Kalia, P.; (2007) Enhancing the fixation of massive implants using bone marrow stromal cells. Doctoral thesis , University of London.

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Abstract

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.

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