Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells

The delicately orchestrated process of bone fracture healing is not always successful and long term non union of fractured bone occurs in 5-20% of all cases. Atrophic fracture non unions have been described as the most difficult to treat and this is thought to arise through a cellular and local failure of osteogenesis. However, little is known about the presence and osteogenic proficiency of cells in the local area of non union tissue. We have examined the growth and differentiation potential of cells isolated from human non union tissues compared with normal human bone marrow mesenchymal stromal cells (BMSC). We report the isolation and culture expansion of a population of non union stromal cells (NUSC) which have a CD profile similar to that of BMSC, i.e. CD34-ve, CD45-ve and CD105+ve. The NUSC demonstrated multipotentiality and differentiated to some extent along chondrogenic, adipogenic and osteogenic lineages. However, and importantly, the NUSC showed significantly reduced osteogenic differentiation and mineralization in vitro compared to BMSC. We also found increased levels of cell senescence in NUSC compared to BMSC based on culture growth kinetics and cell positivity for senescence associated beta galactosidase (SA-beta-Gal) activity. The reduced capacity of NUSC to form osteoblasts was associated with significantly elevated secretion of Dickkopf-1 (Dkk-1) which is an important inhibitor of Wnt signalling during osteogenesis, compared to BMSC. Conversely, treating BMSC with levels of rhDkk-1 that were equivalent to those levels secreted by NUSC inhibited the capacity of BMSC to undergo osteogenesis. Treating BMSC with NUSC conditioned medium also inhibited the capacity of the BMSC to undergo osteogenic differentiation when compared to their treatment with BMSC conditioned medium. Our results suggest that the development of fracture non union is linked with a localised reduced capacity of cells to undergo osteogenesis, which in turn is associated with increased cell senescence and Dkk-1 secretion.

Application of the finite element method to problems in fracture mechanics

Numerical techniques have been finding increasing use in all aspects of fracture mechanics, and often provide the only means for analyzing fracture problems. The work presented here, is concerned with the application of the finite element method to cracked structures. The present work was directed towards the establishment of a comprehensive two-dimensional finite element, linear elastic, fracture analysis package. Significant progress has been made to this end, and features which can now be studied include multi-crack tip mixed-mode problems, involving partial crack closure. The crack tip core element was refined and special local crack tip elements were employed to reduce the element density in the neighbourhood of the core region. The work builds upon experience gained by previous research workers and, as part of the general development, the program was modified to incorporate the eight-node isoparametric quadrilateral element. Also. a more flexible solving routine was developed, and provided a very compact method of solving large sets of simultaneous equations, stored in a segmented form. To complement the finite element analysis programs, an automatic mesh generation program has been developed, which enables complex problems. involving fine element detail, to be investigated with a minimum of input data. The scheme has proven to be versati Ie and reasonably easy to implement. Numerous examples are given to demonstrate the accuracy and flexibility of the finite element technique.

The relationship between fracture toughness and microstructure in titanium alloys

Linear Elastic Fracture Mechanics has been used to study the microstructural factors controlling the strength and toughness of two alpha-beta, titanium alloys. Fracture toughness was found to be independent of orientation for alloy Ti/6A1/4-V, but orientation dependent for IMI 700, bend and tension specimens giving similar toughness values. Increasing the solution temperature led to the usual inverse relationship between strength and toughness, with toughness becoming a minimum as the beta transus was approached. The production of a double heat treated microstructure led to a 100% increase in toughness in the high strength alloy and a 20% increase in alloy Ti/6A1/4V, with little decrease in strength. The double heat treated microstruoture was produced by cooling from the beta field into the alpha beta field, followed. by conventional solution treatment and ageing. Forging above the beta transus led to an increase in toughness over alpha beta forging in the high strength alloy, but had little effect on the toughness of Ti/6A1/4V. Light and electron microscopy showed that the increased toughness resulted from the alpha phase being changed from mainly continuous to a discontinuous platelet form in a transformed beta matrix. Void formation occurred at the alpha-beta interface and crack propagation was via the interface or across the platelet depending on which process required the least energy. Varying the solution treatment temperature produced a varying interplatelet spacing and platelet thickness. The finest interplatelet spacing was associated with the highest toughness, since a higher applied stress was required to give the necessary stress concentration to initiate void formation. The thickest alpha platelet size gave the highest toughness which could be interpreted in terms of Krafftt's "process zone size" and the critical crack tip displacement criterion by Hahn and Rosenfield from an analysis by Goodier and Field.

The fracture toughness of a range of cast steels

A range of plain carbon, carbon-manganese and low alloy cast steels were tested in order to determine their various fracture toughness values under elastic and elastic-plastic conditions. The main fracture toughness parameters which are considered are (1) Linear Elastic Fracture Mechanics (LEFM), (2) the J-Contour Integral, and (3) Crack Opening Displacement (COD). Results are obtained from fracture toughness specimens of various dimensions and the relevance of the validity criteria to cast steels is considered in some detail. In addition, the effect of casting position on specimen toughness values was noted. Valid KIC results according to LEFM, were obtained for three of the eight cast steels tested. Although KIC values from LEFM were not obtained from the remaining five steels, critical COD and J-integral values were determined. It is postulated that these values and particularly the critical J values can be used, with confidence for material selection or in defect tolerance calculations using these steels. Toughness values were found to vary with casting position in several of the steels tested and the possible reasons for such variations are discussed in the Thesis.

Ductile fracture mechanisms in a structural steel

Microstructural fracture processes in a BS4360 Grade 50D structural steel with lower sulphur content were studied in smooth tensile specimen tests and Charpy-size bend bar tests. Based on the experimental analysis, an experimental void growth relation with the plastic strain and stress triaxiality and multiplying factor on void growth were determined. Experimental results show that the void growth relation can be reasonably used to estimate the constraint in the specimens containing the notch or crack, also they can be used to evaluate the variations of the stress triaxiality in front of the notch and crack tip under general yielding condition. Side-grooves obviously increase the constraint of the CVN specimens. Strain hardening leads to increasing the stress triaxiality, and decelerating the net void growth. This is especially true for the values of stress triaxiality more than about one. Additionally, the effect of the stress triaxiality on the critical void growth corresponding to the onset of ductile tearing was preliminarily investigated. In this work, a large number of smaller specimens were tested to investigate the ductile-brittle transition behaviour of the structural steel. A void growth rate explanation was suggested for evaluating the temperature transition behaviour. The elastic-plastic fracture tough-ness values based on small specimen tests, such as pre-cracked side-grooved bending specimen and short bar tensile specimen, may give large overestimates of the plane strain fracture toughness.

Fracture toughness of a series of high chromium abrasion resistant alloys

The fracture properties of a series of alloys containing 15% chromium and 0.8 to 3.4% carbon are investigated using strain fracture toughness testing techniques. The object of the work is to apply a quantitative method of measuring toughness to abrasion resistant materials, which have previously been assessed on an empirical basis; and to examine the relationship between microstructure and K10 in an attempt to improve the toughness of inherently brittle materials. A review of the relevant literature includes discussion of the background to the alloy series under investigation, a survey of the development of fracture mechanics and the emergence of K10 as a toughness parameter. Metallurgical variables such as composition, heat treatment, grain size, and hot working are ???? to relate microstructure to toughness, and fractographic evidence is used to substantiate the findings. The results are applied to a model correlating ductile fracture with plastic strain instability, and the nucleation of voids. Strain induced martensite formation in austenitic structures is analysed in terms of the plastic energy dissipation mechanisms operating at the crack tip. Emphasis is placed on the lower carbon alloys in the series, and a composition put forward to optimise wear resistance and toughness. The properties of established competitive materials are compared to the proposed alloy on a toughness and cost basis.

The strength and fracture of engineering alloys at high temperature a collection of papers

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