Global ETD Search

1	The electromechanical properties of bone Mahmud, Fares A. January 1989 (has links) No description available. 571.4 Bone fracture healing
2	Bone healing measurement using acoustic resonances Nadav, O. January 1982 (has links) No description available. 610 Bone fracture healing
3	The mechanics of fracture healing Richardson, James Bruce January 1989 (has links) 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. 612 Bone fracture healing
4	Bone and ultrasound Mawhinney, Ian Nicholas January 1989 (has links) No description available. 610.28 Bone fracture healing
5	A study of mechanical influences on fracture healing, and on fracture non-union Watkins, P. E. January 1986 (has links) No description available. 610
6	Μοντελοποίηση πώρωσης οστών με τη μέθοδο των πεπερασμένων όγκων / Modeling of bone fracture healing with finite volume method Ποδαροπούλου, Αιμιλία 26 July 2013 (has links) Η διαδικασία πώρωσης καταγμάτων των οστών συμπεριλαμβάνει την ενεργοποίηση και αλληλεπίδραση διαφόρων κυττάρων, που ρυθμίζονται από βιοχημικά και μηχανικά σήματα. Στην παρούσα διπλωματική εργασία μελετάται το μαθηματικό μοντέλο πώρωσης καταγμάτων οστών, συμπεριλαμβανομένου μόνο των βιοχημικών ερεθισμάτων. Το μοντέλο αυτό, που αναπτύχθηκε αρχικά από τους Geris L. et al. (2008), περιλαμβάνει μία σειρά μερικών μη γραμμικών διαφορικών εξισώσεων που περιγράφουν την χωροχρονική εξέλιξη των συγκεντρώσεων και των πυκνοτήτων των κυτταρικών τύπων, των τύπων εξωκυττάριας θεμέλιας ουσίας και των αυξητικών παραγόντων που συμμετέχουν στη διαδικασία πώρωσης. Η προσομοίωση του μαθηματικού μοντέλου πώρωσης οστών έγινε μέσω υπολογιστικού κώδικα πεπερασμένων όγκων στο Matlab. Ιδιαίτερη έμφαση δίνεται στην διαδικασία της αγγειογένεσης που λαμβάνει χώρα κατά την πώρωση των καταγμάτων και αποτελεί σημαντικό παράγοντα για την αποκατάσταση των οστών και την πλήρη επαναφορά τους στην αρχική κατάσταση. Για την καλύτερη κατανόηση των διαδικασιών αγγειογένεσης, εκτός από την μελέτη του μαθηματικού μοντέλου της πώρωσης των οστών, πραγματοποιήθηκε μελέτη των βιολογικών διαδικασιών επούλωσης δερματικής πληγής και προσομοίωση με υπολογιστικό κώδικα στο Matlab του απλοποιημένου μαθηματικού μοντέλου της αγγειογένεσης στην επούλωση δερματικών πληγών. / The process of fracture healing involves the action and interaction of many cells, regulated by biochemical and mechanical signals. This postgraduate dissertation studies a mathematical bone fracture healing model for the case of normal fracture healing including only the biochemical factors (a bioregulatory model). The mathematical model, which was originally established by Geris L. et al. (2008), consists of a system of nonlinear partial differential equations describing the spatiotemporal evolution of concentrations and densities of the cell types, extracellular matrix types and growth factors indispensable to the healing process. The simulation of mathematical model was held by a computational finite volume code in Matlab. Particular emphasis is given to the process of angiogenesis, which occurs during fracture healing and is a key factor for bone repair and restore of the original state. For a better understanding of angiogenesis processes, a study in biological processes for dermal wound healing was held and a simulation of a simplified mathematical model of angiogenesis in healing dermal wounds by a computational code in Matlab. Κατάγματα 617.15 Bone fracture healing Fractures
7	TARGETED DELIVERY OF DASATINIB FOR ACCELERATED BONE FRACTURE REPAIR Mingding Wang (6624113) 25 June 2020 (has links) <p>Approximately 6.3 million bone fractures occur annually in the USA, resulting in considerable morbidity, deterioration in quality of life, loss of productivity and wages, and sometimes death (e.g. hip fractures). Although anabolic and antiresorptive agents have been introduced for treatment of osteoporosis, no systemically-administered drug has been developed to accelerate the fracture healing process. To address this need, we have undertaken to target a bone anabolic agent selectively to fracture surfaces in order to concentrate the drug’s healing power directly on the fracture site. We report here that conjugation of dasatinib to a bone fracture-homing oligopeptide via a releasable linker reduces fractured femur healing times in mice by ~60% without causing overt off-target toxicity or remodeling of nontraumatized bones. Thus, achievement of healthy bone density, normal bone volume, and healthy bone mechanical properties at the fracture site is realized after only 3-4 weeks in dasatinib-targeted mice, but requires ~8 weeks in PBS-treated controls. Moreover, optimizations have been implemented to the dosing regimen and releasing mechanisms of this targeted-dasatinib therapy, which has enabled us to cut the total doses by half, reduce the risk of premature release in circulation, and still improve upon the therapeutic efficacy. These efforts might reduce the burden associated with frequent doses on patients with broken bones and lower potential toxicity brought by drug degradation in the blood stream. In addition to dasatinib, a few other small molecules have also been targeted to fracture surfaces and identified as prospective therapeutic agents for the acceleration of fracture repair. In conclusion, in this dissertation, we have successfully targeted dasatinib to bone fracture surfaces, which can significantly accelerate the healing process at dasatinib concentrations that are known to be safe in oncological applications. A modular synthetic method has also been developed to allow for easy conversion of a bone-anabolic warhead into a fracture-targeted version for improved fracture repair.</p><p></p> Biochemistry Organic Chemistry Bone fracture healing Bone Biology Dasatinib
8	TP508 maintains chondrocyte cell viability through blocking apoptosis in an NO-dependent manner Zhong, Ming 27 November 2006 (has links) TP508 is a 23 amino acid peptide derived from human prothrombin. It helps wound healing in both soft tissues and bones. In our previous study, we have demonstrated that TP508 retains chondrocyte in a less mature differentiation state while expanding the cartilage mass, indicating it may partly help bone healing by expand the cartilage template in the endochondral bone formation stage. In our current study, we want to demonstrate that TP508 also blocks chondrocyte apoptosis. We used rat costochondral growth plate chondrocytes as our model. We first established chelerythrine as an apoptogen in chondrocytes. TP508 is able to block apoptosis caused by chelerythrine. Chelerythrine also causes an increase in NO production, which is known to cause both pathological and physiological apoptosis of chondrocyte, and blocking NO production can in turn block apoptosis caused by them. TP508 is also able to block NO production caused by chelerythrine. Therefore, TP508 may partially block chondrocyte apoptosis by blocking NO production. From all above, we conclude that besides decreasing chondrocyte differentiation, TP508 also blocks their apoptosis, so as to conserve the cartilage template in endochondral bone formation Bone fracture healing Chondrocyte NO Growth plate TP508 Amino acids Peptides Wound healing Cartilage cells Apoptosis Nitric oxide
9	Impact of the adaptive immune system in bone fracture healing Schlundt, Claudia 29 August 2017 (has links) 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. Knochenheilung Immunsystem Regulatorische T-Zelle Osteoimmunologie immune system osteoimmunology regulatory t cell bone fracture healing 570 Biowissenschaften; Biologie WF 9895 WW 5503 ddc:570
10	TARGETED DELIVERY OF BONE ANABOLICS TO BONE FRACTURES FOR ACCELERATED HEALING Jeffery J H Nielsen (8787002) 21 June 2022 (has links) <div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div> Genetics not elsewhere classified Nanobiotechnology Animal behaviour Clinical microbiology Endocrinology Nanomedicine Regenerative medicine (incl. stem cells) Solid state chemistry Molecular medicine Proteins and peptides Solution chemistry Radiation and matter Biomaterials Biomechanical engineering bone fracture healing Anabolic Agents/pharmacology Targeted Drug DeliveryDesign Bone fracture targeted drugs Bone theapeutics targeted therapies Growth factors Neuropepetides Extracellular matrix Extracellular matrix fragments spinal fusion Angiogensis Acidic oligopeptides osteoporosic fractures diabetic bone fractures Integrin alpha 5 Acelerated Bone fracture healing Hydroxyapatite Hydroxyapatite targeting Targeting peptides Peptide drugs osteomyelitis (OM) Rheumatoid arthritis Bone fractures osteogenic therapies osteotropic osteotropic nanomedicines osteoinductive capacity Molecular Medicine Organic Chemistry Proteins and Peptides Radiochemistry Solid State Chemistry Solution Chemistry Biochemistry Animal Behaviour Biological Engineering Biotechnology Genetics Medicine Pharmacology Biomaterials Biomechanical Engineering Biomechanics Endocrinology Nanobiotechnology Nanomedicine

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