Development Of Novel High Strength Composite Calcium Phosphate Cement For Orthopedic Applications

Author : Mehrnaz Salarian
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (16 download)

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Download or read book A New Generation of Polymer/ceramic Composite Biomaterials for Bone Regeneration written by Mehrnaz Salarian and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a substantial emerging interest for fundamental and applied research on the reinforcement of polymeric materials using nanotechnology. In the biomedical industry, development of novel bone cement composite materials with enhanced mechanical properties is of tremendous potential importance. The most universally used injectable bone cement is made of poly(methyl methacrylate) (PMMA); however, the major disadvantage of PMMA is its non-biodegradability. Polymers such as poly(propylene fumarate) (PPF) and polycaprolactone (PCL) are biodegradable, but suffer from a lack of mechanical properties. The aim of this research was to test the efficacy of these biodegradable polymers integrating nanotechnology for the development of composite biomaterials with improved mechanical properties sufficient for bone cements. This goal was investigated through a range of different studies. Focusing on nanostructured titania (n-TiO2) initially, titania nanofibers (n-TiO2 fibers) and nanowires (n-TiO2 wires) were introduced into a PPF matrix for potential use as an orthopaedic biomaterial to treat skeletal bone defects and diseases such as osteonecrosis. PPF was modified with maleic anhydride to provide functionality for the coordination of PPF to the surface of TiO2 nanofibers through a ring-opening reaction. The synthesis and modification of PPF were confirmed by NMR (1H and 13C) and XPS. The reaction chemistry of the functionalized PPF and nano-TiO2 was also investigated by XPS and FTIR analyses. The PPF-grafted nano-TiO2 was further employed in the development of bone cement composites by crosslinking/polymerization in the presence of N-vinyl pyrrolidone. Mechanical testing of the resulting bone cement composites demonstrated a significant enhancement of the tensile and flexural properties attributed to the chemical bonding between the PPF matrix and TiO2 nanofibers. On the basis of the determined mechanical properties, an optimum composition was found at 5 wt% loading of n-TiO2 fiber (0.5% in the starting composition) which provided a significant increase in Young's modulus (153%), tensile strength (113%), flexural modulus (196%), and flexural strength (126%) when compared with the unfilled PPF. These improvements were attributed to the chemical linkage of the filler to the polymer matrix which enhances the transfer of a mechanical load to the n-TiO2 fiber, leading to an increase in the mechanical properties of the bone cement composite. Secondly, bone formation is an angiogenesis-dependent process, and the need for treatment modalities that enhance neovascularization is especially important for bone regeneration in necrotic bone. A bone cement system capable of delivering an angiogenic modulator in a controlled manner may have the ability to boost the angiogenic response when injected to an osteonecrotic lesion. Therefore, an angiogenic agent, ginsenoside Rg1, was incorporated into an orthopedic PPF-based cement. Additionally, Sr-doped TiO2 nanofibers synthesized in supercritical CO2 were added to the cement formulation as an alternative radiopacifier to enable visualization of the bone cement composites and potential monitoring of the healing and loosening processes. XPS analysis showed that Sr2+ was doped in the crystalline matrix of anatase with the formation of SrTiO3. The strong nterfacial adhesion between PPF and nanofibers were characterized by SEM, FTIR, XPS, and thermal analyses and mechanical testing. The Sr-doped n-TiO2 fibers were shown to provide reasonably higher radiopacity to the PPF matrix, which is 0.32 ± 0.03 mm Al, than the unmodified fibers at the same loading level (0.20 ± 0.01 mm Al). In addition, bone cement composites loaded with ginsenoside Rg1 were found to provide a high drug release without sacrificing the mechanical properties of the bone cement. Furthermore, tube formation bioassays suggested that human umbilical vein endothelial cell lines would rearrange and align into a tubular structure in the presence of ginsenoside Rg1. Consequently, the proposed cement combines the immediate mechanical support given by the chemical bonding between the filler/polymer and optimum radiopacity (0.30 ± 0.12 mm Al) due to the incorporation of the Sr-doped TiO2 nanofibers to PPF matrix. Thirdly, because of the unique biological activities of ginsenoside Rg1, upregulating in vitro proliferation, migration, chemo-invasion, and tube formation in human umbilical vein endothelial cells (HUVECs), Rg1 can be incorporated into scaffold materials for bone tissue engineering applications. This incorporation could be achieved by encapsulation of ginsenoside Rg1 in biodegradable microspheres of PPF. Rg1-loaded PPF microspheres were prepared by both a double emulsion and a microfluidic technique for the first time in this research. The size and morphology of the Rg1-loaded PPF microspheres were characterized by SEM, showing unimodal 50-65?m size diameters using the microfluidic technique, ideal for easy flowing powders required in commercial formulations. The PPF microspheres produced from the microfluidic technique gave high encapsulation efficiencies of up to 95.35 ± 0.82%, while those obtained from a conventional double emulsion method gave a much broader size distribution in the range of 2-45?m with lower encapsulation efficiencies of 78.48 ± 1.68%. Release profiles were studied and quantified by UV-Vis spectrophotometry, with the results showing a lower initial burst in the release of Rg1 from the unimodal microspheres prepared by the microfluidic technique than from the double emulsion method. The burst effect was followed by a slow release profile which can be used for long term drug delivery applications to maintain the ginsenoside Rg1 concentration for an extended time period. Moreover, the released Rg1 showed a significant stimulatory effect on angiogenesis behavior and tube formation in human umbilical vein endothelial cells (HUVECs). Therefore, PPF microspheres developed in this study have potential for next-generation biomedical agents in drug-release devices for bone tissue engineering. Finally, the use of hydroxyapatite HAp is rather limited for heavy load-bearing applications due to low mechanical reliability and poor processability. Therefore, immobilization of a biocompatible metal/metal oxide on the surface of HAp has been receiving increased attention for applications involving the enhancement of mechanical properties of biocompatible prostheses. A novel nanostructured HAp and a composite of HAp and TiO2 with ultrafine structure and significantly improved mechanical properties were prepared using combined co-precipitation and sol-gel method in the green solvent, scCO2, and incorporated into polycaprolactone (PCL) matrix to develop scaffolds with enhanced physical and mechanical properties for bone regeneration. SEM and TEM analyses were employed to examine the morphology of the HAp nanoplates and HAp-TiO2 nanocomposites. The presence of Ti, O, Ca, and P in the HAp-TiO2 nanocomposites was detected by EDX. In addition, the effect of metal alkoxide concentration, reaction temperature, and pressure on the morphology, crystallinity, and surface area of the resulting nanostructured composites was examined using SEM, XRD, and the BET method. Chemical composition of the products were characterized using FTIR, XPS, and XANES analyses. TGA analysis was performed to investigate thermal behavior of the synthesized nanomaterials. Mechanical testing revealed a significant increase in the Young's modulus (88.6%), tensile strength (122%), flexural modulus (47%), and flexural strength (59.6%) of PCL/HAp-TiO2 composites containing 20 wt % HAp-TiO2 compared to PCL/HAp composites.