published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

A research report submitted to the School of Oral Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Dentistry in the branch Maxillofacial and Oral Surgery. Johannesburg 2014 / The reconstruction of osseous mandibular defects remains a significant challenge. The use of autologous bone for mandibular reconstruction is associated with numerous limitations, and alternatives to autologous bone would provide significant benefits for patients. The aim of this study was to evaluate and compare binary application of recombinant human bone morphogenetic protein 7 (rhBMP-7) and recombinant human transforming growth factor  (rhTGF-3) to solo application of recombinant human bone morphogenetic protein 7 (rhBMP-7) in full-thickness mandibular defects in the non-human primate Papio ursinus. In four baboons, a 2.5cm segmental defect was created in the mandible and stabilized with a 2.7mm titanium reconstruction plate. Two defects were implanted with rhBMP-7 solo, and the other two with binary application rhBMP-7 and rhTGF-3 at a ratio of 20:1. All four baboons were euthanazed at 180 days post implantation. All four specimens were radiographed prior to sectioning. Tissue processing and histomorphometry were done on the undecalcified sections prepared from the harvested mandible specimens. In all defects bone regeneration re-established bony continuity at six months. The mean area of the regenerate was 336 ± 107.5 mm2 (range 229-444.7) in the solo specimens, and 312 ± 63.5mm2 (range 249-376.6) in the binary specimens. Radiographic examination confirmed complete bone healing in all defects but variable restitution of defect volume. The regenerated bone had a trabecular pattern consistent with mature mandibular bone and the defect interfaces were indiscernible. Due to the small sample size no performance advantage could be identified between the two treatment groups. These results confirm that successful bone regeneration by tissue induction in surgically created mandibular defects can be achieved with osteogenic proteins of the transforming growth factor- superfamily.

Made available in DSpace on 2014-06-11T19:31:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-05Bitstream added on 2014-06-13T18:41:38Z : No. of bitstreams: 1 colli_vc_dr_araca.pdf: 1176842 bytes, checksum: 7b5e4f64a86568d1041b8b5218994711 (MD5) / A ação da ocitocina (OT) como regulador direto da massa óssea foi reportada em roedores jovens e este efeito anabólico foi atribuído à ação periférica deste hormônio. O objetivo deste estudo foi investigar a ação periférica de OT no processo de reparo alveolar de ratas Wistar de 12, 18 e 24 meses. Ratas de 12 meses com ciclo estral normal e ratas de 18 e 24 meses em diestro permanente receberam duas injeções intra-peritoniais (12 horas de intervalo) de salina (NaCl 0,15M – grupos controle) ou OT (134g/Kg – grupos tratados). Sete dias após, o incisivo direito foi extraído e as análises foram realizadas com 28 dias de reparo alveolar (35 dias após administração de salina ou OT). Os resultados plasmáticos de cálcio e fósforo não diferiram entre os grupos. Os marcadores bioquímicos sistêmicos de formação óssea, fosfatase alcalina (FAL) e osteocalcina (OC), não revelaram diferença significativa de valores na comparação entre grupos controle e tratado de 12 meses, porém esta diferença foi significativa para os dois marcadores quando os animais tratados de 18 e 24 meses foram comparados com os respectivos controles. A análise histomorfométrica e a reação de imunohistoquímica contra OC confirmaram estes resultados mostrando que o tratamento com OT, promoveu maior formação óssea nos animais de 18 e 24 meses. O marcador sistêmico de reabsorção óssea, fosfatase ácida resistente ao tartarato (TRAP) não foi estatisticamente diferente entre animais dos grupos controle e tratado de 12 e 18 meses, porém nos de 24 meses este valor foi significativamente menor nos animais tratados indicando diminuição de reabsorção por ação de OT nos animais desta idade. A imunomarcação para TRAP realizada nos cortes alveolares confirmou os... / The action of oxytocin (OT) as a direct regulator of bone mass has been reported in young rodents and this anabolic effect was attributed to the peripheral action of this hormone. The aim of this study was to investigate the peripheral action of OT in the process of alveolar repair of Wistar rats with 12, 18 and 24 months. Rats of 12 months with normal estrous cycle and rats with 18 and 24 months in permanent diestrus received two intra-peritoneal injections (12 hours apart) of saline (NaCl 0.15 M - control group) or OT (134  g / kg - treated groups). Seven days later, the right incisor was extracted and the analyzes were performed with 28 days of alveolar repair (35 days after administration of saline or OT). The plasma results of calcium and phosphorus did not differ between groups. The systemic biochemical bone formation markers, alkaline phosphatase (ALP) and osteocalcin (OC), revealed no significant difference of values in animals of 12 months, but this difference was significant for both markers when treated animals of 18 and 24 months were compared to controls. The histomorphometric analysis and immunohistochemical reaction against osteocalcin confirmed these results showing that treatment with OT, promoted greater bone formation in animals with 18 and 24 months. The systemic marker of bone resorption, tartrate-resistant acid phosphatase (TRAP) was not statistically different between animals of the control and treated groups of 12 and 18 months, but in 24 months the values were significantly lower in treated animals indicating decreased resorption action of OT in animals of this age. The immunostaining for TRAP performed on alveolar cuts confirmed the results of the results of systemic markers in groups of 12 and 24 months... (Complete abstract click electronic access below)

Thesis (D.Eng.)--Cleveland State University, 2009. / Abstract. Title from PDF t.p. (viewed on Jan. 13, 2010). Includes bibliographical references (p. 139-151). Available online via the OhioLINK ETD Center and also available in print.

published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

Background Distraction osteogenesis (DO) was first applied on the human craniofacial skeleton in 1992 by McCarthy et al.1 who performed lengthening of the mandible in patients with hemifacial microsomia and Nager’s syndrome. Further advances in this field have since then led to the widespread use of this modality for the treatment of numerous congenital and acquired craniofacial skeletal anomalies. In 2001, a review by Swennen et al2 concluded that up to year 1999, this form of treatment was gaining intense popularity but that the main drawbacks included insufficient data on long term results and relapse. A systematic review of the last decade on functional outcomes and long term complications following distraction osteogenesis of the facial skeleton is presented. Methods A structured systematic literature search, with predefined inclusion and exclusion criteria from relevant computer databases and journals were performed. The journals were evaluated and critically appraised by 2 reviewers separately in 3 rounds. Papers were categorized according to the level of evidence, the quality of methodology and the specific field of functional outcomes and long term complications. Results were then categorized according to the type of distraction movements, ie maxillary advancement and mandibular lengthening. Results A total of 42 papers comprising of 16 studies for maxillary advancement and 26 studies for mandibular lengthening were included in this review. Maxillary advancement was found to be beneficial in patients with cleft maxillary hypoplasia in terms of achieving aesthetic outcome but the risk for velopharyngeal insufficiency remains uncertain. The achieved maxillary advancement was stable if performed on adult patients while a recurrence of midface retrusion was noted if DO was performed on growing patients. Overcorrection was recommended in these cases to an estimated value of 20-50%. Mandibular lengthening was 99% successful in relieving respiratory obstruction in patients with isolated Pierre Robin Sequence (PRS) or syndromic micrognathic infants preventing the need for tracheostomy in the long term, and in 89% successfully decannulating infants with pre-existing tracheostomy. However, feeding and growth outcomes after airway obstruction was relieved remain unknown due to lack of sufficient evidence. Unilateral mandibular DO was successful in achieving aesthetic symmetrical facial balance in patients with hemifacial microsomia however a total loss of corrected distraction length was noted by the end of growth period if DO was performed during growth. Conclusions DO achieved stable results in terms of lengthening the maxilla and mandible but was also noted to cause restricted growth potential of the distracted bone. Hence, the benefits of performing DO during active growth should be weighed against the likely need for a second surgery due to a growth deficit of distracted bone and future surrounding bone growth. However DO in adults remains an alternative to conventional orthognathic surgery and choice of treatment should be patient centred. / published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

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No description available.

Despite advances in bone grafting technology for musculoskeletal injury, re-injury or incomplete healing persists. Efforts to modify bone allografts sing proteins and growth factors show improvement in wound healing outcomes. We use FTY720, an agonist of S1P receptors 1 and 3, to improve bone graft integration through bone regeneration and vascularization. Four methods of delivering FTY720 into a bone defect are described: 1) FTY720 loaded onto a PLAGA-coated bone allograft and implanted in a critical size rat cranial defect; 2) FTY720 loaded onto a PLAGA-coated bone allograft and implanted in a rat tibial defect; 3) FTY720 loaded into a Matrigel plug and injected into a mouse tibial fracture; and 4) FTY720 directly adsorbed to human bone xenografts and implanted in a critical size rat cranial defect. In each of these models, FTY720 release was characterized, and bone regeneration and vascularization was monitored within the defect. Additionally, local tissue composition and immune response was evaluated. The results presented here indicate that FTY720 released locally into the bone defect improved new bone formation and vascularization, promoting improved graft integration.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.