Application of Growth Factors Derived From Platelets to Accelerate Healing and Reduce Post-extraction Complications in Diabetic Individuals
Phase: NA
Conditions: Diabete Mellitus
Sponsor: King Abdulaziz University

 
Cover Letter – Protocol Registration and Results System (PRS) 
Date: Dec.13.2025 
To: 
Protocol Registration and Results System (PRS) Review Team 
Subject: Protocol Registration Submission 
Dear PRS Review Team, 
We respectfully submit the study protocol entitled “Application of Growth Factors Derived 
from Platelets to Accelerate Healing and Reduce Post-extraction Complications in Diabetic 
Individuals” for registration in the Protocol Registration and Results System (PRS). 
This protocol describes a randomized, double-blinded, split-mouth clinical trial that will be 
conducted at King Abdulaziz University Dental Hospital. The study is designed to evaluate the 
effect of Advanced Platelet-Rich Fibrin (A-PRF) on post-extraction soft tissue healing in 
patients with diabetes mellitus, a population known to exhibit impaired wound healing and 
increased susceptibility to postoperative complications. 
The study will enroll adult diabetic patients requiring bilateral extraction of the same tooth type. 
One extraction socket will be randomly assigned to receive A-PRF, while the contralateral socket 
will serve as a control. Healing will be assessed using digital intraoral scanning at predefined 
time points, along with patient-reported outcome measures. The split-mouth design has been 
selected to minimize inter-individual variability and improve internal validity. 
The protocol has been developed in accordance with ethical and methodological standards for 
human clinical research. Ethical approval has been obtained from the Institutional Review Board 
of King Abdulaziz University Dental Hospital, and the study will be conducted in compliance 
with the Declaration of Helsinki. Written informed consent will be obtained from all participants 
before enrollment. At the time of registration, no participants have been enrolled, and no data 
have been collected. 
This registration is being submitted to ensure transparency, methodological rigor, and 
prospective documentation of the study design and planned analyses. We confirm that the 
information provided in the PRS submission accurately reflects the study protocol and that study 
results will be reported in accordance with PRS requirements upon completion. 
Thank you for your review and consideration of this protocol registration. Please do not hesitate 
to contact us if you require any additional information or clarification. 
Sincerely, 

Dr. Amal Ghazi Jamjoom 
Principal Investigator 
King Abdulaziz University Dental Hospital 
Jeddah, Saudi Arabia 
Email: [your institutional email] 
On behalf of the study team: 
Ziyad Alsefri; Osamah Shindi; Amal Jamjoom 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Application of Growth Factors Derived from Platelets to Accelerate Healing and Reduce 
Post-Extraction Complications in Diabetic Individuals 
 
Authors 

Ziyad Alsefri*, Osamah Shindi*, Amal Jamjoom 
 
Abstract 
Introduction 
Diabetes Mellitus (DM) represents a significant global public health challenge, with a 
particularly high prevalence in Saudi Arabia. The increasing incidence of DM has raised 
concerns regarding optimal management strategies for surgical procedures such as dental 
extractions. Diabetic individuals frequently experience impaired postoperative healing due to 
compromised tissue repair mechanisms and increased susceptibility to infection. Conventional 
management approaches may be insufficient, highlighting the need for biologically driven 
adjunctive therapies. 
Objective 
This study aims to evaluate the clinical effectiveness of Advanced Platelet-Rich Fibrin (A-PRF) 
in enhancing soft-tissue healing and reducing post-extraction complications in diabetic patients. 
Methods 
A randomized, double-blinded, split-mouth clinical trial will be conducted at King Abdulaziz 
University Dental Hospital. Diabetic patients requiring bilateral extraction of the same tooth type 
will be enrolled. One extraction socket will be randomly assigned to receive A-PRF, while the 
contralateral socket will serve as the control. Healing will be assessed using digital intraoral 
scanning at baseline, 1 week, and 3 weeks post-extraction. Statistical analysis will be performed 
using paired-comparative tests, with a significance level of p < 0.05. 
Expected Outcomes 
The application of A-PRF is expected to enhance soft tissue healing and reduce postoperative 
complications in diabetic individuals. 
Conclusion 
This study is expected to provide clinical evidence supporting the use of A-PRF as a biologically 
based adjunctive approach to improve post-extraction healing outcomes in diabetic patients. 
Introduction 
Diabetes Mellitus (DM) is a global public health problem, with an especially high prevalence in 
Saudi Arabia. The rising incidence of DM has increased concerns regarding the management of 
diabetic patients undergoing surgical procedures, including tooth extractions. Diabetic 
individuals often exhibit impaired postoperative healing characterized by delayed tissue repair, 

prolonged inflammation, and an increased risk of infection. Conventional treatment strategies 
may not adequately address these challenges, necessitating the exploration of novel regenerative 
approaches. 
Platelet-derived growth factors, particularly Advanced Platelet-Rich Fibrin (A-PRF), have 
recently gained attention as potential promoters of wound healing and tissue regeneration. A-
PRF is a biologically active autologous scaffold that aligns with the physiological principles of 
wound healing by providing a sustained release of key growth factors such as platelet-derived 
growth factor (PDGF), transforming growth factor-β (TGF-β), and vascular endothelial growth 
factor (VEGF). These growth factors are essential for cellular migration, angiogenesis, and 
extracellular matrix remodeling. 
In diabetic patients, chronic hyperglycemia, prolonged inflammation, microvascular dysfunction, 
and impaired collagen synthesis contribute to delayed wound healing. The theoretical premise of 
A-PRF is that it may enhance the natural healing cascade in diabetic individuals by 
compensating for impaired biological responses. However, despite promising biological rationale 
and preliminary clinical evidence, there remains limited high-quality clinical data evaluating the 
effectiveness of A-PRF in post-extraction socket healing in diabetic patients. 
Therefore, this study will aim to evaluate the effectiveness of A-PRF in enhancing soft tissue 
healing and reducing post-extraction complications in diabetic individuals using a split-mouth 
randomized clinical trial design. The findings are expected to contribute to evidence-based 
clinical protocols and improve standards of care for diabetic patients undergoing dental 
extractions at King Abdulaziz University Dental Hospital. 
 
Research Question 
Does the application of growth factors derived from platelets accelerate healing and reduce post-
extraction complications in diabetic individuals? 
 
Research Hypotheses 
Null Hypothesis (H0): 
The application of platelet-derived growth factors will not enhance healing or reduce post-
extraction complications in diabetic individuals. 
Alternative Hypothesis (H1): 
The application of platelet-derived growth factors will accelerate healing and reduce post-
extraction complications in diabetic individuals. 
 

Objectives 
Using a split-mouth design, this study will evaluate soft tissue closure of extraction sockets by 
comparing sites treated with A-PRF to sites without A-PRF application at King Abdulaziz 
University Dental Hospital. 
 
Significance of the Study 
1. This research is expected to demonstrate the potential of A-PRF to enhance postoperative 
healing and improve the quality of life in diabetic patients undergoing dental extractions. 
2. The findings may contribute to the development of improved, biologically based 
treatment protocols for diabetic patients in dental practice. 
 
Literature Review 
Diabetes Mellitus (DM) is a complex chronic disease affecting millions worldwide, with a 
notably elevated prevalence in Saudi Arabia. The increasing incidence of DM has been attributed 
to lifestyle changes, urbanization, and genetic predisposition. Microvascular complications such 
as retinopathy, nephropathy, and neuropathy significantly increase morbidity and mortality 
among diabetic patients. 
In oral health, diabetes is associated with delayed wound healing, increased susceptibility to 
infection, periodontal disease, and tooth loss. The healing of extraction sockets normally 
progresses through distinct stages, including clot formation, inflammation, proliferation, and 
remodeling. However, in diabetic individuals, chronic hyperglycemia disrupts these processes by 
impairing angiogenesis, inflammatory regulation, collagen synthesis, and bone formation. 
Platelet-rich fibrin (PRF) has emerged as a regenerative biomaterial capable of enhancing wound 
healing through sustained growth factor release. Advanced PRF (A-PRF), produced using low-
speed centrifugation protocols, retains higher concentrations of platelets and leukocytes within a 
fibrin matrix. This biological scaffold is expected to improve cellular migration, angiogenesis, 
and tissue regeneration, making it particularly relevant for diabetic patients with compromised 
healing capacity. 
Despite promising biological mechanisms, there remains limited clinical evidence evaluating the 
specific role of A-PRF in post-extraction socket healing in diabetic patients, highlighting the 
need for well-designed randomized clinical trials. 
 

Materials and Methods 
Study Design and Ethics 
This double-blinded, randomized controlled clinical trial will be conducted at King Abdulaziz 
University Dental Hospital. Ethical approval has been obtained from the Institutional Review 
Board, and the study will be conducted in accordance with the Declaration of Helsinki (2013). 
Written informed consent will be obtained from all participants prior to enrollment. 
Sample and Study Population 
The sample size has been calculated using G*Power software with an alpha level of 0.05, 80% 
power, and a medium effect size of 0.5. Diabetic patients aged 18 years or older requiring 
bilateral extraction of the same tooth type will be recruited. Patients with systemic conditions 
other than diabetes, bleeding disorders, pregnancy, lactation, or tobacco use will be excluded. 
A split-mouth design will be employed, with one extraction site randomly assigned to receive A-
PRF and the contralateral site serving as a control. Randomization will be performed using a 
computer-generated sequence. Patients and outcome assessors will remain blinded throughout 
the study. 
Clinical Procedure 
All extractions will be performed using a standardized atraumatic technique by a single 
calibrated operator. After extraction, venous blood will be collected to prepare A-PRF using a 
low-speed centrifugation protocol. The A-PRF membrane will be placed into the assigned 
socket, while control sockets will receive no adjunctive material. All sites will be sutured using 
standardized suture material. 
Outcome Measures 
Healing will be assessed quantitatively using digital intraoral scanning at baseline, 1 week, and 3 
weeks post-extraction. Patient-reported outcomes, including pain, swelling, and satisfaction, will 
be collected using validated questionnaires at specified follow-up intervals. 
Statistical Analysis 
Data will be analyzed using Stata software (Version 16). Normality will be assessed using the 
Shapiro–Wilk test. Paired statistical tests will be used to compare healing outcomes between A-
PRF-treated and control sites, with significance set at p < 0.05.