Blood Perfusion and Early Wound Healing Following Implant Placement
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Blood Perfusion and Early Wound Healing Following Implant Placement: A Comparison Between Grafted and Non-Grafted Sites Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Vrisiis Kofina, DDS Graduate Program in Dentistry The Ohio State University 2018 Thesis Committee: Dr. Binnaz Leblebicioglu, Advisor Dr. Dimitris Tatakis Dr. Barbaros Selnur Erdal Copyright by Vrisiis Kofina, DDS 2018 Abstract Objective: This study aimed to determine the rate of recovery from surgical trauma through blood perfusion following implant placement surgery and to develop a reliable method to determine volumetric and linear changes within buccal bone following implant placement surgeries using Cone Beam Computed Tomography (CBCT). CBCT-related results were compared with previously used technique to evaluate regenerated bone volume within similar anatomical location. Materials and methods: Patients receiving single non-molar implant in the maxillary esthetic zone were recruited. Data collection was performed at the day of surgery; 3, 6, 9 days; 1 and 4 months, postoperatively. Soft tissue healing was recorded using well-established wound healing parameters during the entire healing period. Wound fluid collected at 3, 6 and 9 days and gingival crevicular fluid (GCF) collected at baseline, 1 and 4 months from the adjacent teeth was used for future multiplex analysis of metabolism mediators. Soft tissue biopsies were collected from the wound site at baseline, 9 days and 4 months and stored for future bone remodeling related gene expression analysis. Buccal flap blood perfusion using Laser Doppler Flowmetry (LDF) was recorded immediately before and after implant placement surgery, at 3, 6, 9 days and, 1 and 4 months. Soft tissue biotype and ii implant stability quotient (ISQ) were determined at the time of implant placement and at 4 months. Bone thickness changes along the peri-implant buccal wall were evaluated by automatic superimposition of two CBCTs taken immediately after surgery and at 4 months. Peri-implant buccal bone changes along the length of the implant were calculated by using a software. Buccal bone grey values were selected based on soft tissue and bone grey values after automatic superimposition of images. Patients receiving extraction and bone regeneration [socket preservation (SP) or guided bone regeneration (GBR)] within similar anatomical location were recruited. Two CBCTs were taken with a timeline as described above. Buccolingual, linear and volumetric measurements targeting buccal bone thickness were performed manually by using standard marks embedded into surgical guides or by using adjacent teeth to define the area of interest while comparing two CBCTs obtained from the same subject. The advantages and disadvantages of both techniques were discussed. Descriptive statistics are reported as mean±se and percentage. Patient was chosen as unit of measurement. A linear mixed model regression analysis was used for repeated continuous measures fixed and random effects within and between groups. A random effect (intercept and slope) regression analysis was conducted to estimate the slopes of the outcome over continuous time for non-grafted and grafted groups. For repeated measure binary outcomes, generalized estimating equations (GEEs) was used. T-test, chi-square test or Wilcoxon-Man-Whitney test, as appropriate, was used to analyze all the other iii non-repeated data. Spearman’s correlation coefficient was used for correlation analyses. Results: 24 patients (49±4 years; 12 males; single implant site; 9 non-grafted cases) completed the study. Clinical healing was uneventful in all cases. Soft tissue closure over the implant was slower in grafted group (p<0.01 between groups). Wound fluid volume increase was more persistent in grafted sites, peaking at 3 (p<0.01) and 6 days (p=0.04), compared to non-grafted sites (peak at 6 days; <0.01). Both groups reached baseline GCF levels by 9 days. In grafted group only, thin tissue biotype was correlated with higher wound fluid production (r=0.4, p=0.03). Blood perfusion decreased significantly immediately postoperatively in both groups (p<0.01 within both groups). At 3 days the blood perfusion recovery was 57% and 42% in the non grafted and the grafted group, respectively. Although non-grafted sites had a 4-month recovery level comparable to 3 days post-op (p>0.05), grafted sites remained relatively ischemic at 4 months (p<0.01). 56% of sites were initially diagnosed as thin biotype. Mean ISQ increased from 69±4 and 69±1 to 72±3 and 74±2 in non-grafted and grafted sites, respectively (p<0.01 in grafted group only). Initial buccal bone thickness for non-grafted and grafted sites was 1.52±0.05 mm (1.3-1.6 mm) and 1.78±0.1 mm (1.5-2.1 mm), respectively. At 4 months, mean loss of 0.09±0.008 mm (0.06-0.1 mm) and 0.3±0.06 mm (0.1-0.5 mm) was evident in non-grafted and grafted sites, respectively (p<0.01, between groups). Thick soft tissue biotype was correlated with less buccal bone thickness loss at the apical 10- iv 12mm along the implant length in both groups (r=0.8, p=0.03). 13 CBCT records following post-tooth extraction and bone regeneration procedures were collected. Linear distance measurements from the surgical stent to ridge revealed - 0.75 ± 0.24 mm buccal bone loss in SP and - 0.97 ± 0.16 mm buccal bone loss in GBR group, respectively. Mean 3-D bone volume changes, determined by using adjacent teeth as standardization points and subtracting buccal half of the ridge for calculations, revealed volumetric bone loss of – 0.22 ± 0.08 cm3 and – 0.33 ± 0.07 cm3 in SP and GBR groups, respectively (p=0.05 between groups). Conclusion: Post-implant placement early wound healing in grafted sites is characterized by a continuous ischemic response and a higher inflammatory clinical healing profile compared to less surgically manipulated non-grafted sites. However, despite surgical trauma, buccal bone thickness loss is minimal at both grafted and non-grafted sites and consistent with previously reported bone thickness loss after flap elevation. Computerized volumetric evaluation and automatic selection of the areas of interest following CBCT image superimposition allow for better evaluation of bone changes compared to manual area selection as long as radiation exposure and dental implant related artifacts can be controlled. v Dedication Dedicated to my Family, Alex and my Teachers vi Acknowledgments I would like to express my gratitude to Dr. Binnaz Leblebicioglu for her passion, guidance and care while introducing me to clinical research and teaching me how to develop research protocols and analyze data. I would like to thank Dr. Dimitris Tatakis for his devotion to this project, help with ideas for data analysis and support with abstract corrections and competitions. I would also like to acknowledge Dr. Barbaros Selnur Erdal for his help with the CBCT part of the study. I would like to express my sincere appreciation to Dr. Mutlu Demirer for his tireless effort, ideas and time with the CBCT analysis of this project. I wish to thank Dr. Eubank for his generous assistance with the cytokine analysis in his lab and Dr. Brian L. Foster for his insightful guidance with biopsy analysis and for providing his lab facility space and equipment. I would also like to thank Dr. Lamees Alssum for training me for the clinical measurements of the study, Michael Chaves and Michelle Tan for helping me with lab work and Debbi Pack for taking the CBCTs in the Radiology Clinic. Furthermore, I would like to thank all the Graduate Periodontal Residents for their support with recruitment. The study was supported by intramural (OSU COD) and extramural (AAIDF) grants to Dr. Binnaz Leblebicioglu. vii Vita 2013…………… Doctor of Dental Surgery, National & Kapodistrian University of Athens, Greece 2014…………………………………………………………………………Private Practice Employment 2015-2018…………………… Post-doctoral Training in Periodontics, The Ohio State University, The Ohio State University, Columbus, Ohio, USA Peer-reviewed abstracts § CBCT analysis of post-surgery buccal bone thickness Leblebicioglu B., Kofina V., Demirer M., Alssum L., Erdal B.S., Yildiz V.O., Tatakis D.N. Poster accepted at EuroPerio9, Amsterdam, The Netherlands – 06/20/2018 - 06/23/2018 § Bone grafting and post-implant surgery flap blood perfusion rate Kofina V., Demirer M., Alssum L., Erdal B.S., Yildiz V.O., Tatakis D.N., Leblebicioglu B. Poster at 2018 AADR/CADR, Fort Lauderdale, FL, USA – 03/24/2018 § Buccal bone thickness in relation to flap blood perfusion and implant stability viii Kofina V., Demirer M., Alssum L., Erdal B.S., Yildiz V.O., Tatakis D.N., Leblebicioglu B. Oral presentation at 2018 Midwest Society of Periodontology Graduate Student Research Forum (1st Honorary Mention), Chicago, IL, USA – 2/24/2018 § CBCT analysis of alveolar bone remodeling following regenerative surgery Kofina V., Alssum L., Erdal B.S., Yildiz V.O., Tatakis D.N., Leblebicioglu B. Poster at Research Day of COD at OSU, 10th Annual Translational to Clinical Regenerative Medicine Wound Care Conference, Columbus, OH, USA – 02/28/2017 & 03/10/2017 and 2017 IADR/AADR/CADR, San Francisco, CA, USA – 03/24/2017 § Potential risk predictors for peri-implant diseases: An observational prospective study Heming Z., Kofina V., Sakulpaptong W., Yildiz V.O., Tatakis D.N., Leblebicioglu B. Poster at Research Day of COD at OSU, Columbus, OH, USA – 02/28/2017 & 2017 IADR/AADR/CADR, San Francisco, CA, USA – 03/24/2017 § Modified periodontal indices and peri-implant diagnosis Barriere T., Sakulpaptong W., Kofina V., Yildiz V.O., Tatakis D.N., Leblebicioglu B. Poster at Research Day of COD at OSU, Columbus, OH, USA – 02/28/2017 & 2017 IADR/AADR/CADR, San Francisco, CA, USA – 03/24/2017 ix Table of contents Abstract .............................................................................................................................................................