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Silane modification has been proposed as a powerful biomaterial surface modification tool. This is the first comprehensive investigation into the effect of silane chain length on the resultant properties of –NH2 silane monolayers and the associated osteoinductive properties of the surface. A range of –NH2 presenting silanes, chain length 3–11, were introduced to glass coverslips and characterized using water contact angles, atomic force microscopy, X‐ray photoelectron spectroscopy, and Ninhydrin assays. The ability of the variation in chain length to form a homogenous layer across the entirety of the surfaces was also assessed. The osteoinductive potential of the resultant surfaces was evaluated by real‐time polymerase chain reaction, immunocytochemistry, and von Kossa staining. Control of surface chemistry and topography was directly associated with changes in chain length. This resulted in the identification of a specific, chain length 11 (CL11) which significantly increased the osteoinductive properties of the modified materials. Only CL11 surfaces had a highly regular nano‐topography/roughness which resulted in the formation of an appetite‐like layer on the surface that induced a significantly enhanced osteoinductive response (increased expression of osteocalcin, CBFA1, sclerostin, and the production of a calcified matrix) across the entirety of the surface. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1862–1877, 2018.

Non-union fractures are defined as fractures that do not heal after 6 months of conventional treatment. They usually require multiple surgical treatments, autologous bone grafts or treatments with growth factors or Bone morphogenetic proteins (BMPs). There is a clinical need for a material which can be used to replace autologous bone transplantation in the treatment non-union fractures that negates the problems associated with autologous grafts. This thesis aims to consider and develop a coating that can be used on a readily available polymer biomaterial to induce a response from mesenchymal stem cells, which are found in abundance at fracture sites, and facilitate repair by their differentiation into osteogenic cells. The use of a synthetic chemical coating rather than a growth factor or peptide aims to cause similar effects at a greatly reduced cost Plasma application techniques were used initially to screen potential terminal groups on a 3D system. Amine groups were found to be osteogenic (which was confirmed by positive Von Kossa and Alizarin red staining), and hydroxyl groups were found to be chondrocytic (which was confirmed by positive Van Geison and Alcian blue staining). The osteogenic effect of the amine group was investigated further, but in the form of silane SAMs, which were more easily definable. The presentation of the terminal group was investigated using varying carbon chain length, to see if this had an effect on osteogenicity) This was explored using both MSC and primary osteoblast-like cell models on glass initially, then on PLGA films and finally a 3D PLGA system. The results of this showed positive expression of osteogenic markers for the MSC and osteoblast-like cells when on glass and PLGA films. There was an expression of the osteogenic marker osteocalcin and a positive mineralisation stain (Von Kossa) at 7 days. This effect however was not transferred to a 3D platform as further optimisation will be required to achieve this goal-an essential progression on the way to the development of an injectable 3D system suitable for clinical application.

The metabolism and excretion of [ring-U-[14]C]DDT, [ring-U-[14]C]DDD, [ring-U-14 C]DDE and [ring-U-[14]C]DDMU in male rats and male Japanese quail were investigated following intraperitoneal administration of these compounds. The radioactivity excreted daily was monitored and the following estimations were made of the time taken to excrete half of the radioactive dose; 12.1 days and 47.7 days for [14 C]DDT-dosed rats and quail, days and 21.3 days for [14 C]DDD-dosed rats and quail, 23.7 days and 128.9 days for [[14]C]DDE-dosed rats and quail, 6.4 days and 4.3 days for [[14]C]DDMU-dosed rats and quail respectively. More of the dose was excreted as unchanged compound by the quail except when [[14]C]DDMU was administered. [[14]C]DDA, free or conjugated, was the major metabolite excreted by rats after dosing with each of the test compounds, with DDT and DBMU giving rise to the most [[14]C]DDA. In the quail, DDD resulted in greatest DDA production but only a very little DDA was excreted after DDMU administration. [[14]C] DDOH was detected as a metabolite of both [[14]C]DDT and [[14]C]DDMU in rats but only of [[14]C]DDMU in quail. DBP was tentatively identified in animal excreta in every dose group except the DDT-dosed quail. [[14]C]DDD and [[14]C]DDE were metabolites of [[14]C]DDT in both rats and quail and [14 C]DDE was also a metabolite of [[14]C]DDD in both species. Two [[14]C] hydroxylated derivatives were also detected; HO-DDE from DDE in rats and HO-DDMU from DDMU in quail. The major metabolite of DDMU in quail was not conclusively identified. Kovel metabolic pathways for the metabolism of DDT in rats and quail are proposed. The rat may convert DDT to DDA by at least two routes only one of which includes DDD. DDD and DDE are both converted to DDA but the pathway does not include DDMU. DDMU can be metabolised to DDOH and DDA. DBP is probably produced directly from DDT, DDD, DDE and DDMU. In the quail similar routes appear to operate except that DDT is probably metabolised to DDA via DDD, while DDMU is mainly metabolised to DDOH and DBP cannot be produced from DDT.