published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

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The major impact of this research lies in the aspect of improved design and long term biocompatibility of materials used for implants. There are two goals in this research. The first goal is to develop a methodology to quantitatively measure cell-material adhesion. The second goal is to obtain fundamental understanding of cell-material adhesion mechanisms. A rotating parallel disk is used to measure cell adhesion. The rotational system applies a controlled shear stress to the cultured cells. The shear stress experienced by the cells varies with radial location, being highest at the edge and zero at the disk?s center. There is a critical point along the radius where the shear stress experienced by the cells equals their adhesion strength. The cells outside it are removed and the cells inside it remain attached to the surface. NIH 3T3 Swiss mouse fibroblasts and chick retina neuron cells from 6-day embryos are used in this study. The fibroblasts were cultured on poly(methyl methacrylate) (PMMA), polycarbonate (PC), and on gold coated poly(vinylidene fluoride) (Au/PVDF). The critical shear stress for fibroblasts was the lowest for PC with 5.09 dynes/cm2 and highest for PMMA with 21.0 dynes/cm2. This four-fold difference is mainly due to the chemical structure of PMMA which promotes higher cell adhesion when compared to PC. Neurons were cultured on poly-D-lysine coated glass to promote cell adhesion. The critical shear stress of neuron cells varied from 3.94 to 27.8 dynes/cm2 these values are directly proportional to the applied shear stress. The neuron adhesion plateau at ~27 dynes/cm2 which indicates the maximum adhesion strength of the neuron/poly-D-lysine coated glass pair. This thesis contains six chapters. Chapter I describes the importance of cell adhesion for biocompatibility. Chapter II describes in more detail the goals of this research and the expected results. Chapter III lists all the materials, equipment, and methods used in this study. The most significant results are summarized in Chapter IV. The observations and results obtained are explained in detail in Chapter V and Chapter VI describes the key outcomes as well as proposes questions for the advancement of this research.

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To ensure the effective and safe use of nanomaterials for medical applications, the biocompatibility of the materials must be tested with particular relevance to the environment in which the material is placed. In nanoparticle-based drug delivery, it is crucial to evaluate a nanoparticle???s biocompatibility to ensure minimal cytotoxicity. Of several types of nanoparticles, peptide-based nanoparticles have emerged as promising systems for targeted cancer therapy. Yet, the biocompatibility of many of these peptides and their assembled particles has not been studied. This thesis, summarizes the original contribution on the effective and safe use of the particular self/co-assembling, amino acid pairing peptides and some of their DEGylated forms (modified versions) as carriers for anticancer drug delivery application. Therefore, the biocompatibility of the self-assembling, amino acid pairing (AAP) peptides AC8, its two DEGylated forms, as well as two related peptides, EAK16-II and EK8, is systematically investigated. The toxicity of these peptides and their complexes with pirarubicin was tested against the human adenocarcinoma lung cancer cell line, A549.The biocompatibility of the peptide-drug co-assembling complexes is assessed and the potential of these five peptides as carriers for the hydrophobic anticancer drug pirarubicin is demonstrated. For the first time experimental results on cytotoxicity, haemolytic activity, red blood cell (RBC) aggregation, complement activation and anaphylotoxin activation as an end result of complement activity for these five AAP peptides is reported. AC8, the amino end DEGylated AC8 (NP-I) and EK might be strong candidates for hydrophobic drug delivery considering their lack of toxicity and the fact that they are not recognized as a foreign molecule, inducing no considerable immune reactions. These results provide a basis for in vivo experiments and predict minimal in vitro toxicity of these peptides based delivery systems.

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Purpose: To evaluate long-term biocompatibility, optical clarity and the efficacy of Perfluoropolyether (PFPE) polymer as a corneal inlay in humans. Materials and Methods: Corneas of 5 unsighted eyes of 5 patients received inlays: one patient selected as control. All were examined at baseline, immediately post-operative, 7 days and monthly thereafter for 12 months and at 3-monthly intervals for the next 12 months. Clinical evaluation includes detailed slit-lamp biomicroscopy, refraction, keratometry, corneal topography, and other routine ocular examinations. Results: Surgery was uneventful. None of the patients developed corneal oedema or increased vascularisation during study period. All corneas were clear except for minimal haze around the edge of the implant and mild interface reflectivity. Two patients developed epithelial erosion with minimal stromal involvement at 4 and 24 months post surgery resulted in removal of inlay. Inlays remained stable in position in all patients, however clarity has reduced (4% - 26%) gradually with time. We believe mechanical stress from inlay to the surrounding tissue triggered keratocyte activation and extra cellular matrix material deposits around inlay may be responsible for epithelial erosions as well as the reduction in inlay clarity. All test eyes showed acute myopic shift by 8.47D ?? 1.97 (mean ?? SD) following implantation. The epithelial pigment deposits were detected in all test patients following surgery, related to acute corneal curvature changes. The removal data from two patients showed the reversal of the refractive effect to preoperative levels. One patient followed up for an extensive period of 19 months post inlay removal demonstrated stable results. Conclusion: The PFPE inlays have demonstrated excellent biocompatibility within the human corneal tissue for 2 years. The epithelial erosion and inlay clarity reduction were the two major problems encountered in this study. We believe these problems were related to the mechanical stress induced tissue response from inlay. Critical patient selection and the modification of inlay design should improve the success of the procedure. Inlays are effective in altering the refractive status of the eye by altering the anterior corneal curvature. Also, inlay implantation and removal procedures are found to be easy, safe and quick without any complications.