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Prevention of Maxillary Collapse During Sutural Distraction Osteogenesis for Cleft Palate Closure

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Prevention of Maxillary Collapse During Sutural Distraction Osteogenesis for Cleft Palate Closure Prevention of Maxillary Collapse During Sutural Distraction Osteogenesis for Cleft Palate Closure Miroslav S. Gilardino, BSc, MD Department of Experimental Surgery McGill University, Montreal, Quebec, Canada A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Master' s of Science (Experimental Surgery). July 2005 ~McGill'~-' © Miroslav Sergio Gilardino, 2005 Library and Bibliothèque et 1+1 Archives Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l'édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A ON4 Ottawa ON K1A ON4 Canada Canada Your file Votre référence ISBN: 978-0-494-22726-8 Our file Notre référence ISBN: 978-0-494-22726-8 NOTICE: AVIS: The author has granted a non­ L'auteur a accordé une licence non exclusive exclusive license allowing Library permettant à la Bibliothèque et Archives and Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l'Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans loan, distribute and sell theses le monde, à des fins commerciales ou autres, worldwide, for commercial or non­ sur support microforme, papier, électronique commercial purposes, in microform, et/ou autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in et des droits moraux qui protège cette thèse. this thesis. Neither the thesis Ni la thèse ni des extraits substantiels de nor substantial extracts from it celle-ci ne doivent être imprimés ou autrement may be printed or otherwise reproduits sans son autorisation. reproduced without the author's permission. ln compliance with the Canadian Conformément à la loi canadienne Privacy Act some supporting sur la protection de la vie privée, forms may have been removed quelques formulaires secondaires from this thesis. ont été enlevés de cette thèse. While these forms may be included Bien que ces formulaires in the document page cou nt, aient inclus dans la pagination, their removal does not represent il n'y aura aucun contenu manquant. any loss of content from the thesis. ••• Canada ABSTRACT Sutural distraction osteogenesis (SDO) has been proposed as a nove! approach for cleft palate closure in an effort to avoid the shortcomings oftraditional surgical repair. In this thesis, we present data that confirms that attempted distraction of the palatomaxillary suture (PMS) achieves cleft closure preferentially by alveolar arch collapse, and not by intended SDO. To that end, we have designed a novel custom-fit intraoral splint that successfully prevents maxillary collapse while facilitating cleft defect approximation via sutural distraction. Preservation of maxillary dimensions was confirmed via intraoral measurements and craniometrics. New bone deposition secondary to SDO was quantified with histomorphometry and microCT, while the effects of distraction on the PMS and palatal bone were assessed with histology and Dual­ energy Xray Absorptiometry (DXA). In summary, approximation ofpalatal defects via SDO in a canine model without maxillary collapse is possible, and may be a promising therapeutic approach for the repair of cleft palates in human infants. 1 RESUME L'ostéogenèse d'élongation de la suture a été proposée comme une approche originale de fermeture de la fente palatine afin de pallier aux insuffisances de la réparation chirurgicale traditionnelle. Dans cette thèse, nous présentons les données qui confirment qu'au moyen d'une élongation tentée de la suture maxillo-palatine, on réalise avec succès la fermeture de la fente aux dépens de l'effondrement maxillaire statistiquement important dans un modèle de palais fendu canin. Dans ce but, nous avons conçu une nouvelle attelle intra-buccale, réalisée sur mesure, qui évite avec succès l'effrondrement maxillaire tout en facilitant le rapprochement de la fente par l'élongation de la suture. L'effondrement maxillaire a été mesuré in vivo en intra-buccal et par craniométrie post mortem. L'ostéogenèse d'élongation de la suture a été corroboré par l'histomorpho-métrie et microCT. En résumé, la réparation des fentes palatines au moyen d'une élongation de la suture a des implications cliniques passionnantes pouvant être réalisée à la suite de la prévention de l'effondrement maxillaire, l'attelle intra-buccale décrite en complément. II ACKNOWLEDGMENTS AND CONTRIBUTION OF AUTHORS 1 would like to acknowledge my supervisor, Dr. H. Bruce Williams, for his continued guidance during this Master' s research project. 1 would also like to thank the McGill Plastic Surgery Research Fund for providing the financial assistance necessary to carry out this research. 1 would like to pay special thanks to Dr. Mark C. Martin, former Chief Resident, Plastic Surgery, McGill University, whose invaluable guidance and insight were paramount to the initiation and design of this project, and to its successful completion. My gracious thanks extend also to Mr. Hani Sinno, a medical student at McGill University whose commitment to this project and assistance with surgery and animal care is deeply appreciated. 1 am indebted to my collaborators, Dr. Janet Henderson and the technicians at the McGill Bone Centre, and Dr. Reggie Hamdy and his research assistant, Mrs. Dominique Lauzier. This collaboration, specifically under the guidance of Dr. Henderson, was essential to the histologie analysis of the data, an essential portion of this project. Specifically, 1 would also like to thank Mr. Jean-Sebastien Binette, Junior Engineer for his technieal expertise in acquiring and analyzing the micro CT imaging. 1 would like to individually thank Marie-Eve and Denise, the animal care technicians at the Montreal General Hospital Animal Surgieal Research Laboratory, whose dedication to animal care and well-being was exemplary. 1 am also indebted to Dr. M. Tanzer and Mr. Jan Krieger of the Orthopedie Research Lab, as weIl as the Faculty of Dentistry for the use of select surgieal instruments. 1 would also like to graciously thank Ms. Sara Solomon from the Faculty of Dentistry for her technical expertise and guidance necessary for the construction of the intraoral maxillary splints. For the data analysis portion of this research, 1 am indebted to Mr. Sebastien Dube, Clinieal Research Coordinator at the Montreal Children' s Hospital, whose statistieal expertise and data interpretation was not only contributory, but essential to the completion of this project. Finally, 1 would like to thank the McGill Surgieal Scientist Bursary program and the Plastic Surgery Educational Foundation (American Society of Plastic Surgery) via the 2004 Lyndon Peer Research fellowship for their generosity in providing the salary support for this project. The contribution of both parties is deeply appreciated. III TABLE OF CONTENTS ABSTRACT 1 RESUME II ~ - ~ " - ACKNOWLEDGMENTS AND CONTRIBUTION OF AUTHORS III TABLE OF CONTENTS IV TABLE OF FIGURES AND TABLES VI CHAPTERl: GENERAL INTRODUCTION 1 1.1 The Cleft Palate - Current Care and Future Prospectives 2 1.2 Sutural Distraction Osteogenesis for Cleft Palate Closure 2 1.3 Research Objectives 4 CHAPTER2: LITERATURE REVIEW 6 2.1 The Cleft Palate - Anatomical & Functional Derangement 7 2.2 Incidence and Etiology of Cleft Palates 9 2.3 Diagnosis and Standard of Care 10 2.4 Surgical Repair of the Cleft Palate 11 2.5 Timing of Cleft Palate Surgery 12 2.6 Pitfalls of CUITent Surgical Cleft Palate Repair 13 2.6.1 Morbidity and Mortality 13 2.6.2 Facial Growth Restriction 14 2.6.3 Orthodontie Complications 15 2.6.4 Unaddressed Bony Defect 16 2.6.5 Velopharyngeal Incompetence (VPI) 16 2.6.6 Surgical Revision of Secondary Deforrnities of Cleft Palate Repair 17 2.7 The Era of Tissue Engineering - Distraction Osteogenesis 17 2.7.1 The Biology of Distraction Osteogenesis 18 2.7.2 The Evolution of Distraction Osteogenesis - Application to the Craniofacial Skeleton 20 2.7.3 Sutural Distraction Osteogenesis - Distraction Without Osteotomy 20 2.7.4 Sutural Distraction Osteogenesis for Cleft Palate Closure - CUITent State of Knowledge 21 2.8 Alveolar Anchorage - Intraoral Maxillary Splint 24 N CHAPTER3: METROnS AND MATERIALS 26 3.1 Pilot Study 27 3.2 Surgical Induction of the Cleft Palate 27 3.3 Construction of the Custom-fit Acrylic Intraoral Maxillary Splint 29 3.4 Insertion of the Distractor Device +/- Intraoral Splint (Initiation of SDO) 31 3.5 Distraction Phase Data Collection - Intraoral Measurements 33 3.6 Experimental Endpoints 34 3.7 Histology 36 3.8 Histomorphometry 39 3.9 Micro-computed tomography (microCT) 40 3.10 Dual-energy Xray Absorptiometry (DXA) 42 3.11 Craniometry 42 CHAPTER4: RESULTS 45 4.1 Physical Examination 46 4.2 Gross intraoral morphology of the distraction process 47 4.2.1 Photographic documentation 47 4.2.2 Gross intraoral anatomical observations 50 4.3 Intraoral measurements 50 4.4 Craniometry 54 4.5 Histology 57 4.5.1 Low power microscopy 58 4.5.2 High power microscopy 60 4.6 Histomorphometry 65 4.6.1 Bone Percentage Composition Analysis 60 4.7 MicroCT 68 4.8 Dual-energy Xray Absorptiometry (Bone mineraI density) 71 CHAPTER5: DISCUSSION 72 CHAPTER6: SUMMARY OF RESULTS AND CONCLUSIONS 92 References 95 v LIST OF FIGURES AND TABLES Figure 2.1: Photographs of cleft lip and palate. 8 Fi2ure 2.2: Disoriented musculature in cleft palates. 9 Figure 2.3: Basic
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