University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-4-2019 The Effect of Emdogain Periodontal Regenerative Material on Inflammation in eriodontalP Maintenance Patients Jessica M. Gradoville University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Periodontics and Periodontology Commons Recommended Citation Gradoville, Jessica M., "The Effect of Emdogain Periodontal Regenerative Material on Inflammation in Periodontal Maintenance Patients" (2019). Theses & Dissertations. 367. https://digitalcommons.unmc.edu/etd/367 This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. THE EFFECT OF EMDOGAIN PERIODONTAL REGENERATIVE MATERIAL ON INFLAMMATION IN PERIODONTAL MAINTENANCE PATIENTS By Jessica Marie Gradoville, D.D.S. A THESIS Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of Requirements for the Degree of Master of Science Medical Sciences Interdepartmental Area (Oral Biology) Under the Supervision of Professor Amy C. Killeen University of Nebraska Medical Center Omaha, Nebraska May 2019 Advisory Committee: Richard A. Reinhardt, D.D.S., Ph.D. Jeffrey B. Payne, D.D.S., M. Dent. Sc. James K. Wahl III, Ph.D. Sung K. Kim, D.D.S. i ACKNOWLEDGMENTS Research has played an integral role in my education and career for many years, so when beginning my periodontal residency the decision to continue being involved in research was a simple one. My journey in research began while pursuing my undergraduate degree and progressed through dental school; however, I was never conducting the research I was investigating. That all changed thanks to the support I received from my periodontal faculty. From the very start, I was excited about the end goal because I knew this was a strong project and one that pertains well to the field of periodontics. I cannot thank enough all of those who have provided unlimited guidance along my journey. Dr. Killeen sets a perfect example of what it takes to be a researcher, mentor, instructor, and role model, and my heartfelt thanks goes out to her. Dr. Killeen supported me in every aspect of my life, from clinical work, to research, to personal life. She was not only there for the big moments, but the small moments as well. Whenever I had a question or was unsure of the next step, she was available and willing to help. She never wavered in her support. Without her guidance, this thesis would not have been possible. I thank her for her valuable advice and inspiration during my residency. My research committee was an integral part of my success and I would like to extend my gratitude to each member. Dr. Richard Reinhardt, who helped keep me on track and provided extensive knowledge and advice throughout my residency. Dr. Jeffrey Payne for his insightful suggestions and unparalleled knowledge, your contributions were invaluable. Dr. James Wahl and Dr. Sung Kim, thank you for offering constructive criticism and assistance throughout the study. I cannot begin to express my thanks to my co-resident and friend, Dr. Erica Jasa. Dr. Jasa supported and challenged me each day of residency. Her clinical skills and assistance played a pivotal role in this research project. Without her encouragement, advice, and companionship, I would not be the person I am today. ii Especially helpful to me during this time were Mrs. Megan Christiansen, Mrs. Marian Schmid, and Kaeli Samson. Without Mrs. Megan Christiansen, this research project could not have been completed. Thank you for playing the largest role in treating patients and providing the greatest care. Mrs. Marian Schmid was instrumental in the lab, working tirelessly and providing loyal support when evaluating the lab samples. Kaeli Samson helped us with the statistical analysis and ultimately interpreted our data. To the patients who took part in this yearlong study, they also deserve recognition. Without your participation and interest, we would not have been able to accomplish this project. Funding for this study was provided by Windsweep Farm (Lincoln, NE), the late Dr. Mick Dragoo and his wife, Mary, as well as the Nebraska Society of Periodontology and the University of Nebraska Medical Center College of Dentistry Surgical Specialties Department. Your contributions and aid in this project are appreciated. Special thanks goes to my husband, CJ, my son, Theodore, and my parents, Kirk and Rachele. CJ has stood by my side, through the good and the bad, the last twelve years. He understands my passion and love for knowledge and I would not be the person I am without his support. Theodore was born in the thick of my thesis development and writing, I hope one day I make him proud. My parents have given my constant love and encouragement throughout my education. I thank them for believing in me, from the very beginning. I love you all. THE EFFECT OF EMDOGAIN PERIODONTAL REGENERATIVE MATERIAL ON INFLAMMATION IN PERIODONTAL MAINTENANCE PATIENTS Jessica M. Gradoville, D.D.S., M.S. University of Nebraska, 2019 Advisor: Amy C. Killeen, D.D.S., M.S. The purpose of this double-blinded, randomized, controlled clinical trial was to determine if local application of enamel matrix protein derivative (Emdogain:EMD), combined with minimally-invasive papilla reflection is effective in reducing inflammation in periodontal pockets in patients on periodontal maintenance therapy (PMT). Fifty patients diagnosed with advanced chronic periodontitis presenting with a 6-9mm interproximal probing depth were included in the trial. Experimental (EMD; n=24) and control (saline, n=26) therapies were randomly allocated. Roots were treated with mini-flaps and root planing assisted with endoscope evaluation before EMD or saline application. Inflammation was assessed by bleeding on probing (BOP) at baseline, 6-, and 12-months and gingival crevicular fluid (GCF) samples at baseline, 2-weeks, 6-, and 12- months. GCF was evaluated for change in IL-1β and PGE2 levels using ELISA. A significant reduction in BOP at the treatment site was seen for both groups after 12-months. After adjustments, patients with BOP present at baseline had a higher risk of a poor BOP outcome at 12-months (AOR = 5.68, p = 0.048). At 2-weeks, there was a significant reduction in IL-1β with EMD (mean = -40.15 pg, p = 0.05) and at 12-months a trend for reduction in IL-1β with EMD (mean = -32.85 pg, p = 0.07). Differences in IL-1β between groups were not significant. The addition of EMD does not significantly improve BOP; however, EMD does significantly decrease IL-1β in the short-term compared to a control in periodontal maintenance patients. iv TABLE OF CONTENTS ACKNOWLEDGEMENTS...............................................................................................................i ABSTRACT....................................................................................................................................iii TABLE OF CONTENTS.................................................................................................................iv LIST OF FIGURES.........................................................................................................................vi LIST OF TABLES..........................................................................................................................vii LIST OF ABBREVIATIONS…………………………………………………………………...viii CHAPTER 1: INTRODUCTION.....................................................................................................1 CHAPTER 2: LITERATURE REVIEW: PERIODONTITIS..........................................................3 CHAPTER 3: LITERATURE REVIEW: ENAMEL MATRIX DERIVATIVE.............................6 CHAPTER 4: LITERATURE REVIEW: MICROSURGERY AND PERIOSCOPE...................10 CHAPTER 5: LITERATURE REVIEW: INTERLEUKIN-1β AND PROSTAGLANDIN E2.....13 CHAPTER 6: RESEARCH HYPOTHESIS AND SPECIFIC AIMS………………....................17 CHAPTER 7: MATERIALS AND METHODS……....................................................................18 Patient population and study design…………………………………………………………...18 Data collection and treatment protocol………………………………………………………..21 Analysis of GCF samples………………………………………………………………………...24 Statistical analyses………………………………………………………………………………..25 CHAPTER 8: RESULTS…............................................................................................................28 Patient characteristics……………………………………………………………………………28 Clinical outcomes…………………………………………………………………………………29 Inflammatory biomarker outcomes………………………………………………………….….34 CHAPTER 9: DISCUSSION……………………………………………………………………..40 v CHAPTER 10: CONCLUSION……………………………………………………………….…48 BIBLIOGRAPHY...........................................................................................................................49 APPENDIX A: RAW CLINICAL DATA- PATIENT CHARACTERISTICS.............................59 APPENDIX B: RAW CLINICAL DATA- BOP…………………………………………………61 APPENDIX C: RAW CLINICAL DATA- Il-1β..………………………………………………..63 APPENDIX D: RAW CLINICAL DATA- PGE2…………………………………………….…..65 APPENDIX E: CONSENT FORM………………………………………………………………67 vi LIST OF FIGURES Figure 1: Study Design Flowchart ................................................................................................ 20 Figure 2: Baseline