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Hypohydration occurs voluntarily and involuntarily in exercising and occupational situations, thus replacement of fluid losses is essential to optimise recovery. The experiments in the present thesis have confirmed and extended previous research concerning the effects of different methods of moderate body water losses on exercise capacity and post-dehydration recovery of fluid deficits. It was confirmed that sweat sodium concentration, determined by a whole body wash- down technique, decreased during 7 consecutive days of exercise in the heat, though increased sweat rates resulted in identical daily sweat sodium losses over the 7 days. Fluid restriction over a 37h period induced an average 2.7% body mass loss, resulting in significant hypovolaemia and hypertonicity. Hypohydration was associated with increased reported thirst, tiredness, head soreness and impaired alertness and concentration. Evidence from the present thesis found that high intensity aerobic exercise capacity in a temperate environment is reduced by moderate hypohydration. Furthermore, hypohydration induced by combined exercise and fluid restriction reduced exercise capacity to a greater extent than fluid restriction alone. Body mass losses incurred by either 24h fluid restriction or combined fluid restriction/exercise resulted in 2% of body mass loss. Subsequent rehydration resulted in identical urine volumes being produced, drink retention and hence overall net fluid balance on both trials. Rapid recovery of fluid losses is recommended following hypohydration to re- establish exercise capacity. However present results suggest that this may have negative consequences for retention of a carbohydrate-electrolyte solution as a consequence of greater hypotonicity and hypervolaemia. Milk has been shown to be an effective fluid for post exercise rehydration and is a convenient means for creatine delivery. Ingestion of a milk based creatine containing drink was found to have a negative influence on recovery of fluid following exercise compared with a placebo, yet was seen to result in improved capacity for endurance exercise.

A three-dimensional computational human body model, named CHRIS (<b>C</b>omputational <b>H</b>uman <b>R</b>igid-Body <b>I</b>mpact <b>S</b>imulator), was developed to study the mechanical behaviour of the body in low and high acceleration environments. CHRIS is constructed from 15 rigid ellipses, which are connected by 14 kinematic joints, and has 34 degrees of freedom (DOF). Various human limbs and joints can be attached to CHRIS, so as to determine stresses and strains in specific body regions during impacts. Within this thesis a three-dimensional knee joint and lower leg are connected to CHRIS, and the stresses within the ligaments and bones are analysed. Biological materials, present within the human body, generally consist of an elastin ground substance and bundles of collagen fibres. Subsequently, hyperelastic transversely isotropic constitutive models are employed in this thesis. Bone is modelled using a general transversely isotropic hyperelastic function, which recovers the linear transversely isotropic constitutive matrix in the linear regime. Soft biological materials, such as tendons and ligaments, exhibit a high degree of stiffening for lower strains; thus, an exponential based function is used to stimulate this phenomenon. Although, soft biomaterials fundamentally display viscoelastic material properties, the time-dependent effects can be neglected when studying short impacts; hence, a purely hyperelastic response is sufficient. In the future, it is hoped that this research will prove to be a valuable tool in the automobile and aerospace industries, where the ability to predict injuries within the human body (and thus design safety systems) would be of use.

Previous studies have shown that increased bone growth over massive prosthesis, promoted by hydroxyapatite (HA)-coated collars, can reduce aseptic loosening. Bone tissue engineering techniques using bone marrow stromal cells (BMSCs) may be able to further enhance bone growth and fixation of implants to host bone. The hypothesis of this study was that BMSCs could enhance bone growth and bone-implant contact around bone tumour replacements. Two sources of bone marrow stem cells were firstly investigated, including those isolated directly from ovine bone marrow (BMSCs), and those isolated from ovine peripheral blood (peripheral blood-derived bone marrow stromal-like cells, or PBSCs). PBSCs were isolated after mobilisation via induced blood loss, or treatment with granulocyte-colony stimulating factor (G-CSF). BMSCs and PBSCs were characterised in vitro. A significant increase of fibroblastic colony-forming units (CFU-F) post-G-CSF treatment was observed only after white blood cell counts returned to normal levels, suggesting a possible steady-state balance between haematopoietic stem cells and BMSCs. Ovine BMSCs (oBMSCs), were found to survive and proliferate in fibrin glue or pressurised spray application. An in vivo mid-shaft tibial replacement model was then used to test the effect of autologous oBMSCs in fibrin glue on bone growth and bone-implant contact, when sprayed onto the HA-coated collars, compared to non-treated implants. Radiography showed that the oBMSCs more than doubled the amount of bone growth around the collars of the implants after six months (p=0.017 in the ML view, and p=0.05 in the AP view). Using histological techniques it was shown that bone area was significantly increased (p=0.02). Application of oBMSCs also reduced the radiolucent lines present between the new bone and implants, and improved bone-implant contact. This study demonstrated the potential of BMSCs to augment bone growth and bone-implant contact in conjunction with massive implants. The second in vivo study investigated the effect of BMSC cell dosage and use of allogeneic cells on new bone formation and bone-implant contact in a tibial transcortical pin model in sheep. Partially-HA-coated screws were sprayed with varying concentrations of autologous and allogeneic oBMSCs suspended in fibrin glue, and implanted. After six weeks, no significant difference in bone formation around the pins was found between groups (p>0.05), although the untreated group with HA coating-only had a significant increase in bone formation (p=0.03) compared to the other groups. In conclusion, this project has shown that ovine multipotent BMSCs and PBSCs can be isolated and expanded. When sprayed onto the HA-coated collars of massive implants, BMSCs can augment bone formation and bone-implant contact. However, another model spraying oBMSCs onto trans-cortical pins did not produce a significant increase in bone growth or bone-implant contact. The findings presented may have important clinical applications in the use of BMSCs to reduce aseptic loosening, which may improve the survival of massive implants.

Bioresorbable polymers, especially the homo and co-polymers of poly lactic acid (PLA) and poly glycolic acid (PGA), have been used for a broad range of applications for the last three decades owing to their biodegradable, biocompatible and non-toxic natures. One of the applications for these polymers is in the orthopaedic surgery as bone fixation device. According to the Wolff‟s law, if the bone fixation devices are overly strong to shield the healing bone from sufficient stress stimulation, the bone will resorb to an extent. Therefore the optimised design of such devices relies on the prediction of the stress redistribution between the device and the bone during the device degradation. However, the auto-catalysis nature of the polymer degradation brings extra complications to the modelling of the device degradation. Currently the time consuming trial and error approach is widely employed in the device development. In fact mathematical models and the finite element method can be a great assistance to the designing of these resorbable devices. This thesis presents a complete model for the interaction between a resorbable fixation device and a healing bone. A phenomenological model is firstly presented that can capture the main features of the polymer degradation. An important factor in this model is the effective diffusion coefficient for the oligmers which is studied subsequently. Then an entropy theory based model is presented to relate the decay of Young‟s modulus to the polymer degradation. Finally the polymer degradation model and the Young‟s modulus decay model is integrated with a bone remodelling model and stress analysis to predict the growth or decay of a healing bone that is “protected” by a bioresorbable fixation device. The work in this thesis focuses on amorphous polymers. The work is entirely computational which is guided by existing experimental data and observations in the literature.