. When biomaterials are placed in aqueous buffers containing PepTite-2000, the peptide rapidly binds to the surface and provides a site for cell attachment. Cell attachment occurs to PepTite-2000 coated materials by an RGD dependent mechanism using the αvβ3 integrin. This coating protocol is widely applicable, and the peptide will coat and promote cell attachment to all the commonly used biomaterials we have tested including dacron, teflon, titanium and silicone. Analysis of the soft tissue response to dacron implants coated with PepTite-2000 demonstrates that the coating results in more rapid tissue ingrowth and less giant cell recruitment around the implanted materials. These data demonstrate that PepTite-2000 can be used to modify biomaterial surfaces and present a more “natural” site for cell interactions.

The effects of nitrogen ion implantation of Ti-6AI-4V alloy on growth of Pseudomonas aeruginosa bacteria on surfaces of the alloy have been investigated. Results for ion implanted samples were compared with controls with similarly smoothly polished surfaces and with controls that had intentionally roughened surfaces. The test consisted of exposing sterile alloy samples to a microbiological broth, to which 24 hour-old cultures of Pseudomonas aeruginosa had been added. After bioassociation at normal temperature 37°C, bacteria adhering to the surface were fixed and treated with a new ruthenium tetroxide staining method, and quantified by use of scanning electron microscopy (SEM), back-scattered electron imaging and EDAX energy dispersive microanalysis. For smooth samples of the alloy, after a 12 hour growth period, the retained bacteria (revealed by the biologically incorporated ruthenium), decreased monotonically with nitrogen dose out to a total fluence of approximately 7 × 1017/cm2 in an affected depth of approximately 0.1500 μm. The SEM confirmed that the Pseudomonas aeruginosa adhered equally to control materials. The ruthenium studies revealed that the amount of bacterial adhesion is indirectly proportional to the nitrogen ion implantation of the titanium. The greater the percentage of nitrogen ion implantation in the titanium alloy, the less bacteria colonized the disk.

A Warren-Averbach1-4 X-ray line profile analysis was applied to broadened X-ray diffraction peaks from copper deformed in fatigue. The copper specimens were fatigued by four-point bending at peak-strain amplitudes between 0.00105 and 0.00442 in./in., and measurements were made at various fractions of the total fatigue life. The analysis results in an estimation of (a) an average coherently diffracting domain size normal to the diffracting planes and (b) an rms strain distribution function where the strain normal to the diffracting planes is averaged over a given distance at all points in the diffracting crystals and expressed as a function of averaging distance.

Prior to fatigue cycling, the annealed copper exhibited extinction, which reduced the integrated intensity from the low-angle reflections. After fatigue cycling, the integrated intensity increased with increasing strain amplitude of fatigue. The integrated intensities and the rms strains were established during the first few percent of the fatigue life and were found to increase with fatigue strain amplitude. The measured strains were larger in the <100> direction than in the <111> direction, but the absolute values were small. On the basis of transmission electron microscopy of thin foils, these results may be explained by assuming the strains are due to the presence of numerous dislocation dipoles.