Infection and skin ulcer are major problems in Total Knee Arthroplasty (TKA) and Bipolar Hip Prosthesis (BHP). Sugar (sucrose) has been used for wound care in many countries because it absorbs fluid, stimulates granulation, and suppress growth of bacteria. Trafermin ∗∗∗∗∗ recombinant human basic fibroblast growth factor ∗∗∗∗∗ FGF ∗∗∗∗∗ accelerates granulation process and improves quality of wound healing. We have used sucrose and trafermin for treatment of infection after TKA and BHP. Six infected TKA with skin ulcer and one infected BHP with fistula were treated with Trafermin and sugar. TKA were performed in four osteoarthritis and two rheumatoid arthritis, and BHP was for femoral neck fracture. Implants were removed in three cases because of deep infection. One was male and six were female, average age were 60.8 years old ranged 43 to 77. Follow-up period were one to 5 years. Four cases were related to MRSA. Sugar treatment were performed for two to 23 weeks, and Trafermin was sprayed once a day for two to 16weeks. In BHP case, sugar therapy was performed intermittently. In two deep infected TKA cases, infection ceased in one to 4 month and revision TKA were performed. In other four TKA cases, infection were ceased in two to 16 weeks. In BHP case, fistula closed in three years. Combination of Trafermin and sugar is useful for management of infection and skin ulcer after TKA and BHP

Background. The process of osteolysis is well studied both in vivo and in vitro. Although multiple pathways have been implicated in osteolytic change and animal models have been developed there are few human tissue studies. There are no extensive human tissue studies comparing osteoarthritic hips to well fixed and loose prostheses. Methods. We have investigated 96 genes previously implicated in the osteolytic pathway. Genes were included based on previous implication in osteolysis in basic science studies. Candidates included cytokines, growth factors, apoptotic factors, matrix proteinases, interleukins, apoptotic proteins and macrophage activators. Results. One hundred patients were enrolled into the study and had intraoperative hip tissue removed after ethics approval. Patients were recruited from three cohorts, those undergoing primary hip replacement, revision of a well fixed prosthesis and revision for osteolytic change. A low density Taqman array method was used to determine gene expression for the 96 candidate genes. Expression of five housekeeping genes was measured and expression normalised between the samples. Statistical analysis was undertaken using significance testing and ROC analysis. There were seven candidate genes that were statistically significantly linked to aseptic loosening (p< 0.05) and strongly associated (AUC >0.77); these were BMP4, Frizzled related protein, fibroblast growth factor 18, IL8, IRAK 3, osteoprotegrin and PTGS2. There were a further nine genes which were highly predictive of osteolytic change (AUC >0.77), but did not reach significance (p>0.05): VEGFB, SFRP, TLR3, TLR5, TP53, IGF1, CTSK, CHIT 1 and CCL 18. Conclusion. We have been able to distinguish for the first time between factors which are associated with osteolytic change, those associated with exposure to wear debris in a well fixed prosthesis and those associated with the process of osteoarthritis

Purpose. Internal fixation of fractures in the presence of osteopenia has been associated with a failure rate as high as 25%. Enhancing bone formation and osseointegration of orthopaedic hardware is a priority when treating patients with impaired bone regenerative capacity. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications in implant integration. This study was designed to determine if FGF 18 promotes bone formation and osseointegration in the osteopenic FGFR3−/− mouse and to examine its effect on bone marrow derived mesenchymal stem cells (MSCs). Method. In Vivo: Intramedullary implants were fabricated from 0.4 × 10mm nylon rods coated with 300nm of titanium by physical vapour deposition. Skeletally mature, age matched female FGFR3−/− and wild type mice received bilateral intramedullary femoral implants. Left femurs received an intramedullary injection of 0.1μg of FGF 18 (Merck Serono), and right femurs received saline only. Six weeks later, femurs were harvested, radiographed, scanned by micro CT, and processed for undecalcified for histology. In Vitro: MSCs were harvested from femurs and tibiae of skeletally mature age matched FGFR3−/− and wild type mice. Cells were cultured in Alpha Modified Eagles Medium (αMEM) to monitor proliferation or αMEM supplemented with ascorbic acid and sodium beta-glycerophosphate to monitor differentiation. Proliferation was assessed through cell counts and metabolic activity at days 3, 6 and 9. Differentiation was assessed through staining for osteoblasts and mineral deposition at days 6, 9 and 12. Results. Wild type mice exhibited more peri-implant bone formation compared to FGFR3−/− mice. Peri-implant bone formation at the proximal metaphyseal-diaphyseal junction was increased in FGF18 treated femurs compared with contralateral control femurs in wild type (p = NS) and FGFR3−/− (p = 0.04) mice. Histological analysis corroborated micro CT findings, with FGF 18 treated FGFR3−/− femurs forming peri-implant bone instead of the fibrous response seen in controls. In vitro studies showed that FGF18 significantly increased MSC proliferation and metabolism in a dose dependent manner in wild type and FGFR3−/− mice. Osteoblast differentiation was inhibited by FGF18 in wild type MSCs, but was increased at physiological concentrations in cells harvested from FGFR3−/− mice. Conclusion. FGF 18 increases bone formation and osseointegration of intramedullary implants in osteopenic mice and increases MSC proliferation in both the presence and absence of FGFR3. FGF18 also promoted osteoblast differentiation in the absence of FGFR3 signalling, most likely via FGFR1 or 2. Additional work is needed to confirm the identity of the alternate FGFR and to evaluate its capacity to improve osseous healing in unfavourable in-vivo environments

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116