Platelet-Derived Growth Factors to Enhance Healing and Reduce Post-Extraction Complications in Smokers
Phase: NA
Conditions: Smoke Exposure
Sponsor: King Abdulaziz University

Cover Letter 
01-18-2026
Protocol Registration and Results System (PRS) 
Title of Study: 
Platelet-Derived Growth Factors to Enhance Healing and Reduce Post-Extraction 
Complications in Smokers
Dear PRS Review Team, 
We are pleased to submit the study protocol entitled “Application of Growth Factors 
Derived from Platelets to Accelerate Healing and Reduce Post-Extraction 
Complications in Smokers: A Randomized Clinical Trial” for registration in the 
Protocol Registration and Results System (PRS). 
This submission presents a prospective, randomized, split-mouth clinical trial 
protocol to be conducted at the Faculty of Dentistry, King Abdulaziz University, Jeddah, 
Saudi Arabia. The study aims to evaluate the effectiveness of Advanced Platelet-Rich 
Fibrin (A-PRF) in enhancing soft-tissue healing following tooth extraction in smokers, 
a population known to be at increased risk of delayed wound healing and postoperative 
complications. 
The manuscript has been prepared exclusively as a protocol, written entirely in the 
future tense, and does not include any results, discussion, or conclusions. The 
document ends with a clearly defined statistical analysis plan, in full compliance with 
PRS and clinical trial registration requirements. Ethical approval for this study has been 
obtained from the Research Ethics Committee of the Faculty of Dentistry, King 
Abdulaziz University, and all study procedures will be conducted in accordance with the 
principles of the Declaration of Helsinki. 
Registration of this protocol will enhance research transparency, support reproducibility, 
and contribute valuable evidence toward improving postoperative care strategies for 
smokers undergoing dental extractions. 
Thank you for your time and consideration of our submission. Please do not hesitate to 
contact us should further information or clarification be required. 
Sincerely, 
Dr. Amal Ghazi Jamjoom 
Department of Periodontics 
Faculty of Dentistry 
King Abdulaziz University 
Jeddah, Saudi Arabia 

Platelet-Derived Growth Factors to Enhance Healing and Reduce Post-
Extraction Complications in Smokers (Study Protocol) 
Abstract 
Smoking is a well-established risk factor for impaired wound healing following dental 
extractions due to its vasoconstrictive, hypoxic, and immunosuppressive effects. These 
alterations increase the risk of postoperative complications, including delayed soft-tissue 
healing, infection, and alveolar osteitis. Advanced Platelet-Rich Fibrin (A-PRF) is an 
autologous biomaterial rich in growth factors that promotes angiogenesis, collagen 
synthesis, and tissue regeneration. This study protocol describes a randomized, split-mouth 
clinical trial to evaluate the effectiveness of A-PRF in enhancing soft-tissue healing and 
reducing post-extraction complications in smokers. Adult smokers requiring bilateral 
simple tooth extractions will be recruited from King Abdulaziz University Dental Hospital. 
One extraction socket will receive A-PRF, while the contralateral socket will heal naturally 
and serve as the control. Soft tissue healing will be assessed using standardized digital 
intraoral scans at baseline, 7 days, and 14 days post-extraction. Patient-reported outcomes 
related to pain and interference with daily activities will also be collected. The findings of 
this study are expected to contribute to evidence-based strategies for improving 
postoperative healing outcomes in smokers. 
Keywords 
Advanced Platelet-Rich Fibrin; Smoking; Tooth Extraction; Wound Healing; Growth Factors 
1. Introduction
Wound healing following oral surgical procedures is a complex biological process involving 
hemostasis, inflammation, proliferation, and tissue remodeling. These phases require 
adequate blood supply, oxygenation, immune competence, and cellular activity to proceed 
normally. Smoking has been shown to significantly disrupt these mechanisms, resulting in 
delayed and compromised wound healing. Nicotine-induced vasoconstriction, carbon 
monoxide–related hypoxia, and smoking-associated immune suppression collectively 
impair clot formation, fibroblast function, collagen synthesis, and angiogenesis. 
Consequently, smokers are at a higher risk of postoperative complications such as delayed 
healing, infection, and alveolar osteitis following tooth extraction. 
Advanced Platelet-Rich Fibrin (A-PRF) is a second-generation platelet concentrate obtained 
from autologous blood without the use of anticoagulants. It acts as a biological scaffold that 
gradually releases key growth factors, including platelet-derived growth factor, 
transforming growth factor-beta, and vascular endothelial growth factor, over an extended 
period. These properties support neovascularization, fibroblast migration, epithelialization, 
and soft tissue regeneration. Due to its autologous nature and sustained biological activity, 
A-PRF represents a promising adjunctive therapy for enhancing healing in patients with 
compromised regenerative capacity, such as smokers.

While the benefits of platelet-rich fibrin have been demonstrated in healthy populations, 
evidence regarding its effectiveness in smokers remains limited. Given the increased 
prevalence of smoking-related oral surgical complications, there is a clinical need to 
investigate regenerative strategies that may mitigate the negative effects of tobacco use. 
This study protocol outlines a randomized, split-mouth clinical trial designed to evaluate 
the effect of A-PRF on soft tissue healing following tooth extraction in smokers. 
2. Materials and Methods
2.1 Study Design 
This study will be designed as a randomized, controlled clinical trial with a split-mouth 
design. Each participant will require bilateral simple tooth extractions and will serve as 
their own control. One extraction socket will be randomly allocated to receive A-PRF, while 
the contralateral socket will heal naturally. 
2.2 Study Setting 
The study will be conducted at the Faculty of Dentistry and University Dental Hospital, King 
Abdulaziz University, Jeddah, Saudi Arabia. 
2.3 Study Population 
Participants will include adult smokers aged 18 years or older who require bilateral simple 
tooth extractions. Eligible participants must be active cigarette smokers consuming at least 
10 cigarettes per day. 
2.4 Inclusion and Exclusion Criteria 
Inclusion criteria will include adults aged 18 years or older, active cigarette smokers, and 
patients requiring bilateral simple extractions. Exclusion criteria will include patients with 
systemic diseases affecting healing, bleeding disorders, pregnancy or lactation, and use of 
tobacco products other than conventional cigarettes. 
2.5 Randomization and Allocation 
Randomization will be performed using a sealed-envelope technique. One extraction site 
will be randomly assigned to receive A-PRF, while the contralateral site will serve as the 
control. Allocation concealment will be maintained until the time of intervention. 
2.6 Intervention 
Advanced Platelet-Rich Fibrin will be prepared immediately before extraction using 
autologous venous blood centrifuged at 2700 rpm for 13 minutes. The resulting fibrin clot 
will be compressed, placed into the designated extraction socket, and stabilized with figure-
of-eight sutures. Control sites will receive suturing only. 
2.7 Outcome Assessment 
Soft tissue healing will be assessed by measuring the socket area using digital intraoral 
scanning at baseline, 7 days, and 14 days post-extraction. Patient-reported outcomes will be 

collected using an electronic questionnaire assessing pain intensity and interference with 
daily activities. 
2.8 Statistical Analysis 
Descriptive statistics will be used to summarize the data. Normality will be assessed using 
the Shapiro–Wilk test. Due to the split-mouth design and expected non-normal distribution, 
comparisons between intervention and control sites will be performed using the Wilcoxon 
signed-rank test. A p-value < 0.05 will be considered statistically significant.