Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [263]-275).

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by Pang Sai Yau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves [87-90]). / Chapter chapter one： --- introduction / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- biology of cancellous bone grafts --- p.2 / Chapter 1.2.1 --- Biology of bone graft incorporation --- p.2 / Chapter 1.2.1.1 --- Osteogenesis --- p.2 / Chapter 1.2.1.2 --- Vascularization --- p.3 / Chapter 1.2.1.3 --- Osteoinduction --- p.3 / Chapter 1.2.1.4 --- Osteoconduction --- p.4 / Chapter 1.2.2 --- Histological changes of bone grafts after bone transplantation --- p.4 / Chapter 1.2.2.1 --- Histologic pictures of cancellous autograft --- p.4 / Chapter 1.2.2.2 --- Histologic pictures of cancellous bone allograft --- p.5 / Chapter 1.2.2.3 --- Summary of the histologic changes of bone grafts --- p.5 / Chapter 1.3 --- application of cancellous bone grafts --- p.6 / Chapter 1.3.1 --- Principles of graft incorporation --- p.6 / Chapter 1.3.1.1 --- Operative site --- p.6 / Chapter 1.3.1.2 --- Graft material --- p.7 / Chapter 1.3.1.2.1 --- Autogenic cancellous bone --- p.8 / Chapter 1.3.1.2.2 --- Autogenic cortical bone --- p.9 / Chapter 1.3.2.2.3 --- Vascularized autogenic bone grafts --- p.9 / Chapter 1.3.2.2.4 --- Bone allografts --- p.10 / Chapter 1.3.2.2.5 --- Graft adjuncts and substitutes --- p.11 / Chapter 1.3.2.3 --- Systemic factors influencing gaft incorporation --- p.13 / Chapter 1.3.2.4 --- Local factors influencing graft incorporation --- p.13 / Chapter 1.3.3 --- Bone graft complications --- p.13 / Chapter 1.3.4 --- Placement of a graft --- p.14 / Chapter 1.3.5 --- Bone graft harvesting --- p.15 / Chapter 1.3.5.1 --- Iliac bone graft --- p.15 / Chapter 1.3.5.2 --- Femoral head bone allograft --- p.16 / Chapter 1.4 --- Application of flow conductance concept in a cancellous bone graft --- p.17 / Chapter 1.4.1 --- Physical structure of cancellous bone --- p.17 / Chapter 1.4.2 --- Porosity of cancellous bone --- p.17 / Chapter 1.4.3 --- Flow conductance concept --- p.18 / Chapter chapter two： --- material and method / Chapter 2.1 --- Transplantation of cancellous bone graft - Rabbit model --- p.19 / Chapter 2.1.1 --- Preparation of porcine cancellous bone graft --- p.19 / Chapter 2.1.1.1 --- Bone drilling --- p.19 / Chapter 2.1.1.2 --- Defat and freeze-dry --- p.20 / Chapter 2.1.2 --- Flow conductance measurement --- p.21 / Chapter 2.1.2.1 --- Porosity measurement --- p.21 / Chapter 2.1.2.2 --- Conductance measurement --- p.24 / Chapter 2.1.3 --- Rabbit model --- p.26 / Chapter 2.1.4 --- Methods of assessment --- p.29 / Chapter 2.1.4.1 --- Intraosseous pressure measurement --- p.29 / Chapter 2.1.4.2 --- Histologic study --- p.30 / Chapter 2.1.4.3 --- Blood flow study - use of tracer microspheres --- p.30 / Chapter 2.2 --- Flow conductance measurement of human cancellous bone --- p.34 / Chapter chapter three： --- results / Chapter 3.1 --- Results of the effects of various conductance of the grafts on bone healing in animal model --- p.38 / Chapter 3.1.1 --- Intraosseous pressure measurement --- p.38 / Chapter 3.1.2 --- Histological study --- p.40 / Chapter 3.1.3 --- Blood flow study of cancellous bone grafts --- p.52 / Chapter 3.2 --- Human specimens study --- p.62 / Chapter chapter four： --- discussion / Chapter 4.1 --- Discussion of the results in vivo study --- p.66 / Chapter 4.1.1 --- Intraosseous pressure measurement - a baseline study --- p.66 / Chapter 4.1.2 --- Effects of flow conductance of porcine cancellous grafts on bone regeneration --- p.67 / Chapter 4.1.2.1. --- Threshold conductance --- p.67 / Chapter 4.1.2.2. --- Histological score --- p.68 / Chapter 4.1.3 --- Discussion of graft healing from the blood flow study --- p.70 / Chapter 4.1.3.1 --- Tibia blood supply in relation to bone healing --- p.70 / Chapter 4.1.3.2 --- Effect of different flow conductance on blood flow changes in the tibia-graft structure --- p.72 / Chapter 4.1.4 --- "Comparison of length, porosity and conductance as the parameter on graft healing" --- p.74 / Chapter 4.2 --- Discussion on human bone specimens study --- p.76 / Chapter 4.3 --- General discussion --- p.78 / Chapter 4.3.1 --- The limitation of the animal model --- p.78 / Chapter 4.3.2 --- Some problems related to the clinical aspects --- p.79 / Chapter chapter five： --- conclusion --- p.81

Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 216-234).

Over the last few decades, miniaturization of the product became a necessity for many industries to achieve successful technological development, satisfy customer needs, and stay economically competitive in the market. Thus, many medical, aerospace, and electronic devices tend to decrease in size. Along with the strong demand for miniaturization, new cutting-edge micromanufacturing techniques are developing in order to produce microcomponents with a smooth surface finish and high dimensional accuracy. In the medical industry, some devices require manufacturing of fluidic microchannels on biocompatible materials for transportation of exact amount of medicine to a defined location. Often such microchannels must be manufactured to achieve a high aspect ratio, a submicron surface finish, and an anisotropic controlled profile. The fabrication of such channels on biocompatible materials still poses a challenge. This study developed micromanufacturing technique to produce the microchannels and satisfy all the requirements listed above. Computer controlled micromilling on a high speed machine system in minimum quantity lubrication was used to remove most materials and define a channel pattern. Microchannels were machined with ball end mills of diameters from Ø152μm to Ø198μm on NiTi alloy, 304 and 316L stainless steels. Assessment of microchannel was performed with optical microscopy, scanning electron microscopy, and white light interferometry. The theoretical surface roughness in ball end milling was derived using geometrical approach. The theoretical surface finish model was compared and validated with the experimental surface finish data. Meso- and macro-scale milling confirmed the validity of the model, but surface finish in micro-scale milling was measured to be a few orders of magnitude higher due to size effect and build-up edge. The build-up-edge was reduced when using AlTiN coated tools and milling in minimum quantity lubrication. The empirical surface roughness model obtained in this study shows the dependence of surface finish on chip load in micromilling. In order to further enhance the surface finish of milled microchannels additional finishing technique was identified. A separate study developed an effective electrochemical polishing technique to remove burrs and enhance surface finish of milled microchannels. When applying to 304, 316L stainless steel alloys and NiTi alloy, this hybrid technique can repeatedly produce microchannels with an average surface finish less than 100nm.

Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.

Abstract The shape memory effect, superelasticity, and good damping properties, uncommon in other implant alloys, make the nickel-titanium shape memory metal alloy (Nitinol or NiTi) a fascinating material for surgical applications. It provides a possibility to make self-locking, self-expanding and self-compressing implants. The purpose of this work was to determine if NiTi is a safe material for surgical implant applications. The primary cytotoxicity and the corrosion rate of NiTi were assessed in human osteoblast and fibroblast cell cultures. Comparisons were made with 316 LVM stainless steel (StSt) and pure titanium. The metal ions present in the media were analyzed using atomic absorption spectrometry (GFAAS). Despite the higher initial nickel dissolution, NiTi induced no toxic effects, decrease in cell proliferation or inhibition in the growth of cells in contact with the metal surface. The general soft tissue responses to NiTi were compared to corresponding responses to StSt and Ti-6Al-4V alloy in rats during a follow-up of 26 weeks. The muscular tissue response to NiTi was clearly non-toxic and non-irritating, as were also the neural and perineural responses. The overall inflammatory response and the presence of immune cells, macrophages and foreign body giant cells were similar compared to the other test materials. At 8 weeks, histomorphometry showed that the encapsule membrane of NiTi was thicker than that of stainless steel, but at 26 weeks the membrane thicknesses were equal. A regional acceleratory phenomenon (RAP) model was used to evaluate new bone formation, bone resorption and bone (re)modeling after periosteal implantation of NiTi, StSt or Ti-6Al-4V in rats using histomorphometry. Maximum new woven bone formation started earlier in the Ti-6Al-4V group than in the NiTi group, but also decreased earlier, and at 8 weeks the NiTi and StSt groups had greater cortical bone width. Later, no statistical differences were seen. NiTi had no negative effect on total new bone formation or normal RAP during a 26-week follow-up. The ultrastructural features of cell-NiTi adhesion were analyzed with scanning electron microscopy (FESEM). Cell adhesion and focal contacts showed a good acceptance of NiTi. Femoral osteotomies of rats were fixed with either NiTi or StSt intramedullary nails. Bone healing was examined with radiographs, peripheral quantitative computed tomography (pQCT) and histologically. The maximum follow-up was 60 weeks. There were more healed bone unions in the NiTi than the StSt group at early time points. Callus size and bone mineral density did not differ between the NiTi and StSt groups. Mineral density in both groups was lower in the osteotomy area than in the other areas along the nail. Density in the nail area was lower than in the proximal part of the operated femur or the contralateral femur. Bone contact to NiTi was close, indicating good tissue tolerance. Determination of trace metals from several organs was done by GFAAS or inductively coupled plasma-atomic emission spectrometry (ICP-AES). There were no statistically significant differences in nickel concentration between the NiTi and StSt groups in distant organs. The FESEM assessment showed surface corrosion changes to be more evident in the StSt implants. On the basis of this study, the biocompatibility of NiTi seems to be similar to or better than that of stainless steel or Ti-6Al-4V alloy. NiTi appears to be suitable for further use as a biomaterial, because its biocompatibility is good. When NiTi is intended to be used in long-term implants, optimal surface treatment must consider.