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1
Sandberg, Olof. "Metaphyseal Fracture Healing." Doctoral thesis, Linköpings universitet, Avdelningen för kliniska vetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-126148.
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Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general. My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs. First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models. Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology. The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes. To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.
2
Hardy, John R. W. "Tibial diaphyseal fracture healing." Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/34096.
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Gill, Peter John. "Ultrasonic assessment of fracture healing." Thesis, Queen's University Belfast, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356863.
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Richardson, James Bruce. "The mechanics of fracture healing." Thesis, University of Aberdeen, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.290866.
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The mechanics applied to healing fractures vary widely. At one extreme rigid internal fixation is advocated, while at the other early mobilisation is recommended using external splints. Kuhn's method of paradigm orientated research was used to define the historical context of current assumptions regarding fracture healing. Conflict between the various schools of thought is the main evidence for failure of these assumptions and the need to evolve a new perspective on fracture healing. A paradigm is presented which proposes healing by external callus as an early stage and 'primary healing' as the later stage as of one continuous but changing process. A fundamental hypothesis was tested: that mechanics is the major control of fracture healing in man. A multicentre study of 102 patients with serious fractures were treated with external skeletal fixation. In 60 patients rigid external fixation was applied. In the remaining 42 the same fixation device was used, but adapted to apply 1 to 2mm of cyclic axial micromovement across the fracture. A piston applied 500 cycles of movement over a 30 minute period each day until this could be achieved by the patient on weight-bearing. Objective assessment required development of new techniques of measuring fracture stiffness and defining the point of healing. This objective measure, and clinically defined healing, were significantly faster in the group treated with micromovement (two-way analysis of variance, p = 0.005 and 0.03, respectively). Repeated injury by plastic deformation is proposed to maintain callus growth in the first phase of healing. Evidence for the required parameters of movement was gathered from the trial of micromovement, from measurements in 4 cases of epiphyseolysis and also 8 patients undergoing arthrodesis. It would appear appropriate to apply cyclic axial displacement of 2mm within the first two weeks from injury and of consistent direction until sufficient bulk of callus is formed. Thereafter axial compaction is appropriate in a second phase where callus matures. The mechanics that govern remodelling were considered to apply to the final phase. Failure of a cell culture model to display obvious results from cyclic loading may indicate that the response to mechanical loading is indirect. Intermediate and mechanically dependent biochemical and bioelectrical factors are discussed.
5
Wade, Roger. "Defining fracture union." Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249450.
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Shroff, Malav. "Effect of age on fracture healing." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393369.
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Gheduzzi, Sabina. "Fracture healing assessment by quantitative ultrasound measurements." Thesis, University of Bath, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341701.
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8
Dawson, Sarah P. "Digital X-ray analysis for monitoring fracture healing." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4285.
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X-ray based evaluation of different stages of fracture healing is a well established clinical standard. However, several studies have shown plain radiography alone to be an unreliable method to assess healing. The advent of digital X-ray systems provides the potential to perform quantitative analysis on X-ray images without disrupting normal clinical practice. Two aspects were explored in this study. The first was the measurement of mechanical fracture stiffness under four point bending and axial loading. The second was the inclusion of an Aluminium step wedge to provide Aluminium-equivalent thickness calibration information. Mechanical sti ness studies involved the development of equipment to perform four point bending on intra-medullary (IM) nailed tibial fractures, equipment to perform axial loading on conservatively treated humeral fractures, and fracture models to ex- amine the developed systems. Computational procedures to automatically measure the angle and offset occurring at the fracture site by comparing loaded and unloaded X-ray images were developed utilising cross-correlation. The apparatus and procedures were tested using the fracture models both in X-ray and using the Zwick materials testing machine. The four point bending system was applied clinically to a series of IM nailed tibial fracture patients and the axial loading system to two conservatively treated humeral fracture patients. Mechanical stiffness results showed that the apparatus worked well in the clinical radiography environment and was unobtrusive to normal practice. The developed X-ray analysis procedure provided reliable measurements. However, in the case of IM nailed tibial fractures, both angular and displacement movements were too small to be accurately assessed or to provide reliable stiffness measurements. This indicated that this patient group was possibly unsuitable for mechanical stiffness measurements or that higher loads needed to be applied to the fracture site. The case studies of conservatively treated humeral fractures showed potential in detecting movement between loaded and unloaded X-rays and using this to provide sti ness information. Further investigation is required to show that this technique has the potential to aid fracture healing monitoring. Investigation into Aluminium step wedge calibration began with the design of different step wedges and X-ray phantoms. Initial image analysis involved studying the automatic processing applied by a digital Computed Radiography (CR) Fuji sys- tem and modelling of the inhomogeneities in X-ray images as well as investigation into the effect of and correction for scatter, overlying soft tissue and bone thickness. Computational procedures were developed to semi-automatically detect the steps of the step wedge, form an exponential Aluminium step thickness to grey level calibration graph, measure soft tissue and bone thickness, and correct for the heel effect and scatter contributions. Tests were carried out on pre-clinical models and results compared to ash weight and peripheral quantitative computed tomography (pQCT). A clinical study of radial fractures was used to investigate the effectiveness of the step wedge calibration system in monitoring fracture healing changes. Results using the step wedge indicated that the calibration technique was e ective in detecting and correcting for aspects in uencing Aluminium-equivalent thickness measures. With careful processing, useful information was obtained from digital X- rays that included the Aluminium step wedge and these correlated well with existing density measures. The use of the wedge in patient images showed that small increases in Aluminium-equivalent thickness of the fracture site could be detected. This was most useful for intra-patient comparisons throughout the course of healing rather than providing quantitative measurements which were comparable to other density measures. In conclusion, this thesis shows the potential for accurate analysis of digital X- rays to aid the monitoring of healing changes in fracture patients, particularly with application of axial loading and the use of step wedge calibration.
9
Li, Jiang, and 李江. "Bone fracture healing in laminopathy-based premature aging." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45142233.
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Shirley, D. S. L. "Osteoblastic cells are systemically recruited during fracture healing." Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401767.
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Laycock, D. C. "Vibration analysis of fracture healing in long bones." Thesis, University of Salford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293031.
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Savaridas, Terence. "The effects of bisphosphonate on direct fracture healing." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/25158.
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Fractures repair by two distinct mechanism; indirect fracture healing via an endochondral stage and direct fracture healing with primary bone formation via osteonal remodelling units ('cutting cones'). Bisphosphonates are recommended by national clinical guidelines to reduce the risk of osteoporotic fractures. Despite bisphosphonate therapy, osteoporotic fractures continue to occur. A proportion of these fractures require rigid fixation, whereby bone repairs by direct fracture healing. The effects of bisphosphonate therapy on direct fracture healing have not been previously reported. With indirect fracture healing, therapeutic doses of bisphosphonate led to a delay in callus remodelling and a larger callus volume without detrimental effects on the physical property of healing fractures. A model of direct fracture healing with rigid tibial plating in the rat was developed. In addition, a non-rigid model of external fixation that used the same number and size of screw holes to that of the plating model was used for comparison. Implants were designed and tested in cadavers prior to preliminary studies in rats. Within these two groups, animals were randomly allocated either to receive daily injections of bisphosphonate (Ibandronate) or saline (Control) for nine weeks. Following three weeks of injections a transverse tibial osteotomy was created and stabilised. Plain radiographs were obtained at fortnightly intervals. Animals were sacrificed at six weeks post fracture stabilisation. On sacrifice, fracture healing was assessed on contact radiographs, with a 4-point bend to failure and histologically. The mechanical properties of the uninjured diaphyseal bone in the contra-lateral limb were also assessed following bisphosphonate therapy. The mean bending stress at failure of diaphyseal bone in the uninjured limb was increased by 20% following only nine weeks of bisphosphonate treatment. The increase in strength of the uninjured diaphyseal bone has relevance when normalising the strength of fracture repair in a limb when comparing it to the unfractured limb as frequently reported in animal studies of fracture repair. In direct fracture healing bisphosphonate therapy resulted in impaired fracture healing as evident on plain radiographs based on the visibility of the fracture line. At six weeks post fracture the failure stress on application of a 4-point bend was decreased and histology revealed delayed bone healing compared to controls. Ibandronate treatment had an inhibitory effect on direct fracture healing in a rodent model. In clinical practice, the treating surgeon may need to consider using non-rigid fixation methods in patients already on bisphosphonate therapy. When rigid fixation is essential patients on bisphosphonates will need to be monitored for features of delayed or non-union and the use of fracture healing adjuncts should be considered.
13
Yew, Alvin Garwai. "The equilibrium geometry theory for bone fracture healing." College Park, Md. : University of Maryland, 2008. http://hdl.handle.net/1903/8308.
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Thesis (M.S.) -- University of Maryland, College Park, 2008.Thesis research directed by: Dept. of Mechanical Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
14
Watkins, P. E. "A study of mechanical influences on fracture healing, and on fracture non-union." Thesis, University of Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376622.
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Reed, Anita A. C. "The biological activity of fracture non-unions." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249459.
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Vijayakumar, Vinod. "Stress/strain environments in healing human tibial fractures." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275202.
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Christersson, Albert. "Fractures of the distal radius : Factors related to radiographic evaluation, conservative treatment and fracture healing." Doctoral thesis, Uppsala universitet, Ortopedi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312931.
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Distal radius fractures (DRFs) are one of the most common injuries encountered in orthopaedic practise. Such fractures are most often treated conservatively, but surgical treatment has become increasingly common. This trend is not entirely scientifically based The aims of this thesis were threefold: to increase measurement precision in dorsal angulation (DA) on radiographs and computer tomographies (CTs); to assess the results after shortened plaster cast fixation time in reduced DRFs; and to evaluate the feasibility and safety of applying Augment® (rhPDGF-BB/β-TCP) in DRFs. In Paper I and Appendix 1 and 2, a semi-automatic CT-based three-dimensional method was developed to measure change in DA over time in DRFs. This approach proved to be a better (more sensitive) method than radiography in determining changes in DA in fractures of the distal radius. In Paper II, a CT model was used to simulate lateral radiographic views of different radial directions in relation to the X-ray. Using an alternative reference point on the distal radius, precision and accuracy in measuring DA was increased. Paper III and IV are based on a prospective and randomised clinical study (the GitRa trial) that compares clinical and radiographic outcomes after plaster cast removal at 10 days versus 1 month in 109 reduced DRFs. Three patients in the early mobilised group were excluded because of fracture dislocation (n=2) or a feeling of fracture instability (n=1). For the remaining patients in the early mobilised group (51/54) a limited but temporary gain in range of motion, but a slight increase in radiographic displacement were observed. Our results suggest that plaster cast removal at 10 days after reduction of DRFs is not feasible. Paper V is based on a prospective, randomised clinical study (the GEM trial) in which 40 externally fixated DRFs were randomised to rhPDGF-BB/β-TCP into the fracture gap or to the control group. Augment® proved to be convenient and safe during follow-up (24 weeks). However, because of the nature of the study design, the effect on fracture healing could not be determined. A decrease in pin infections was seen in the Augment® group, a finding we could not explain.
18
Varga-Vass, Anna. "Large-scale dynamic hydrofracturing, healing and fracture network characterization." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6846/.
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Permeability of a rock is a dynamic property that varies spatially and temporally. Fractures provide the most efficient channels for fluid flow and thus directly contribute to the permeability of the system. Fractures usually form as a result of a combination of tectonic stresses, gravity (i.e. lithostatic pressure) and fluid pressures. High pressure gradients alone can cause fracturing, the process which is termed as hydrofracturing that can determine caprock (seal) stability or reservoir integrity. Fluids also transport mass and heat, and are responsible for the formation of veins by precipitating minerals within open fractures. Veining (healing) thus directly influences the rock’s permeability. Upon deformation these closed factures (veins) can refracture and the cycle starts again. This fracturing-healing-refacturing cycle is a fundamental part in studying the deformation dynamics and permeability evolution of rock systems. This is generally accompanied by fracture network characterization focusing on network topology that determines network connectivity. Fracture characterization allows to acquire quantitative and qualitative data on fractures and forms an important part of reservoir modeling. This thesis highlights the importance of fracture-healing and veins’ mechanical properties on the deformation dynamics. It shows that permeability varies spatially and temporally, and that healed systems (veined rocks) should not be treated as fractured systems (rocks without veins). Field observations also demonstrate the influence of contrasting mechanical properties, in addition to the complexities of vein microstructures that can form in low-porosity and permeability layered sequences. The thesis also presents graph theory as a characterization method to obtain statistical measures on evolving network connectivity. It also proposes what measures a good reservoir should have to exhibit potentially large permeability and robustness against healing. The results presented in the thesis can have applications for hydrocarbon and geothermal reservoir exploration, mining industry, underground waste disposal, CO2 injection or groundwater modeling.
19
Hanratty, B. M. "The Effect of TP508 on High Energy Fracture Healing." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501272.
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Manitzky, Louise J. "Mathematical modelling of intramembranous bone formation during fracture healing." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/78983/1/Louise_Manitzky_Thesis.pdf.
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During fracture healing, many complex and cryptic interactions occur between cells and bio-chemical molecules to bring about repair of damaged bone. In this thesis two mathematical models were developed, concerning the cellular differentiation of osteoblasts (bone forming cells) and the mineralisation of new bone tissue, allowing new insights into these processes. These models were mathematically analysed and simulated numerically, yielding results consistent with experimental data and highlighting the underlying pattern formation structure in these aspects of fracture healing.
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Lee, Geoffrey. "Targeting alarmins to accelerate healing." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:2ea58ae6-9d79-461a-a1d9-dff95c79794e.
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Promoting tissue repair in adults represents a major unmet medical need. Tissue regeneration relies on the activation of quiescent endogenous stem cells and whilst considerable progress has been made, novel therapies based on stem cells have thus far failed to translate to routine clinical practice. Much attention has focussed on administrating exogenous stem cells expanded or altered in vitro. However, this approach faces several major limitations, including poor engraftment, high cost and importantly, the necessity for immunosuppression for allogenic cells. An alternative strategy that overcomes these shortcomings is to promote repair by harnessing the regenerative potential of endogenous stem cells. This thesis focussed on the role of alarmins, the upstream group of mediators released immediately following injury, in promoting tissue regeneration. I show that the alarmin HMGB1 accelerates tissue regeneration in various systems by transitioning multiple stem cell types from the quiescent G0 to the GAlert state. Firstly, in vitro screening of candidate alarmins with human bone marrow-derived mesenchymal stromal cells showed that only pre-treatment with HMGB1 improved osteogenic differentiation. Using an optimised murine fracture model, I found that local administration of HMGB1 accelerated bone regeneration via the CXCL12-CXCR4 axis, whilst healing was impaired in inducible Hmgb1-/- animals. Cell cycle analyses revealed that HMGB1 transitioned the skeletal stem cell from G0 to GAlert. In this intermediate phase, the cell is more metabolically active and efficiently enters the cell cycle when exposed to activating factors. This effect also extended to other types of stem cells, including murine haematopoietic and muscle stem cells, as well as human haematopoietic stem and progenitor cells, and MSCs. Using murine models, HMGB1 accelerated recovery from injury to these tissues. Finally, treatment with a single systemic dose of HMGB1 two weeks before injury also accelerated bone, haematopoietic, and muscle regeneration, which was indicative of an acquired pro-regenerative signature. These findings document that the HMGB1-GAlert pathway results in a dynamic and adaptive multi-tissue regenerative response, and suggest that exogenous HMGB1 may be of therapeutic benefit in diverse clinical contexts, including trauma, chemotherapy, and elective surgery.
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Fallon, Jessica Anne. "Crack healing as a function of pOH- and fracture morphology." Texas A&M University, 2004. http://hdl.handle.net/1969.1/1369.
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Crack healing in quartz has been investigated by optical microscopy and interferometry
of rhombohedral ( 1 1 10 ) cracks in polished Brazilian quartz prisms that were annealed
hydrothermally at temperatures of 250°C and 400°C for 2.4 to 240 hours, fluid pressure
Pf = Pc = 41 MPa, and varying pOH- (from 5.4 to 1.2 at 250°C for fluids consisting of
distilled water and NaOH solutions with molalities up to 1). Crack morphologies before
and after annealing were recorded for each sample in plane light digital images. Crack
apertures were determined from interference fringes recorded using transmitted
monochromatic light (l = 598 nm). As documented in previous studies, crack healing is
driven by reductions in surface energy and healing rates are governed by diffusional
transport; sharply defined crack tips become blunted and split into fluid- filled tubes and
inclusions. A rich variety of fluid inclusion geometries are also observed with nonequilibrium
shapes that depend on initial surface roughness.
Crack healing is significant at T=400°C. Crack healing is also observed at T=250°C for
smooth cracks with apertures <0.6 mm or cracks subject to low pOH-. The extent of
crack healing is sensitive to crack aperture and to hackles formed by fine-scale crack
branching during earlier crack growth. Crack apertures appear to be controlled by
hackles and debris, which prop the crack surfaces open. Upon annealing, crack
apertures are reduced, and these reduced crack apertures govern the kinetics of
diffusional crack healing that follows. Hackles are sites of either enhanced or reduced
loss of fluid-solid interface, depending on slight mismatches and sense of twist on
opposing crack surfaces. Hackles are replaced either by healed curvilinear quartz
bridges and river patterns surrounded by open fluid-filled crack, or by fluid- filled tubes
surrounded by regions of healed quartz. For a given temperature, aperture and anneal
time, crack healing is enhanced at low pOH- ( £ 1.2) either because of changes in the
hydroxylated quartz- fluid interface that enhance reaction rates or because of increased
rates of diffusional net transport of silica at high silica concentrations.
23
Murray, Alastair W. "Fracture healing in osteopenic bone and the influence of simvastatin." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/29286.
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In part one of the study 20, 3-month-old female, Wistar rats underwent ovariectomy (Ovx) while a further 20 had a sham procedure to act as controls. Seven weeks later a transverse fracture was created in the proximal tibia of each animal by three-point bending with the resulting fractures supported by an intramedullary wire. Half of the animals in each group were euthanased at two weeks and the remainder at four weeks post fracture with tibiae removed post mortem. All tibiae were then x-rayed. The mechanical properties of half of the healing fractures were ascertained by four-point bending to failure while the remaining specimens were prepared for histological analysis and immunohistochemistry. There were no mechanical differences in the fracture calluses from the ovx animals compared with control at two weeks but by four weeks post fracture the ultimate load at failure of the fractures from the ovx animals were rescued to 71% of that from controls. Stiffness (54%) and stress at yield (74%) were also reduced while the strain at yield was increased by 40% in fractures from the ovx group. In the second part of the study the same animal model was used with the groups once again divided into ovx and sham controls. Half of each group received placebo while the other half received simvastatin 20mg/kg daily for 14 days post fatigue. The same time points and outcome measures were used as in the first part of the study. The dose and method of delivery of simvastatin had no apparent effect on the fracture healing in normal bone. However simvastatin appeared to have a deleterious effect on fracture healing in the osteopenic model causing a reduction in callus size and maturity and reducing the healing fractures’ ability to withstand load. This study does not support a role for simvastatin in the enhancement of fracture healing in osteopenia.
24
Niemeyer, Frank [Verfasser]. "Simulation of fracture healing : applied to distraction osteogenesis / Frank Niemeyer." Ulm : Universität Ulm. Medizinische Fakultät, 2013. http://d-nb.info/1043262245/34.
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Nakagawa, Yasuaki. "Calcium-Dependent Neutral Proteinase(Calpain)in Fracture Healing of Rats." Kyoto University, 1994. http://hdl.handle.net/2433/168857.
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本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものであるKyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第5555号
医博第1525号
新制||医||577(附属図書館)
UT51-94-C13
京都大学大学院医学研究科外科系専攻
(主査)教授 畑中 正一, 教授 岡 正典, 教授 山室 隆夫
学位規則第4条第1項該当
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Kaluarachchi, Thambilipitiyage Kusumsiri Priyantha Kumara. "Impact of collagen type X deficiency on bone fracture healing." Thesis, Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23501807.
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Nyquist, Fredrik. "The influence of alcohol on bone metabolism and fracture healing." Lund : Lund University, Dept. of Orthopaedics, Malmö University Hospital, 1998. http://catalog.hathitrust.org/api/volumes/oclc/39792795.html.
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Eveleigh, Rebecca. "A biomechanical evaluation of intramedullary nails during simulated fracture healing." Thesis, University of Bath, 1997. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362194.
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Schütte, Andrea. "Autoantibodies against growth factors and their receptors in fracture healing." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17656.
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Die Knochenregeneration während der Frakturheilung beinhaltet das Zusammenspiel von Wachstumsfaktoren. In einigen Patienten kommt es zu einer verzögerten oder unvollständigen Heilung. Die Gründe hierfür sind bisher nicht komplett verstanden. Neutralisierende Autoantikörper (aAB) gegen Wachstumsfaktoren oder deren Rezeptoren könnten den Heilungsprozess verzögern und potentiell beeinträchtigen In dieser Arbeit wurden 265 Frakturpatienten analysiert. Autoantikörper gegen IGF1 Rezeptor, Insulin Rezeptor, BMP7, BMP2, IGF1 und (Pro)Insulin wurden in den Seren dieser Frakturpatienten gemessen. In Frakturpatienten wurden in 5% der Seren aAB gegen den IGF1R und in 6% gegen den IR gefunden. Das Auftreten von IGF1R- und IR-aAB wurde nicht induziert und war nicht mit dem Heilungsergebnis assoziiert. BMP7-aAB wurden in 1-2,5% gesunder Probanden und Frakturpatienten, die nicht mit rhBMP7 behandelt wurden, detektiert. Patienten, die mit rhBMP7 behandelt wurden, zeigten ein höheres Auftreten der BMP7-aAB Positivität mit 6% zum Zeitpunkt der Operation und 18% vier Wochen nach der Operation. BMP2-aAB wurden in 2% der gesunden Kontrollen und 6% der mit rhBMP7-behandelten Frakturpatienten entdeckt. Bei der Charakterisierung des biologischen Effekts der BMP7-aAB durch einen zell-basierten Reporter-Assay, zeigte sich ein neutralisierender Effekt in Proben mit hohem BMP7-aAB Titer. Als das wichtigste Kriterium für klinische Relevanz wurde die Konsolidierung untersucht. Das Vorhandensein von BMP-aAB wurde nicht signifikant mit der Konsolidierung in Zusammenhang gebracht. Zusammenfassend wurden neue diagnostische Assays zur Detektion von aAB gegen Wachstumsfaktoren und deren Rezeptoren generiert und angewandt um aAB in Seren von Frakturpatienten zu messen. Keiner der identifizierten aAB war negativ mit dem Heilungsprozess assoziiert. Bedenken bezüglich der Sicherheit von rhBMP7 Behandlungen sind berechtigt, da die Anwendung aAB gegen BMP7 induziert, die den BMP7-Signalweg blockieren.Regeneration of bone during fracture healing includes concerted actions of growth factors. Some fractures show delayed healing or non-union due to as yet unknown reasons. Neutralizing autoantibodies (aAB) against growth factors or their receptors might influence and potentially impair the bone healing capacity. In this study, a cohort of 265 fracture patients with different treatment regimen and healing outcomes were analysed. Autoantibodies against IGF1 receptor, insulin receptor, BMP7, BMP2, IGF1 and (pro)insulin were measured in sera of these fracture patients. The prevalence of aAB against IGF1R and IR was 5% and 6% in fracture patients, respectively. The appearance of IGF1R- and IR-aAB was not induced by the surgical intervention and was unrelated to the healing outcome. BMP7-aAB were found in 1-2.5% of healthy subjects and in fracture patients that were not treated with rhBMP7. Patients that had received rhBMP7 treatment showed a higher incidence of BMP7-aAB positivity of 6% at surgery and 18% four weeks post surgery. BMP2-aAB were found in 2% of healthy controls and 6% of the fracture patients that were treated with rhBMP7. Characterizing the biological effect of BMP7-aAB in a cell-based reporter assay, a neutralizing effect was observed for samples with high titres. As the most relevant clinical outcome, the criterion consolidation was analysed defining whether the fracture gap was closed after six months or not. The presence of BMP-aAB was not significantly associated with the healing outcome. In summary, novel diagnostic assays for the detection and quantification of growth factor and receptor aAB were generated and used to determine aAB in sera from fracture patients. None of the identified aAB were negatively associated with the regeneration process or healing outcome. Ongoing concerns regarding the safety of rhBMP7 treatment are justified as the biological treatment induces aAB against BMP7 that block the BMP signal transduction.
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Schlundt, Claudia. "Impact of the adaptive immune system in bone fracture healing." Doctoral thesis, Humboldt-Universität zu Berlin, 2017. http://dx.doi.org/10.18452/18195.
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Knochengewebe besitzt die einzigartige Fähigkeit sich nach einem Bruch komplett zu regenerieren. Dennoch zeigen 10-15% der Patienten einen gestörten Heilungsverlauf. Das Immunsystem spielt eine entscheidende Rolle in der Frakturheilung. Im Rahmen der hier präsentierten Doktorarbeit wurde der Einfluss der CD4+ regulatorischen T-Zellen (Treg) auf die Knochenheilung untersucht. In einem Maus-Osteotomie-Modell wurde die zeitliche und räumliche Verteilung ausgewählter Immun- und Knochenzellen im osteotomierten Knochen untersucht. Dabei konnte gezeigt werden, dass Immunzellen im gesamten Heilungsverlauf in der Frakturzone zu finden waren und oft eine direkte Kolokalisation mit den Knochenzellen aufwiesen. Diese Ergebnisse zeigen deutlich die starke Interaktion beider Systeme. Ein adaptiver Transfer muriner Treg vor Setzen der Osteotomie diente als immunmodulatorischer Ansatz zur Verbesserung des Frakturheilungsprozesses. Tiere mit einem unerfahrenen Immunsystem (SPF-Haltung) zeigten eine verbesserte Heilung nach Treg-Transfer. Mäuse mit einem erfahrenen Immunsystem (semi-sterile Haltung) zeigten einen kontroversen Heilungserfolg: eine Hälfte der Mäuse heilte signifikant besser und die andere Hälfte signifikant schlechter. Die Schlechtheiler zeigten eine höhere Ratio von CD8+ Effektoren zu Treg im Vergleich zu den Gutheilern. In einer darauffolgenden Proof-of-concept-Studie konnte gezeigt werden, dass eine prä-OP definierte Ratio von CD8+ Effektoren zu Treg mit dem Heilungserfolg nach Osteotomie korrelierte.
Im Rahmen dieser Doktorarbeit konnte ein potentiell positiver Einfluss von CD4+ Treg auf den Frakturheilungsprozess bestätigt werden. Dennoch wurde auch der enorme Einfluss des prä-OP Immunstatus auf den Heilungserfolg deutlich. Für die Klinik ist es also im Rahmen einer Immuntherapie umso wichtiger Patienten-basierte Therapieformen zu entwickeln, bei denen der individuelle Immunstatus eines jeden Patienten vor Anwendung der Therapie berücksichtigt wird.Bone tissue possesses the remarkable capacity to fully regenerate after injury. However, in 10-15% of patients, unsuccessful bone repair is still a present problem. Components of the adaptive immune system play an indispensable role in bone regeneration. The here presented PhD thesis focused on the interaction of CD4+ regulatory T cells (Treg) during fracture healing. In a murine osteotomy model, the spatiotemporal distribution of immune and bone cells was analyzed within the healing bone. Cells of the immune system were detectable throughout the whole healing cascade in the injured area und showed often a direct co-localization with bone cells. These results highlight the interconnectivity of immune and bone cells during regeneration. By adoptive transfer of murine CD4+ Treg prior to osteotomy, an immunomodulatory approach to improve bone healing was conducted. Mice possessing an unexperienced immune system (SPF housing) showed a consistent improved healing outcome after adoptive Treg transfer. However, mice with a more experienced immune system (semi-sterile housing) receiving an adoptive Treg transfer demonstrated a controversial healing outcome: half of the mice showed a significantly improved and the other half a significantly poorer healing outcome. In the mice with a poorer healing outcome, a higher ratio of CD8+ effector T cells and Treg was observed. In a following proof of concept study, a pre-osteotomy defined ratio of CD8+ effector T cells and Treg could predict the healing outcome after adoptive Treg transfer and osteotomy. A potential positive impact of Treg in bone repair was confirmed in this study. However, the tremendous impact of the environment and thereby of the immune status prior to immunomo-dulation was also clearly demonstrated. Hence, for the clinic, it is even more important to develop and to apply patient based immunomodulatory treatment approaches considering the individual immune status of each patient prior to treatment.
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Chehade, Mellick Joseph. "Bone resonance analysis, histomorphometry and the mechanics of fracture healing." Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phc515.pdf.
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Aird, J. "Human Immunodeficiency Virus and open fractures : is wound or fracture healing affected in surgically stabilised open fractures? : a prospective study." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1343913/.
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Background: 33 million people worldwide are infected with HIV, a complex disease that affects many of the processes involved in wound and fracture healing. There is little evidence available to guide acute management of open fractures in these patients and fears of acute and delayed sepsis often inhibit the use of surgical fixation, which may be the most effective way of achieving union. This study addresses the hypothesis that the presence of either HIV or advanced HIV (CD4 count <=350) leads to an increased risk of complications in patients with open fractures treated with surgical stabilization. South Africa has one of the highest rates of both HIV and high energy trauma in the world, so was deemed an appropriate place for the study of this interaction. Methods: This prospective observational study compared surgical fixation of open fractures in HIV positive and negative patients. 133 patients with 135 open fractures fulfilled the inclusion criteria. 86 fractures were in HIV negative and 33 in HIV positive patients. The remaining 16 patients refused HIV tests. 12 HIV positive patients had advanced disease (CD4 <=350), 14 had early disease (CD4 >350), 7 refused CD4 count testing. This cohort was three times larger (number of HIV positive patients) than any similar previously published study. There was no randomised allocation; the treatment of these patients was based on locally developed protocols and was dependent on; fracture type, location and the grade of wound. Patients were followed up either till union had been achieved or for 6 months in tibia/femur fractures, and 3 months in other fractures. The primary outcome was acute wound infection, secondary outcomes tested were fracture union and pin site sepsis. The analysis of the binary nominal data was done using the Chi squared test. In cases where the expected value was less than 5, then the Fisher’s exact test was used. In the assessment of multiple potential risk factors, binary logistic regression was used. Results: Analysis of background characteristics showed that HIV positive and negative populations were broadly similar with regard to demographics, injury type/location and grade of wound. In the analysis of the primary outcome, the risk of wound infection was marginally higher in patients without HIV (22%) as compared to patients with HIV (15%). This difference was small and did not reach statistical significance (n=135, Risk Ratio 0.7, p value 0.40). However, as hypothesized, the infection risk was higher in patients with advanced HIV (26%), compared to patients with early HIV (5%). The numbers, however, were small and this did not reach statistical significance (n=33, Risk Ratio=4.8, P value= 0.12). Sub group analyses, conceived prior to the study, provided strong evidence that patients with Gustilo Anderson grade 1 injuries had a higher risk of wound infection in patients with advanced HIV than controls (HIV negative and early HIV) (n=46, Risk Ratio=6.3, P value =0.02). Of note, departmental guidelines meant that patients with grade 1 injury were not prioritised for theatre and had, on average, a delay of 3.5 days to surgery. The average delay was similar in both HIV positive and negative groups. Analysis of the secondary outcome, nonunion, provided strong evidence that the risk of nonunion was higher in HIV positive than HIV negative patients (n=115, Risk Ratio=4.1, P value=0.04). Interestingly, the patients with advanced HIV had a slightly lower nonunion risk (13%) than patients with early HIV (20%). However the numbers were small and the difference was not statistically significant (n=33, Risk Ratio=0.8, P value=1). The incidence of nonunion was not correlated with the presence of wound infection. The risk of mild pin site sepsis in fractures treated with external fixation was similar in both HIV positive (60%) and negative (67%) patients (n=31, Risk Ratio=0.9, P value=1). An increased risk of severe pin site sepsis was noted in patients with advanced HIV (50%), compared to controls (25%). Although the difference is large, the numbers are small and the difference was not statistically significant (n=28, Risk Ratio=2, P value= 0.31). It would require 160 patients to prove a difference of this size. Conclusions: Data from this study appears to dispute the conclusion of previous studies that suggest that all patients with HIV are at higher risk of wound infection, and therefore internal fixation should be considered with caution. In this study it was only the patients with advanced HIV that showed a small increase in the risk of wound infection. Based on this study the author suggests that early HIV should not be a contraindication to either internal or external fixation in open fractures, due to concerns of wound infection. However, advanced HIV should continue to be considered a relative contraindication to internal fixation, until further data becomes available. Since this finding applied equally to grade 1 (Gustilo Anderson) injuries, the data suggests that any theatre delays in patients with advanced HIV may be detrimental to outcomes. This is contrary to published data that suggests that grade 1 injuries do not need to be prioritised. The data provides strong evidence that HIV leads to an increased risk of non unions. Interestingly, the risk of non union is less in patients with advanced HIV. This may fit with recently published laboratory studies suggesting that the absence of lymphocytes is beneficial to bone healing. Based on this evidence the author suggests that in patients with HIV treatment strategies should be aimed at achieving union, rather than on potentially unfounded concerns of preventing infection. In patients treated with external fixation, the data provides weak evidence of an increased risk of severe pin site sepsis in advanced HIV. This observation may be due to an increased susceptibility to infection, or to problems with bone healing in these patients. Based on this evidence, and the evidence that patients with HIV may be at increased risk of non union, the author suggests that HIV positive patients being treated with external fixators, should be considered for treatment strategies that will prolong the life of the pin bone interface. These may include additional pins, wires and/or the use of hydroxyapatite coated half pins.
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Li, Jian. "Spontaneous correction of fracture deformity : a study in the rat /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-119-9/.
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Oess, Ninja P. "Strain measurements using magnetoelastic sensing for wireless bone fracture healing assessment /." Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17550.
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Pietsch, Martin [Verfasser]. "Modelling the fracture healing process with interface capturing techniques / Martin Pietsch." Ulm : Universität Ulm, 2019. http://d-nb.info/1175527068/34.
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Pfeiffenberger, Moritz [Verfasser]. "Mimicking the initial phase of fracture healing in vitro / Moritz Pfeiffenberger." Berlin : Freie Universität Berlin, 2021. http://d-nb.info/123689748X/34.
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Mahmud, Fares A. "The electromechanical properties of bone." Thesis, Staffordshire University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254325.
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Mawhinney, Ian Nicholas. "Bone and ultrasound." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335942.
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Fourie, Jeanette Ann. "Stimulation of bone healing in new fractures of the tibial shaft using interferential currents." Master's thesis, University of Cape Town, 1994. http://hdl.handle.net/11427/27041.
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The aims . of this research were twofold, firstly to find out if interferential currents could reduce the healing time for fractures of the tibia and thereby prevent nonunion and secondly to develop a model which could predict nonunion, given the subject characteristics such as race, mechanism of injury, severity of fracture etc. Subjects, males only between the ages of 12 and 86, who had sustained fractures of the tibiae were entered into this double blind clinical trial on admission to the orthopaedic wards at Groote Schuur Hospital (between January 1989 and October 1991). According to strict inclusion and exclusion criteria, a final sample of 227 cases (208 subjects) were entered by block randomisation into three groups; an experimental group (n=41), placebo group (n=35) and control group (n= 151). lnterferential currents were applied to the experimental group via suction electrodes for, 30 minutes per day for 10 days, using a beat frequency of 10 - 25 Hz and a swing mode of 6 ϟ 6. The placebo group had the suction electrodes applied which produce a rhythmical massage effect. Subjects commented on pain relief which resulted in the addition of the control group as a check on the possible effect of suction, the control group received no intervention. The data were analysed firstly, by using the ANOV A with continuous covariates which resulted in a finding of no significant difference in the time taken to union for the three groups. The second statistical analysis using the same data set, were logistic regression models demonstrating risk factors for nonunion within 24, 32 and 40 weeks. These models were then validated, showing sensitivity and specificity for a variety of possible cutoffs. The conclusions reached about the validity of these models were that they could not be used to predict, accurately enough, those cases where surgical intervention would be necessary; however, for low cost non-invasive intervention they may have value.
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Nemchand, Jaya Luxshmi. "Smart implant : the biomechanical testing of instrumented intramedullary nails during simulated callus healing using telemetry for fracture healing monitoring." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/11592.
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The purpose of this study is to investigate the effect of loading during long bone fracture healing in-vitro and in-vivo. Fracture healing has until now only been monitored using radiographs and ultrasound. An intramedullary nail instrumented with strain gauges has the potential to monitor loading in-vivo during bone fracture healing. Strain has been previously monitored over time though external fixation devices however there has been no published data about monitoring through a nail. The load carried by a telemetric intramedullary nail during simulated fracture healing is monitored in-vitro with the aid of custom designed jigs, integrated in a biomechanical test frame. Clinically predetermined loading conditions are applied to the construct and synthetic bone composites are used developed to simulate mechanical strength of early to mature osteogenic bone, approximating natural healing processes. Four different synthetic bone composites have been designed and developed to mimic the mechanical properties of granulation tissue, fibrous tissue, cartilaginous tissue and immature bone. Three different generations (GEN I – IIIa) of intramedullary nails were developed and biomechanically tested in-vitro. GEN I and II were purely biomechanical nails that underwent compression, torsional and 4pt bend tests. Different fracture patterns and callus morphology were simulated and tested biomechanically. Circumferential and segmental application of the synthetic materials were applied on the artificial fractured bone instrumented with GEN I. Observations from live animal study provided x-rays from which callus growth patterns were extracted and repeated in-vitro. Cadaveric biomechanical tests and pre-clinical trial of GEN IIIa was conducted. The aim was to repeat the biomechanical tests while at the same time monitoring healing with an instrumented nail implanted in an induced fractured, ovine left hind limb. A loading rig was designed for the in-vivo test. The hypothesis proposed is that forces experienced by an intramedullary nail will progressively decrease as fracture heals. Results from GEN I have shown that strain measurement can be monitored during fracture healing in-vitro. The GEN IIIa nail is yet to be tested in-vivo for the same biomechanical tests for comparison. There is currently no published study on simulating fracture healing with accuracy.
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Löffler, Julia [Verfasser]. "Impact of the local metabolic milieu on bone fracture healing / Julia Löffler." Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1192304195/34.
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Weber, Agnes Johanna [Verfasser]. "Fracture healing and glucocorticoids in HSD2 transgenic mouse model / Agnes Johanna Weber." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2012. http://d-nb.info/1026694914/34.
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Bunn, Robert Jonathan. "Pro-inflammatory cytokines in delayed fracture healing induced by local muscle crush." Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397898.
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Mounts, Alexander Kim. "Effects of a BMP antagonist on fracture healing in a mouse model." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12165.
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Thesis (M.A.)--Boston UniversityIntroduction: Fracture healing is a complex process that is responsible for forming a fracture callus to stabilize the site of injury while producing new bone. Delayed fracture healing or the development of non-union as a result of failed fracture healing is a major clinical concern effecting ~10% of all treated fractures. Recent studies have shown that RAP-661, an antagonist of Bone Morphogenetic Proteins (BMP) 2 and BMP-4 binding to its receptor BMPR-1A has shown anabolic efficacy in treating bone loss associated with osteoporosis. The purpose of this study was to assess the effectiveness of the RAP-661 protein as a therapeutic agent to improve fracture healing. Materials and Methods: 34 C57/B6 mice received unilateral mid-shaft transverse right femur fractures. Three study groups used: Vehicle Treated Control (10 mM Tris-Buffered Saline) and RAP-661 in 10 mM TBS either where the drug treatment was administered continuously over the 35 days of the study or administered with a delayed treatment beginning 14 day after fracture. Both drug and vehicle were administered via intraperitoneal injection twice per week. RAP-661 was administered at 10 mg/kg for each injection. The mice were terminally harvested at 35 days. The harvested femora were then tested via microCT analysis for material and structural properties and by mechanical testing for strength and torsional stiffness and rigidity. Results: MicroCT testing showed that both drug groups had increased bone volume and bone volume percentage. Mechanical testing however, showed that the control group was significantly stronger based on its maximal torque to failure than both either drug treatment group. Although not significant, the 35 day delay group showed comparable stiffness and rigidity to the control and trended toward higher values compared to the 35 day continuous group. Conclusion: Although both drugs groups had increased total mineral density and percentage bone volume, they both had significantly lower maximal torque to failure when compared to the control. This discordance indicates that while the RAP-661 improves overall bone accumulation, it is effecting the structural integrity of bone bridging in some manner that compromise the regain of the bone’s normal mechanical strength. Further research will be needed to resolve the mechanism(s) behind this phenomenon. These results indicate that RAP- 661 does not show therapeutic efficacy in promoting fracture healing.
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Spencer, Robert F. "The effect of head injury on fracture healing : clinical and experimental studies." Thesis, University of Edinburgh, 1990. http://hdl.handle.net/1842/19310.
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Scarpa, Edoardo. "Polymeric nanoparticles loaded with a Wnt agonist for enhancing bone fracture healing." Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/408720/.
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In the UK, over 2 million people suffer a bone fracture every year. 10% of bone fractures will not heal adequately and require surgical intervention and, as yet, there is no approved systemic drug that is effective in promoting and accelerating fracture healing. Wnt signalling activation is a promising therapeutic target to address this paucity of treatments. Wnt is a molecular pathway that controls bone homeostasis and repair. However, its activation can have both positive and negative effects on bone cell function depending on the timing and site of delivery. Polymersomes (PMs) are polymeric nanoparticles that allow for a spatio-temporal controlled delivery of molecules, including Wnt agonists. This study addresses the hypothesis that PMs loaded with a Wnt agonist can be used as a novel systemic treatment to accelerate bone fracture healing fracture. The aims were: to assess cellular uptake of PMs and to quantify the amount of payload released intracellularly from PMs, to determine the ability of Wnt agonist loaded PMs to promote the osteogenic differentiation of human bone marrow stromal cells (BMSCs), and to assess the distribution of PMs in vivo following systemic injection in a mouse model of bone fracture. Cellular uptake was demonstrated using fluorescein as a model payload. By combining microscopy and flow cytometry, it was demonstrated that PMs are internalised by different cell types, including skeletal stem cells (SSCs), and real-time intracellular release of fluorescein was quantified at a single-cell level. Activation of Wnt signalling was achieved loading PMs with the Wnt agonist 6-bromoindirubin-3’-oxime (BIO), and demonstrated using a luciferase assay and RT-qPCR. In a reporter cell line, BIO-PMs induced a significant activation of the Wnt pathway without cytotoxicity, differently from free BIO. In BMSCs, BIO PMs induced a significant increase in the expression of the Wnt target gene AXIN2 (p < 0.05) and in the expression of the early osteogenic marker RUNX2 (p < 0.05). Biodistribution in vivo was assessed loading PMs with a fluorescent dye (DiR) and using IVIS and histological analysis. PMs localised in the fractured bone within 24 hours after systemic administration in mice with a femoral drill defect and reached the maximum of accumulation after 48 hours. Histological sectioning confirmed the presence of PMs in the defect area post injection. Preliminary results demonstrated that BIO-PMs injected systemically have the ability to promote bone formation after injury. This project demonstrated that PMs are internalised by SSCs, which are the ideal cellular targets for bone regenerative approaches. When loaded with Wnt agonists, PMs induce a controlled activation of the pathway, promoting osteogenic differentiation of BMSCs. Upon systemic injection in vivo, PMs accumulate at the fracture site and were able to promote bone formation. Overall, the novel and exciting findings presented in this project showed that PMs loaded with Wnt agonists could represent an effective pharmacological treatment to promote bone regeneration after fracture.
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Shen, Kaitlin. "The Role of Activated Protein C in Bone, Arthritis, and Fracture Healing." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14376.
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Activated protein C (APC) is a cytoprotective anticoagulant that stimulates cellular proliferation, suppresses inflammation, and enhances wound healing. These properties of APC are primarily modulated through its receptors, endothelial protein C receptor (EPCR) and protease-activated receptors (PAR)1/2, and subsequent activation of downstream proteins including ERK1/2, Akt, and p38. In this study, APC was investigated for its potential application in bone repair and arthritic bone conditions, including rheumatoid arthritis (RA) and osteoarthritis (OA), through its actions on osteoblasts. APC increased viability of MG-63 and MC3T3-E1 cells through a PAR1 dependent pathway and subsequently upregulated pERK, pAkt, and p-p38. APC augmented bone and tissue volume but not osteoclast numbers in a BMP-2 induced murine ectopic bone formation model. APC, however, did not enhance callus formation in a closed murine mid-tibial fracture model owing to several study limitations. In contrast with its effects in osteoblastic cell lines, APC suppressed cell viability through an EPCR/PAR1/PAR2 dependent mechanism in OA and RA bone derived cells. APC also decreased pERK, increased p27, and modulated IL-6 and MMP-2 secretion in arthritic cells. Collectively, these results demonstrate the diverse actions of APC in normal and arthritic bone biology including the novel potential of APC on bone formation.
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Salem, Khaled Hamed [Verfasser]. "Analysis of delayed fracture healing following unreamed tibial nailing / Khaled Hamed Salem." Ulm : Universität Ulm. Medizinische Fakultät, 2004. http://d-nb.info/1015471188/34.
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Brugo, Tommaso Maria <1985>. "Fracture Toughening and Self-Healing of Composite Laminates by Nanofibrous Mats Interleaving." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amsdottorato.unibo.it/7950/1/Tommaso%20Maria%20Brugo%20PhD%20Thesis.pdf.
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Composite laminates present important advantages compared to conventional monolithic materials, mainly because for equal stiffness and strength they have a weight up to four times lower. However, due to their ply-by-ply nature, they are susceptible to delamination, whose propagation can bring the structure to a rapid catastrophic failure. In this thesis, in order to increase the service life of composite materials, two different approaches were explored: increase the intrinsic resistance of the material or confer to them the capability of self-repair.
The delamination has been hindered through interleaving the composite laminates with polymeric nanofibers, which completed the hierarchical reinforcement scale of the composite. The manufacturing process for the integration of the nanofibrous mat in the laminate was optimized, resulting in an enhancement of mode I fracture toughness up to 250%.
The effect of the geometrical dimensions of the nano-reinforcement on the architecture of the micro one (UD and woven laminates) was studied on mode I and II. Moreover, different polymeric materials were employed as nanofibrous reinforcement (Nylon 66 and polyvinylidene fluoride). The nano toughening mechanism was studied by micrograph analysis of the crack path and SEM analysis of the fracture surface.
The fatigue behavior to the onset of the delamination and the crack growth rate for woven laminates interleaved with Nylon 66 nanofibers was investigated. Furthermore, the impact behavior of GLARE aluminum-glass epoxy laminates, toughened with Nylon 66 nanofibers was investigated.
Finally, the possibility of confer to the composite material the capability of self-repair was explored. An extrinsic self-healing-system, based on core-shell nanofibers filled with a two-component epoxy system, was developed by co-electrospinning technique. The healing potential of the nano vascular system has been proved by microscope electron observation of the healing agent release as result of the vessels rupture and the crosslinking reaction was verified by thermal analysis.
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Watson, Hilary Joy. "Longitudinal study of recovery following diaphyseal fracture of the tibia or femur." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/19399.
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