Papers by Author: Y. Yu

Abstract: Protein expression of growth factors involved in fracture healing and osteoporosis were investigated in ovariectomised (OVX) rat fracture model using histological and immunohistochemical analysis. The OVX model was confirmed by a significantly increased body weight and reduced bone density of the non-fracture hind limbs. The tissue morphology and the protein expression were assessed on the paraffin sections of the fracture callus at day 7, 14, 28 and 42 after fracture. Histology revealed a significantly higher ratio of fibrous tissue over bone or cartilage over bone in the fracture callus at day 28 and 42 in the OVX rats than in the normal rats. Immunohistochemical staining of IGF-I, IGF-IRα, MMP-1, TIMP-1 and 2 showed a different pattern between the OVX and the control groups. A down-regulation of IGF-I and TIMP-1 and an up-regulation of MMP-1 were observed in OVX rats, which may account in part for the delayed healing of the osteoporotic fracture and may affect extracellular matrix composition, an important determinant of callus strength.

Abstract: The number of peri-prosthetic femoral fractures in todays aging population is increasing. Fractures of the femur may occur intra-operatively or post-operatively, either at the tip of the femoral stem or in areas where cortical thinning has occurred. This is further enhanced if the patient is osteoporotic. These fractures can be difficult to treat due to the complexity of the mechanical status and further complicated biologically by the presence of ultra high molecular weight polyethylene (UHMWPE) wear debris that can migrate from the articulating surface of the prosthesis to the fracture site. In this study, the effect of PE wear debris on the healing of osteoporotic fractures was investigated using a rodent ovariectomised (OVX) model. One hundred female Sprague Dawley rats were subjected to either bilateral OVX or Sham surgery at 10 weeks of age. Three months later, a closed fracture was created in the right femur using a 3-point bending device and an intramedullary k-wire for fixation. Animals were divided into 4 groups (n=3-8). A 0.2ml suspension of Ceridust (PE wear debris), hyaluronic acid & saline was injected directly into the fracture site at the time of surgery into half the animals. Control animals received comparable injections excluding the Ceridust. Animals were sacrificed at 1, 3 and 6 weeks. The OVX animals had a greater body weight compared to the Sham animals (p<0.05). DEXA analysis revealed that the presence of PE wear debris had no effect on the BMD within the fracture callus at either time-point. Mechanical analysis revealed an increase in bone strength with time. The presence of PE had no statistical effect upon the ultimate peak load or stiffness, however there was a trend towards increased peak load in the PE groups at 3 and 6 weeks following 3-months oestrogen deficiency. Histological analysis showed that the control OVX fractures had more cartilage development than the Sham group at 3 weeks and delayed remodeling at 6 weeks. The PE treated OVX group showed more fibrous tissue at the fracture gap and inside the diaphysis tunnel showing further delayed healing compared to the Sham group with PE. In this study after 3-months of oestrogen deficiency, no differences in mechanical or BMD was found in the fractured limbs between the PE –treated and non-PE treated fractures. However, histologically, PE wear debris induced fibrous tissue at the fracture site which further delayed the healing process. More care should be taken with aged patients receiving revision surgery, as these patients become harder to manage when fractured due to the influence of both osteoporosis and PE wear debris.

Abstract: Deep-frozen morselized human bone grafts showed osteoconductivity and osteoinductivity when implanted into tibial window defects of nude rats. The osteoconductivity was assessed by measuring the total area of newly formed bone bridged by the implanted bone grafts in the entire defect area. The osteoinductivity was evidenced by the presence of active osteoblast-like cells and new bone formation around the implanted bone grafts, which were surrounded by soft tissues distant from the host cortex. Gamma irradiation at the doses of 15 or 25 kGray reduced the osteoconductivity (ANOVA and LSD tests, p<0.05) at 3 weeks post operation. The 25 kGray group had a significantly lower level of new bone formation compared with the 0 and 15 kGray groups. The evidences of osteoinductivity were only noted in the 0 and 15 kGray groups. Our data indicate that 25 kGray gamma irradiation reduces the osteoconductive and osteoinductive properties of the morselized human bone graft.