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Abstract
Segmental gap defects in long bones are amongst the most difficult to heal. Membrane guided bone regeneration is a type of guided tissue regeneration wherein the gap defect is contained within a membrane – usually semi-permeable. The aim of this thesis was to establish a reproducible cross-species model and to investigate the nature of membrane guided bone regeneration in detail. In a sheep tibia model, using reinforced ePTFE (expanded poly-tetra-fluoro-ethylene) tubes, critical 2.5 cm gap defects healed in 13/13 sheep compared with healing in only 2/11 in the control group (p<0.05). Radiographic features in the ePTFE group included a horseshoe shaped endosteal regenerate, and postero-lateral periosteal regenerate. DEXA analysis demonstrated significantly larger area of bone formation in the membrane group (p<0.05). Overall bone mineral density was also better in the membrane group (p<0.05). Angiography showed 57 % vascularity posteriorly in the gap region compared to 43 % anteriorly (p=0.01) and 1.8 vessels /cm2 in the membrane group compared to 1.3 vessels/cm2 in the controls (p=0.01). Microscopy demonstrated new bone formation both within and outside the membrane. Periosteal bone was denser and mature while endosteal new bone was woven in nature, interspersed with cartilage islands. The collagen pattern observed in phase contrast microscopy indicated the endosteal new bone to be in continuity with the cambium layer of the cortex. These findings were reproduced in a rabbit forearm model, with union in 20/20 membrane specimens and non-union in 20/20 controls. In human subjects, using a meshed periosteal autograft, as a bioactive membrane, to contain cancellous autograft, union was obtained in 9/9 recalcitrant non-unions, including seven cases of congenital pseudoarthrosis of the tibia.