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Title: Improvement of biomaterials properties using plasma-based technology
Other Titles: Deng li zi ti ji shu ti gao sheng wu cai liao xing neng
Authors: Jin, Weihong (金衛紅)
Department: Department of Physics and Materials Science
Degree: Doctor of Philosophy
Issue Date: 2015
Publisher: City University of Hong Kong
Subjects: Biomedical materials
Plasma engineering
Notes: CityU Call Number: R857.M3 J56 2015e
x, 194 pages : illustrations (some color) ; 30 cm
Thesis (Ph.D.)--City University of Hong Kong, 2015.
Includes bibliographical references.
Type: Thesis
Abstract: Biodegradable metals and cationic polymers are promising in biological applications for tissue engineering and gene delivery, respectively. Magnesium alloys are attractive to biomedical applications such as cardiovascular stents and orthopedic implants due to the nature degradability and similar Young's modulus. However, the major limitation is the rapid degradation rate in the physiological environment. Gene and drug vectors play a key role in gene and chemotherapeutic treatment. Cationic polymers have low immunogenicity and toxicity, and large loading capacity. However, their typically low delivery efficiency is the major problem. Metallic elements with good biocompatibility play essential roles in biological systems and activities and some metal nitrides and oxides typically possess good anticorrosion properties. Hence, metallic elements are expected to be incorporated into biomaterials to improve the biological properties. Plasma-based techniques such as sputtering and ion implantation are very useful and effective for the improvement of material properties. Therefore, they are proposed to improve the surface anticorrosion and biocompatible properties of magnesium alloys and the delivery efficiency of cationic polymers. Due to the excellent anticorrosion properties of the transition metal nitride, a niobium nitride film is deposited on the WE43 magnesium alloy by reactive magnetron sputtering to improve the corrosion resistance. Without introducing extraneous elements, a small amount of neodymium (Nd) is introduced into the WE43 magnesium alloy by ion implantation to form a biocompatible oxide barrier against corrosion. As an extraneous but biocompatible element, Hafnium is also implanted into the WE43 magnesium alloy to improve the in vitro corrosion resistance and biocompatibility by the formation of oxide-containing layer. The composition, morphology, and surface energy are monitored to characterize the surface layer after modification. Electrochemical impedance spectroscopy, polarization tests, and immersion tests are systematically applied to determine the corrosion behavior. The in vitro cell adhesion and viability are also investigated to evaluate the biological response. Our results show the degradation of the WE43 magnesium alloy is significantly retarded in simulated body fluids and cell culture medium. Furthermore, obviously enhanced cell attachment and excellent biocompatibility are observed after surface modification. The apparent improvement of both corrosion resistance and in vitro biocompatibility is due to the formation of corrosion resistant and biocompatible surface layer. The degradation process and corresponding mechanism are investigated and interpreted. To produce a new type of gene vector with high gene transfection efficiency, Nd is incorporated into β-cyclodextrin-polyethylenimine (PC) by ion implantation. Nd-doped PEI-CyD (Nd-PC) exhibits a significantly enhanced transfection efficiency compared to PEI-CyD and Lipofectamine 2000. The mechanism of remarkably enhancement of gene transfection efficiency is that Nd enhances cell uptake and regulates the cellular pathways. A three-layered multifunctional nanocarrier system PCD/siRNA/Nd-PC is also formed by mixing Doxorubicin (Dox)-loaded PC (PCD) with siRNA and further coating with Nd-PC. This multifunctional nanocarrier system with much lower doses of chemotherapeutic drugs and siRNA exhibits significantly effective antitumor therapy in a mouse tumor model. The trace amount of Nd regulates the cellular pathways and enhanced endocytosis for the more effective penetration of nanocarriers, which is supported by the down-regulation of CaM and up-regulation of caveolinl and clatherin mRNA and proteins in vitro and in vivo. This leads to extremely enhancement of the cellular uptake of siRNA and Dox, then effective siRNA silencing, enhanced intercellular concentration of Dox, enhanced cell apoptosis, and following enhanced anticancer therapy. In summary, plasma-based modification is an effective way to improve the corrosion resistance and biocompatibility of the biomedical magnesium implants, and provides a new strategy to prepare highly effective metal-incorporated non-viral gene vectors.
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