published_or_final_version / Dentistry / Master / Master of Dental Surgery

The golden method of peripheral nerve system injury is the nerve autograft, but it is associated with drawbacks such as donor site morbidity, needs of second incisions and the shortage of nerve grafts. Comparatively, connecting the nerve defect directly is an alternative. Unfortunately, if the defects are long, the induced tension will deteriorate the nerve regeneration. These limitations led to the development of artificial nerve guidance conduit (NGC). The market available NGC have problems of unsatisfactory functional recovery and may collapse after the implantation. These are attributed to material and structural deficiencies. Therefore, there is essential to study a biomaterial, which has excellent biological and physical properties to fit the NGC application. In addition, some studies suggested that the poor functional recovery resulted from the NGC implantation were due to the lack of micro-guidance inside the conduit. Thus, it is necessary to investigate the structural influence on the functional recovery of peripheral nerve injury. Crosslinked urethane-doped polyester elastomer (CUPE) is newly invented for a blood vessel graft because it possesses similar mechanical properties of blood vessel which is similar to nerve as well. Therefore, CUPE was also considered to be the NGC. Its biocompatibility has been proved to be excellent in the previous study done by Dr. Andrew SL, Ip. Targeting on the long peripheral nerve regeneration, the aims of this study are (1) to investigate the biocompatibility of CUPE in in-vitro condition and (2) to study the influence of nerve-like structure on the peripheral nerve system injury in an animal model. The ultimate goal is to enhance the functional recovery of peripheral nerve system injury by implanting a flexible biomaterial, CUPE, which has a nerve-like microarchitecture. It is hypothesized that the nerve-like structure can promote the axonal regeneration. The surface energy and roughness of CUPE were investigated. It showed a relatively low surface energy compared to other conventional biopolymers such that the cell adhesion and also the proliferation were inhibited. Therefore, the CUPE was modified by the immersion into a high glucose DMEM. The change in the hydrophilicity, roughness and cell viability of medium treated CUPE were studied. The hydrophilicity of treated CUPE was increased but the roughness was remaining unchanged whereas the pH of the immersion solution did not cause any effect on the cell activity on the CUPE. In the pilot animal study, five channels along the CUPE-NGC had a similar myelinated fiber density and population compared to the nerve autograft. Also, the channels in the CUPE-NGC were fragmented. In summary, the medium treatment could enhance the hydrophilicity of CUPE and the cell activity on CUPE. Such modifications did not governed by the pH of the medium. The NGC-CUPE with five channels, which imitated a basic nerve structure was shown to have a similar tissue regeneration and the functional recovery as the nerve autograft did. The results proved the hypothesis that the nerve-like structure can promote the functional recovery of peripheral nerve system injury with the use of a new biomaterial, CUPE as the NGC substrate. / published_or_final_version / Orthopaedics and Traumatology / Master / Master of Philosophy

One of the main problems in healthcare is the loss or failure of organs or tissues resulting from diseases, post-surgery complications, trauma or organ failure. As a result of tissue and organ shortage, there is a need for biomaterials designed to promote tissue regeneration resulting in good quality repair of tissues or organs, to maintain or repair biological function. Collagen, as one of the main proteins in the human body, has been extensively used in the development of biomaterials which can be used as tissue substitutes or can assist in tissue regeneration. Before commercialisation is allowed all biomaterials must prove to be functional and suitable for clinical use. Therefore, the evaluation of biomaterials requires rigorous and relevant testing. Biomaterials must be able to perform with an appropriate host response in a specific application. Tests must provide information to understand the host response, long-term outcome and issues pertaining to these. In the research reported in this thesis, an acellular porcine derived cross-linked collagen-based biomaterial (Permacol surgical implant) was analysed with a wide range of evaluation and compared to acellular noncross-linked and cellular, naturally cross-linked, equivalents. These matrices were characterized relating to their structure, composition and mechanical and biochemical properties. In addition, biological characterisation was performed through several studies designed to evaluate and compare biological responses in vitro, as well as in situ assessment of biocompatibility and effectiveness as a repair material and as bulking tissue. Permacol surgical implant was shown to be biocompatible, effective and efficient when used as bulking tissue and for soft tissue repair; furthermore, this biomaterial was resistant to enzymatic digestion and tolerant to bacterial presence suggesting that it could be used in some complicated clinical situations.

No description available.

The aims of this study were to prepare poly (ethylcyanoacrylate) (PECA) nanoparticles on the basis of different types of microemulsions, to investigate the entrapment within and release of a bioactive from these particles and to establish a set of delivery systems with varying entrapment and release characteristics, thereby giving the formulator the opportunity of a more tailor-made approach in the development of a delivery system. Furthermore the scale up of particle preparation and the possible enhancement of the immunogenic properties of PECA particles by incorporation of the adjuvant Quil A was investigated. Methods: Four phase triangles were established and microemulsion samples, used as a template to prepare nanoparticles, were characterised by viscosity and conductivity measurements, polarising light microscopy, freeze fracture transmission electron microscopy (TEM), cryo field emission electron microscopy (cryo FESEM) and self-diffusion NMR to determine their microemulsion type (droplet, bicontinuous, solution type). PECA nanoparticles were prepared from different types of microemulsions by interfacial polymerisation. Particle size, polydispersity index (PI) and [zeta]-potential were measured by photon correlation spectroscopy and electrophoretic mobility respectively. Normal scanning electron microscopy (SEM) and cryo FESEM were used to visualise particles. Fluorescently labelled ovalbumin (FITC-OVA) was used as a model protein/antigen and entrapment within and release from nanoparticles was investigated. To scale up nanoparticle preparation an instrumental set-up with reactor, peristaltic pump and stirrer was used. A 2⁷ fractional factorial study was designed to observe possible factors or their interactions that could influence particle formation under scale up conditions. For an immunological study freeze dried formulations of PECA nanoparticles, having FITC-OVA and Quil A entrapped, were prepared, and activation and uptake of formulations by murine bone marrow derived dendritic cells (DCs) and T cells in vitro were monitored. Results: Results obtained from the measurements described above, for formulations from the four different phase triangles, indicated that microemulsions of w/o droplet, bicontinuous or solution type could be formed. It was possible to prepare PECA nanoparticles from all of the different types of microemulsions. Particles had an average size of 265 nm � 24, with an average PI of 0.18 � 0.05 and an average negative [zeta]-potential of -17 mV � -5. Particle size, PI and [zeta]-potential were not influenced by the type of microemulsion that was used as a polymerisation template. Entrapment and release were however influenced by the type of microemulsion and although entrapment of FITC-OVA was generally high for PECA particles, it was highest for particles prepared from a droplet type microemulsion. Entrapment could also be increased by increasing amounts of monomer. The rate of release was dependent on the amount of monomer used for polymerisation and the type of microemulsion used for particle preparation, with nanoparticles prepared from a w/o droplet type microemulsion showing the slowest release. Furthermore it was shown that particle preparation could be scaled-up with the instrumental set-up used in this study, but conditions need to be refined as the average particle size and polydispersity index were considerably larger (441 nm � 101, 0.68 � 0.14) when compared to particles prepared by the beaker-pipette method (see above). The adjuvant Quil A could efficiently be entrapped into PECA nanoparticles together with FITC-OVA. Incubation of DCs and T cells with the various formulations did, however, not result in increased uptake or activation. Conclusions: PECA nanoparticles with high entrapment efficiency of antigen and adjuvant can be prepared from different types of microemulsions. Particles show different rates of entrapment and release depending on the type of microemulsion used as a polymerisation template, possibly because two different types of nanoparticles form. Nanocapsules are believed to form on the basis of droplet type microemulsions and nanospheres form on the basis of bicontinuous and solution type microemulsions. Freeze dried formulations of PECA nanoparticles, containing Quil A and FITC-OVA, were not able to induce an immune response, which might be due to charge repulsion effects between the negatively charged PECA nanoparticles and the negatively charged surface of dendritic cells. Moreover, no adjuvant effect of Quil A was apparent, perhaps caused by total encapsulation of the compound into the particle matrix with no active groups extending out displaying adjuvanticity.

Doctor of Philosophy(PhD) / Biomedical materials are being extensively researched, and many different types such as metals, metal alloys, and polymers are being used. Currently used biomedical materials are not perfect in terms of corrosion resistance, biocompatibility, and surface properties. It is not easy to fabricate from scratch new materials that can fulfill all requirements and an alternative approach is to modify the surface properties of current materials to cater to the requirements. Plasma immersion ion implantation (PIII) is an effective and economical surface treatment technique and that can be used to enhance the surface properties of biomaterials. The unique advantage of plasma modification is that the surface properties and functionalities can be enhanced selectively while the favorable bulk attributes of the materials such as strength remain unchanged. In addition, the non-line of sight feature of PIII is appropriate for biomedical devices with complex geometries such as orthopedic implants. However, care must be exercised during the plasma treatment because low-temperature treatment is necessary for heat-sensitive materials such as polymers which typically have a low melting point and glass transition temperature. Two kinds of biomedical materials will be discussed in this thesis. One is nickel titanium (NiTi) alloy which is a promising orthopedic implant material due to its unique shape memory and superelastic properties. However, harmful ions may diffuse from the surface causing safety hazards. In this study, we investigate the properties and performance of NiTi after nitrogen and oxygen PIII in terms of the chemical composition, corrosion resistance, and biocompatibility. The XPS results show that barrier layers mainly containing TiN and TiOx are produced after nitrogen and oxygen PIII, respectively. Based on the simulated in vitro and electrochemical corrosion tests, greatly reduced ion leaching and improved corrosion resistance are accomplished by PIII. Porous NiTi is also studied because the porous structure possesses better bone ingrowth capability and compatible elastic modulus with human bones. These advantages promote better recovery in patients. However, higher risks of Ni leaching are expected due to the increased exposed surface area and rougher topography than dense and smooth finished NiTi. We successfully apply PIII to porous NiTi and in vitro tests confirm good cytocompatibility of the materials. The other type of biomedical materials studied here is ultra-high molecular weight polyethylene (UHMWPE) which is a potential material for use in immunoassay plates and biosensors. In these applications, active antibodies or enzymes attached to a surface to detect molecules of interests by means of specific interactions are required. Moreover, the retention of enzyme activity is crucial in these applications. Therefore, the aim of this study is to investigate the use of PIII to prepare UHMWPE surfaces for binding of active proteins in terms of the binding density and ‘shelf life’ of the treated surfaces. Argon and nitrogen PIII treatments are attempted to modify the surface of UHMWPE. Horseradish peroxidase (HRP) is selected to conduct the protein binding test since it is a convenient protein to assay. Experimental results show that both PIII treated surfaces significantly improve the density of active HRP bound to the surface after incubation in buffer containing HRP. Furthermore, the PIII treated surfaces are found to perform better than a commercially available protein binding surface and the shelf life of the PIII treated surfaces under ambient conditions is at least six months. In conclusion, a biocompatible barrier layer on NiTi and a protein binding surface on UHMWPE is synthesized by PIII. The surface properties such as corrosion resistance and functionality on these two different types of substrates are improved by PIII.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 235-253) Also available in print.

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Barker, Thomas; Committee Member: Murthy, Niren; Committee Member: Roman, Jesse

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

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Wang, Yadong; Committee Member: Barker, Thomas; Committee Member: Boyan, Barbara; Committee Member: Chaikof, Elliot; Committee Member: Meredith, J. Carson; Committee Member: Prausnitz, Mark.