|Abstract:||The current designs of new biomaterials for bone substitutes or scaffolds focus on achieving biocompatibility and sufficient mechanical properties. In this thesis, we investigated the biocompatibility of synthetic polymers called aromatic thermosetting copolyesters (ATSP) as potential biomaterials for bone replacements (implants). These materials are easy to manufacture and have good mechanical properties such as high tensile strength, and high wear resistance. They can be made into bulk, film, foams, and composites. In this thesis, we included all these forms and created a composite by infusing ATSP with 10wt% of hydroxyapatite (minerals of similar compositions as those found in bone). Homogenous distribution of the HA filler improves the physical properties of composite ATSP. In addition to this, having robust adhesive features with metals, high energy absorption limit, and promising tribological properties makes ATSP a strong candidate for different orthopedic implant applications.
This research extended an earlier biocompatibility study of ATSP in which direct contact of fibroblasts cells was used to study of neat ATSP and ATSP blends with ultrahigh molecular weight polyethylene (UHMWPE) for total joint arthroplasty. The results demonstrated that cells were able to attach to ATSP, and there was no indication of cell death . Since these previous results looked promising, in this thesis we conducted more extensive studies of the biocompatibity of ATSP.
Chapter 1 describes the biocompatibility investigation of three different compositions (film, bulk, and foam) of neat and composite ATSP by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT assay) with human osteoblast cell line (hFOB 1.19 (ATCC® CRL 11372™)), and the results were obtained from the metabolic activity of hFOB 1.19 cells for 48 hours. The results which were either equal to or greater than 85% were accepted as non-cytotoxic, the values between 60% and 85% were defined as slightly cytotoxic, 30%– 59% were moderately cytotoxic and less than 30% were accepted severely cytotoxic. The results of metabolic activity by MTT showed that each group (film, bulk, and foam) of neat and composite ATSP samples did not demonstrate any toxicity at all concentrations (≥85%) except for neat film samples which showed slight toxicity (~75%). Overall the results for each group were consistent between neat and composite samples. Furthermore, the increase in the concentration did not change the results. The presence of HA was used to investigate the effect of HA on increasing the metabolic cell activity; however, there was no increase in cell activity with the presence of the HA.
Chapter 2 highlights the neat and composite foams that were designed to analyze the effect of biomaterial physical features, including porosity and mineral content over the bone formation by human mesenchymal stem cells differentiation. The analysis was done by alamarBlue® and RT-PCR assays. The metabolic activity results of foam samples by alamarBlue® with MSCs showed that none of the samples demonstrated any toxic effect; the metabolic activity for all samples was higher than initial metabolic activity values. All samples allowed cell proliferation and cell growth. Also, not only mineralized samples but also osteogenic media positively affected the metabolic activity because the composite samples showed high metabolic activity than neat samples on the day seven. Also, samples in osteogenic media demonstrated the high metabolic activity in comparison with sample in growth media on day seven. RT-PCR results showed that the samples in osteogenic media showed upregulated pattern for all gene expressions. It could also be interpreted that neat and mineralized samples in combination with pure osteogenic media promoted osteogenesis and allowed new bone formation.