An evaluation of clinical procedures used in dental implant treatment in posterior maxilla using flapless technique

This study was a measure forward in cultivating the scientific basis for an approach to examine clinical procedure in Flapless dental implant surgery. The thesis is based on: the systematic review, retrospective study of flapless implants, and in vivo study on the osseo-integration in osteoporotic rats. Dr Doan investigated "clinical procedures used in dental implant treatment in posterior maxilla using flapless technique". The work has yielded significant contributions to the area of implant flapless surgery and its effects on osteoporotic patients having implants in the posterior maxilla.

Integrin-functionalized artificial membranes as test platforms for monitoring small integrin ligand binding by surface plasmon-enhanced fluorescence spectroscopy

The design and synthesis of molecularly or supramolecularly defined interfacial architectures have seen in recent years a remarkable growth of interest and scientific research activities for various reasons. On the one hand, it is generally believed that the construction of an interactive interface between the living world of cells, tissue, or whole organisms and the (inorganic or organic) materials world of technical devices such as implants or medical parts requires proper construction and structural (and functional) control of this organism–machine interface. It is still the very beginning of generating a better understanding of what is needed to make an organism tolerate implants, to guarantee bidirectional communication between microelectronic devices and living tissue, or to simply construct interactive biocompatibility of surfaces in general. This exhaustive book lucidly describes the design, synthesis, assembly and characterization, and bio-(medical) applications of interfacial layers on solid substrates with molecularly or supramolecularly controlled architectures. Experts in the field share their contributions that have been developed in recent years.

Multidirectional effects of Sr, Mg and Si-containing bioceramic coatings with high bonding strength on inflammation, osteoclastogenesis and osteogenesis

Ideal coating materials for implants should be able to induce excellent osseointegration, which requires several important parameters, such as good bonding strength, limited inflammatory reaction, balanced osteoclastogenesis and osteogenesis, to gain well-functioning coated implants with long-term life span after implantation. Bioactive elements, like Sr, Mg and Si, have been found to play important roles in regulating the biological responses. It is of great interest to combine bioactive elements for developing bioactive coatings on Ti-6Al-4V orthopedic implants to elicit multidirectional effects on the osseointegration. In this study, Sr, Mg and Si-containing bioactive Sr2MgSi2O7 (SMS) ceramic coatings on Ti-6Al-4V were successfully prepared by plasma-spray coating method. The prepared SMS coatings have significantly higher bonding strength (~37MPa) than conventional pure hydroxyapatite (HA) coatings (mostly in the range of 15-25 MPa). It was also found that the prepared SMS coatings switch the macrophage phenotype into M2 extreme, inhibiting the inflammatory reaction via the inhibition of Wnt5A/Ca2+ and Toll-like receptor (TLR) pathways of macrophages. In addition, the osteoclastic activities were also inhibited by SMS coatings. The expression of osteoclastogenesis related genes (RANKL and MCSF) in bone marrow derived mesenchymal cells (BMSCs) with the involvement of macrophages was decreased, while OPG expression was enhanced on SMS coatings compared to HA coatings, indicating that SMS coatings also downregulated the osteoclastogenesis. However, the osteogenic differentiation of BMSCs with the involvement of macrophages was comparable between SMS and HA coatings. Therefore, the prepared SMS coatings showed multidirectional effects, such as improving bonding strength, reducing inflammatory reaction and downregulating osteoclastic activities, but maintaining a comparable osteogenesis, as compared with HA coatings. The combination of bioactive elements of Sr, Mg and Si into bioceramic coatings can be a promising method to develop bioactive implants with multifunctional properties for orthopaedic application.

Bone regeneration based on tissue engineering conceptions – a 21st century perspective

The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate

The osteoimmunomodulatory property of bone biomaterials is a vital property determining the in vivo fate of the implants. Endowing bone biomaterials with favorable osteoimmunomodulatory properties is of great importance in triggering desired immune response and thus supports the bone healing process. Magnesium (Mg) has been recognized as a revolutionary metal for applications in orthopedics due to it being biodegradable, biocompatible, and having osteoconductive properties. However, Mg's high rate of degradation leads to an excessive inflammatory response and this has restricted its application in bone tissue engineering. In this study, β-tricalcium phosphate (β-TCP) was used to coat Mg scaffolds in an effort to modulate the detrimental osteoimmunomodulatory properties of Mg scaffolds, due to the reported favorable osteoimmunomodulatory properties of β-TCP. It was noted that macrophages switched to the M2 extreme phenotype in response to the Mg-β-TCP scaffolds, which could be due to the inhibition of the toll like receptor (TLR) signaling pathway. VEGF and BMP2 were significantly upregulated in the macrophages exposed to Mg-β-TCP scaffolds, indicating pro-osteogenic properties of macrophages in β-TCP modified Mg scaffolds. This was further demonstrated by the macrophage-mediated osteogenic differentiation of bone marrow stromal cells (BMSCs). When BMSCs were stimulated by conditioned medium from macrophages cultured on Mg-β-TCP scaffolds, osteogenic differentiation of BMSCs was significantly enhanced; whereas osteoclastogenesis was inhibited, as indicated by the downregualtion of MCSF, TRAP and inhibition of the RANKL/RANK system. These findings suggest that β-TCP coating of Mg scaffolds can modulate the scaffold's osteoimmunomodulatory properties, shift the immune microenvironment towards one that favors osteogenesis over osteoclastogenesis. Endowing bone biomaterials with favorable osteoimmunomodulatory properties can be a highly valuable strategy for the development or modification of advanced bone biomaterials.

Integrated plasma-aided nanofabrication facility: Operation, parameters, and assembly of quantum structures and functional nanomaterials

The development, operation, and applications of two configurations of an integrated plasma-aided nanofabrication facility (IPANF) comprising low-frequency inductively coupled plasma-assisted, low-pressure, multiple-target RF magnetron sputtering plasma source, are reported. The two configurations of the plasma source have different arrangements of the RF inductive coil: a conventional external flat spiral "pancake" coil and an in-house developed internal antenna comprising two orthogonal RF current sheets. The internal antenna configuration generates a "unidirectional" RF current that deeply penetrates into the plasma bulk and results in an excellent uniformity of the plasma over large areas and volumes. The IPANF has been employed for various applications, including low-temperature plasma-enhanced chemical vapor deposition of vertically aligned single-crystalline carbon nanotips, growth of ultra-high aspect ratio semiconductor nanowires, assembly of optoelectronically important Si, SiC, and Al1-xInxN quantum dots, and plasma-based synthesis of bioactive hydroxyapatite for orthopedic implants.

RF plasma sputtering deposition of hydroxyapatite bioceramics : synthesis, performance, and biocompatibility

Hydroxyapatite (HA) coatings have numerous applications in orthopedics and dentistry, owing to their excellent ability to promote stronger implant fixation and faster bone tissue ingrowth and remodeling. Thermal plasma spray and other plasma-assisted techniques have recently been used to synthesize various calcium phosphate-based bioceramics. Despite notable recent achievements in the desired stoichiometry, phase composition, mechanical, structural, and bio-compatible properties, it is rather difficult to combine all of the above features in a single coating. For example, many existing plasma-sprayed HA coatings fall short in meeting the requirements of grain size and crystallinity, and as such are subject to enhanced resorption in body fluid. On the other hand, relatively poor interfacial bonding and stability is an obstacle to the application of the HA coatings in high load bearing Ti6Al4V knee joint implants. Here, we report on an alternative: a plasma-assisted, concurrent, sputtering deposition technique for high performance biocompatible HA coatings on Ti6Al4V implant alloy. The plasma-assisted RF magnetron co-sputtering deposition method allows one to simultaneously achieve most of the desired attributes of the biomimetic material and overcome the aforementioned problems. This article details the film synthesis process specifications, extensive analytical characterization of the material's properties, mechanical testing, simulated body fluid assessments, biocompatibility and cytocompatibility of the HA-coated Ti6Al4V orthopedic alloy. The means of optimization of the plasma and deposition process parameters to achieve the desired attributes and performance of the HA coating, as well as future challenges in clinical applications are also discussed.

Using patient specific finite element models to understand the biomechanics of paediatric spinal deformity surgery

Adolescent idiopathic scoliosis (AIS) is a spinal deformity, which may require surgical correction by attaching rods to the patient’s spine using screws inserted into the vertebrae. Complication rates for deformity correction surgery are unacceptably high. Determining an achievable correction without overloading the adjacent spinal tissues or implants requires an understanding of the mechanical interaction between these components. We have developed novel patient specific modelling software to create individualized finite element models (FEM) representing the thoracolumbar spine and ribcage of scoliosis patients. We are using these models to better understand the biomechanics of spinal deformity correction.

Role of microRNAs in improved osteogenicity of topographically modified titanium implant surfaces

This project aimed at understanding the molecular mechanisms involved in the superior integration of micro-roughened titanium implant surfaces with the surrounding bone, when compared with their smooth surfaces. It involved studying the role of microRNAs and cell signaling pathways in the molecular regulation of bone cells on topographically modified titanium dental implants. The findings suggest a highly regulated microRNA-mediated control of molecular mechanisms during the process of bone formation that may be responsible for the superior osseointegration properties on micro-roughened titanium implant surfaces and indicate the possibility of using microRNA modulators to enhance osseointegration in clinically demanding circumstances.

Investigating the effect of internal fixation stiffness on metaphyseal fracture healing in a mouse model

This project examined the differences in healing of metaphyseal bone, when the implants of variable stiffness are used for fracture fixation. This knowledge is important in development of novel orthopaedic implants, used in orthopaedic surgery to stabilise the fractures. Dr Koval used a mouse model to create a fracture, and then assessed its healing with a combination of mechanical testing, microcomputed tomography and histomorphometric examination.

Intravitreal drug delivery in retinal disease : are we out of our depth?

Introduction With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise. Areas covered We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally. Expert opinion Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully; however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.

Repeatability of static load bearing exercises during rehabilitation of individuals with transfemoral amputation fitted with osseointegrated implant

Bone-anchored prostheses, relying on implants to attach the prosthesis directly to the residual skeleton, are the ultimate resort for patients with transfemoral amputations (TFA) experiencing severe socket discomfort. The first patient receiving a bone-anchored prosthesis underwent the surgery in 1990 in the Sahlgrenska University Hospital (Sweden). To date, there are two commercially available implants: OPRA (Integrum, Sweden) and ILP (Orthodynamics, Germany). The key to success to this technique is a firm bone-implant bonding, depending on increasing mechanical stress applied daily during load bearing exercises (LBE). The loading data could be analysed through different biomechanical variables. The intra-tester reliability of these exercises will be presented here. Moreover the effect of increase of loading, axes of application of the load and body weight as well as the difference between force and moment variables will be discussed.

Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.