SummaryThe free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchymederived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissuespecific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16 INK4a , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissuespecific anti-aging strategies.

ABSTRACT:It is generally supposed that the pattern of fracture healing in trabecular metaphyseal bone differs from that of diaphyseal fractures. However, few experimental studies to date have been performed, even though clinically many fractures occur in metaphyseal bone. Particularly, the influence of biomechanical factors has not yet been investigated under standardized conditions. Our aim was to correlate the interfragmentary strain (IFS) with the bone-healing outcome in a controlled metaphyseal fracture model in sheep. Twelve sheep received a partial osteotomy in the distal femoral condyle close to the trochlea. The determination of the IFS by in vivo X-ray analyses and a finite element model revealed that the deflection of the osteotomy gap by the patello-femoral force during walking provoked increasing strains of up to 40%. Bone healing was evaluated after 8 weeks by the assessment of the bone mineral density and by histomorphometry in regions of interest that displayed differing magnitudes of IFS. In areas with strains below 5% significantly less bone formation occurred compared to areas with higher strains (6-20%). For strains larger than 20% fibrocartilage layers were observed. Low IFS (<5%) led to intramembranous bone formation, whereas higher strains additionally provoked endochondral ossification or fibrocartilage formation. It is therefore proposed that metaphyseal bone healing follows similar biomechanical principles as diaphyseal healing.

Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff's base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.

Results: Compared with controls, 3 months of moderate or intermediate HHCY increased mean (SD) bone fragility at the femoral neck by 18% (6%) in methionine-fed (P ‫؍‬ 0.001) and 36% (13%) in homocystine-fed rats (P <0.001). Mean (SD) BAr/TAr at the distal femur in methionine and homocystine groups was decreased by 45% (21%; P ‫؍‬ 0.001) and 93% (9%; P ‫؍‬ 0.001), respectively. At the femoral neck, BAr/TAr was decreased by 19% (11%; P <0.001) and 55% (19%; P <0.001). At the lumbar spine, the reduction of BAr/TAr was 17% (23%; P ‫؍‬ 0.099) and 44% (19%; P <0.001). Plasma OC (bone formation marker) was decreased by 23% (20%; P ‫؍‬

The aim of the study was the development of a resorbable membrane for guided bone regeneration (GBR) with improved biocompatibility, which should be stiff enough to avoid membrane collapse during bone healing. Combining a bioactive ceramic with a resorbable polymer may improve the biocompatibility and osteoconductivity of resorbable devices. The present article describes the preparation, the mechanical properties, and the in vitro degradation characteristic of a composite membrane made of poly(L, DL-lactide) and alpha-tricalcium phosphate in comparison to a membrane made of pure poly(L, DL-lactide). The tensile strength and the elastic modulus as well as the molecular weight of the membranes were measured after in vitro degradation in buffer at 37 degrees C up to 28 weeks. The initial tensile strength of the composite and the polymer membrane was 37.3 +/- 2.4 MPa and 27.7 +/- 2.3 MPa and the elastic modulus 3106 +/- 108 MPa and 3101 +/- 104 MPa, respectively. The mechanical properties remained constant up to 8 weeks and then decreased slowly until week 28. The molecular weight of both membranes decreased steadily from 170,000 D to 30,000 D. It was concluded that the mechanical requirements for a membrane for GBR were fulfilled by the composite membrane.