VEGF with AMD3100 Endogenously Mobilizes Mesenchymal Stem Cells and Improves Fracture Healing

A significant number of fractures develop non‐union. Mesenchymal stem cell (MSC) therapy may be beneficial, however, this requires cell acquisition, culture and delivery. Endogenous mobilization of stem cells offers a non‐invasive alternative. The hypothesis was administration of VEGF and the CXCR4 antagonist AMD3100 would increase the circulating pool of available MSCs and improve fracture healing. Ex‐breeder female wistar rats received VEGF followed by AMD3100, or sham PBS. Blood prepared for culture and colonies were counted. P3 cells were analyzed by flow cytometry, bi‐differentiation. The effect of mobilization on fracture healing was evaluated with 1.5 mm femoral osteotomy stabilized with an external fixator in 12–14 week old female Wistars. The mobilized group had significantly greater number of cfus/ml compared to controls, p = 0.029. The isolated cells expressed 1.8% CD34, 35% CD45, 61% CD29, 78% CD90, and differentiated into osteoblasts but not into adipocytes. The fracture gap in animals treated with VEGF and AMD3100 showed increased bone volume; 5.22 ± 1.7 µm3 and trabecular thickness 0.05 ± 0.01 µm compared with control animals (4.3 ± 3.1 µm3, 0.04 ± 0.01 µm, respectively). Radiographic scores quantifying fracture healing (RUST) showed that the animals in the mobilization group had a higher healing score compared to controls (9.6 vs. 7.7). Histologically, mobilization resulted in significantly lower group variability in bone formation (p = 0.032) and greater amounts of bone and less fibrous tissue than the control group. Clinical significance: This pre‐clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non‐union fractures

Fixation of uncemented implants

My thesis postulates that bone ingrowth and direct bone apposition combined with implants engineered to produce interfacial strains lead to beneficial bone remodelling which may result in fixation of joints that will last for the patients life-time. The concept of extra-cortical plate fixation was investigated by assessing the bony response to plates of different design and surface coating. The study found that only one geometric design (holes) significantly increased bone ingrowth into the plate when compared with the control (p=0.01). A crystalline HA coating encouraged significantly greater interfacial contact when compared with a roughened titanium surface (p=0.01), a HA coating of lower crystallinity (p=0.004) and a solution precipitated HA coating (p=0.02). No significant differences were found when bone ingrowth into the plates were compared, except significantly more bone had grown into plates coated with a HA coating of lower crystallinity (p=0.036). Differences in bony reaction induced by the plates of different design were evident and therefore a combination of the correct design and surface coating are required for optimal bone attachment and ingrowth to extra-cortical plates. An experimental goat model was developed to investigate hydroxyapatite coated extra-cortical plate fixation in massive segmental bone tumour replacements. On retrieval, all of the plates were securely fixed by new bone. Bone apposition had occurred through a combination of periosteal bone production, invasion of bone through slots and bone growth over the ends of the plate. It was concluded that due to both mechanical and biological effects, extra-cortical plate fixation generated new bone growth that enhanced fixation and encouraged plate integration into cortical bone. The importance of the implant surface was demonstrated in a series of human autopsy retrieved hip implants. The proximal region of each implant was coated with either a plasma sprayed porous ingrowth surface (plain porous), a HA coated porous surface (porous HA) or a grit blasted surface. Significantly more bone ingrowth (p=0.012) and bone attachment (p<0.05) was measured to the porous HA surface when compared with the plain porous surface. There was no significant difference in bone attachment between the plain porous and grit blasted surfaces. A combination of a HA surface combined with extra-cortical plate fixation has been used to treat a number of bone tumour patients

Exploration of dietary patterns and alcohol consumption in pregnant women in the UK: A mixed methods study

Backgroundfetal Alcohol Spectrum Disorders is a term used to describe a range of physical, cognitive and behavioural deficits in the offspring of women who drank alcohol during pregnancy. A growing body of evidence suggests alcohol consumption in the presence of poor maternal nutrition may increase the risk of harm to the developing fetus.Objectiveto investigate relationships between maternal dietary patterns and alcohol consumption, and explore which factors influence women's decisions about what to eat and drink during pregnancy.Designa mixed methods study comprising a questionnaire (paper-based and online) and semi-structured, in-depth interviews with a sub-sample of women who completed the questionnaire.Participantswomen were eligible for inclusion if they were ≥16 years of age, pregnant and living in the UK and were recruited through antenatal clinics, specialist substance misuse antenatal clinics or via social media platforms; 350 women completed a questionnaire and a sub-sample of 6 women participated in an interview.Methodsthe questionnaire comprised the Alcohol Use Disorders Identification Test Consumption to measure alcohol consumption patterns and a Food Frequency Questionnaire to measure dietary intake. Dietary pattern analysis was conducted using Principle Components Analysis and linear regression models were used to explore relationships between dietary pattern scores and alcohol consumption. Analyses were adjusted for socio-demographic and lifestyle characteristics. Semi-structured, in-depth interviews were conducted face-to-face and analysed thematically.Findingstwo key dietary patterns were derived. Women who reported frequent alcohol consumption before and during pregnancy were more likely to adhere to the ‘Prudent’ dietary pattern compared to those who abstained. No relationships were observed between alcohol consumption and adherence to the ‘Cafeteria’ dietary pattern. Six key themes were identified through the qualitative analysis: (1) pregnancy as a time to review behaviour; (2) listen to your body – it will tell you what you need; (3) treats are still important – on special occasions; (4) social and cultural expectations constrain behaviour; (5) inconsistent or ambiguous information creates uncertainty; and 6) confidence increases following a successful pregnancy.Conclusionsthose who drink low levels of alcohol during pregnancy may have better quality diets compared to women who report no alcohol consumption. The reasons for this are complex and influenced by social context and previous pregnancy experience, which should be considered when healthcare professionals provide advice during this period

The growth of non-c-axis-oriented ferroelectric BLT thin films on silicon using ZnO buffer layer

Lanthanum-doped bismuth titanate (BLT) thin films were grown on buffered Si substrates using a RF magnetron sputtering system. Electrically conducting ZnO layers were used as an effective buffer layer to facilitate the growth of the ferroelectric thin films. X-ray diffraction data shows the Aurivilius phase structure with the highest diffraction peak (1 1 7), indicating non-c-axis-oriented microstructure. Random oriented plate-like grains were observed using scanning electron microscopy. The ferroelectric nature of the film was proved by ferroelectric domain switching under an electrical field

Mechanisms of Bone Loss in Space

The unique conditions of microgravity and radiation exposure in space have a substantial impact on human tissue function, resulting in extreme bone loss. The goal of this project is to synthesize the current knowledge on bone loss in space for use in future research. There is clear evidence, based on past research, that microgravity, cosmic radiation, fluid flow, and mechanotransduction influence bone function during space travel and result in significant loss. However, there is a need for future research on how these factors relate to each other and their collective influence on mechanisms of bone regeneration and repair. In addition, there is a need for more research on potential solutions to prevent the bone loss seen during space travel

Partial Bone Formation in Additive Manufactured Porous Implants Reduces Predicted Stress and Danger of Fatigue Failure

New porous implant designs made possible by additive manufacturing allow for increased osseointegration, potentially improving implant performance and longevity for patients that require massive bone implants. The aim of this study was to evaluate how implantation and the strain distribution in the implant affect the pattern of bone ingrowth and how changes in tissue density within the pores alter the stresses in implants. The hypothesis was that porous metal implants are susceptible to fatigue failure, and that this reduces as osteointegration occurs. A phenomenological, finite element analysis (FEA) bone remodelling model was used to predict partial bone formation for two porous (pore sizes of 700 μm and 1500 μm), laser sintered Ti_{6}Al_{4}V implants in an ovine condylar defect model, and was compared and verified against in vivo, histology results. The FEA models predicted partial bone formation within the porous implants, but over-estimated the amount of bone-surface area compared to histology results. The stress and strain in the implant and adjacent tissues were assessed before, during bone remodelling, and at equilibrium. Results showed that partial bone formation improves the stress distribution locally by reducing stress concentrations for both pore sizes, by at least 20%. This improves the long-term fatigue resistance for the larger pore implant, as excessively high stress is reduced to safer levels (86% of fatigue strength) as bone forms. The stress distribution only changed slightly in regions without bone growth. As the extent of bone formation into extensively porous bone implants depends on the level of stress shielding, the design of the implant and stiffness have significant influence on bone integration and need to be considered carefully to ensure the safety of implants with substantial porous regions. To our knowledge this is the first time that the effect of bone formation on stress distribution within a porous implant has been described and characterised