_Applied_  
_sciences_  
_Article_  
**Factors Affecting the Outcome of Periapical Surgery;**  
**a Prospective Longitudinal Clinical Study**  
**[PERSON] 1,2,*(r), [PERSON] 3,4, [PERSON] 4, [PERSON] 5, [PERSON] 6, [PERSON] 7,8 and [PERSON] 8,9(r)  
1 Department of Operative Dentistry and Institute of Biomedical Sciences, Dow University of Health Sciences, Karoachi 74200, Pakistan  
2 Department of Restorative Dentistry and Endodontics, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia  
3 Department of Surgery, Aga Khan University, Karoachi 74800, Pakistan; [EMAIL_ADDRESS]  
4 Department of Biological and Biomedical Sciences, Aga Khan University, Karoachi 74800, Pakistan; [EMAIL_ADDRESS]  
5 Department of Pathology, [PERSON] Institute of Oral Health Sciences, Dow University of Health Sciences, Karoachi 74200, Pakistan; [EMAIL_ADDRESS]  
6 Department of Conservative Dental Sciences, College of Dentistry, Prince Sattam Bin Abdulaziz University, Al-Khaar 11942, Saudi Arabia; [EMAIL_ADDRESS]  
7 Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia; [EMAIL_ADDRESS]  
8 Engineer [PERSON] Research Chair for Dental and Oral Rehabilitation (Department), College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia; [EMAIL_ADDRESS]  
9 Department of Restorative Dentistry--Operative Division, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia  
10 Correspondence: [EMAIL_ADDRESS]; Tel. : +96-65-8167-4914  
**Clitation:** [PERSON]; [PERSON] [PERSON]; [PERSON]; [PERSON] [PERSON]; [PERSON]; [PERSON] [PERSON]; [PERSON] [PERSON] Factors Affecting the Outcome of Periapical Surgery; a Prospective Longitudinal Clinical Study. _Appl. Sci._**2021**, _11_, 11768. [[https://doi.org/10.3390/appl12411768](https://doi.org/10.3390/appl12411768)]([https://doi.org/10.3390/appl12411768](https://doi.org/10.3390/appl12411768))  
**Publicisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. **C0 Copyright:** (c) 2021 by the authors. License MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([[https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)]([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/))). **1. Introduction**  
The treatment of choice for symptomatic, persistent or enlarging periapical lesion after conventional re-root canal treatment is surgical endodontic treatment, which is aimed at resecting the root end and then creating a barrier at the apical end of the root with an inert material [1, 2, 3]. The goal of this treatment protocol is to salvage the tooth and prevent it from further damage by limiting the entry of microbes and their byproducts into the canal system, thus promoting the health of the tooth. The success of surgical endodontic treatment mainly relies on the absence of clinical signs and symptoms and radiographic resolution of periapical lesions. Studies have shown that multiple factors may influence the outcome of periapical surgery such as age, gender, smoking, type of root-end filling material, size of the preoperative periapical lesion, and the presence of pretreatment signs and symptoms [3; 4]. Smoking is considered one of the risk factors that can impede periapical healing. Smoking disturbs healing by limiting the supply of oxygenated blood and nutrients to the periapical area [5]. This in turn makes periapical tissue more susceptible to bacterial infection [6]. Additionally, it alters the synthesis of collagen, expedites bone loss, and interferes in the tissue repair process around the periapical area [7; 8]. Furthermore, smokers have restricted defense mechanisms due to the deficiency of several immunological factors such as Tumor necrosis factor alpha (TNF-\(\alpha\)) and Human beta defensin-2 (hBD-2) [9].