Platelet Rich Fibrin Treatment for the Alveolar Ridge Preservation in Smokers

* This study will be conducted according to the principles outlined in the Declaration of Helsinki regarding experiments on human beings. This work was submitted and approved by the Ethics and Scientific Committee, approval number ID170706007.
* Participant selection: Volunteers must agree to participate in the study after signing an informed consent (previously approved by the Ethics Committee). Participants will be treated at the Dental Clinical School of Dentistry at the Pontificia Universidad Católica de Chile or in the Dentistry/ Health Sciences Center at San Bernardo from the University of the Andes, Chile. Both institutions are located in Santiago, Chile.

Diagnosis and evaluation before interventions: Volunteer participants will be selected after a clinical and periapical radiographic examination to establish the need for tooth extraction. Laboratory tests, including a complete blood coagulation profile, will be required for all volunteers. Finally, a salivary cotinine test will ensure the smoker's condition.

* Randomization: A random number will be assigned to all participants. An independent research team member will establish a randomization sequence without contact with the clinician's team. Sealed envelopes with randomization will be performed and opened by surgeons before the tooth extraction.
* First Intervention: Participants assigned to the experimental group will be treated with L-PRF plugs and membranes from venous blood. Participants will have drawn blood after venipuncture (median cubital vein) into sterile, glass-coated plastic 9 mL tubes without anticoagulant. These tubes will be centrifuged at 2700 rpm for 12 min (Relative Centrifugal Forces-clot = 408 g). After tooth extraction, participants in the experimental group will be treated with L-PRF plugs and membranes, and the control group will be sutured. Participants in both groups will be intraoral scan and intraoral scan and Cone Beam Computed Tomography in the treated zone. Clinicians will make a post-surgical control to evaluate how healing will be performed.
* Second Intervention: Four months after the first Intervention, participants will recall getting a second scan and Cone Beam Computed Tomography in the treated zone. Images will be used for implant treatment planification. Before implant placement, a biopsy (2 mm in diameter) will be taken. The biopsy will be analyzed by Micro-computed tomography and decalcified and included in paraffin for histological sections.
* The primary outcome variable established will be radiographic linear changes in horizontal width and vertical height of the alveolar ridge measured in the CBCTs taken immediately after tooth extraction and after four months. Secondary outcomes included the changes in ridge contours and volume estimated from the intraoral scan images.
* Data analysis: Members of the research team who do not know the group intervention of the participants will determine alveolar ridge height and width in oral scans and CBCTs taken in the first and second Interventions. As such, micro-CT analysis and histological sections will be analyzed.
* Statistical analysis The results will express the mean ± 95% CI. Will be considered as significant differences when P < 0.05. Nominal data will be evaluated.

• Autologous Leukocyte and platelet-rich fibrin (Other): Participants will be treated with L-PRF plugs and membranes from autologous venous blood. Participants will have drawn blood after venipuncture (median cubital vein) into sterile, glass-coated plastic 9 mL tubes without anticoagulant. These tubes will be centrifuged at 2700 rpm for 12 min (Relative Centrifugal Forces-clot = 408 g). After tooth extraction, participants in the experimental group will be treated with L-PRF plugs and membranes.
• Intraoral Scan (Other): Intraoral scan will be taken in the treated zone after tooth extraction and after four months.
• Computed Tomography (Radiation): Cone Beam Computed Tomography in the treated zone will be taken after tooth extraction and after four months.
• Biopsy (Other): Before dental implant placement, a biopsy (2 mm in diameter) will be taken. The biopsy will be analyzed by Micro-computed tomography and decalcified and included in paraffin for histological sections.

Primary outcomes

• Alveolar ridge changes [inmediately after tooth extraction and after four months]: linear changes in horizontal width and vertical height of the alveolar ridge measured in the CBCTs taken immediately after tooth extraction and after four months.

Secondary outcomes

• Alveolar ridge sof tissue changes [inmediately after tooth extraction and after four months]: changes in ridge contours and volume estimated from the intraoral scan images
• Tissue healing [Biopsy at least four months after tooth extraction]: Tissue analysis by Micro-CT and histological sections.

Sex: All, ages: 20 Years to 70 Years, accepts healthy volunteers

Inclusion Criteria:

Smokers (at least five cigarettes/day) have had the habit for at least one year.

* treatment plan that includes the indication of extraction of a single, double-rooted, or multi-rooted tooth and prosthetic rehabilitation with osseointegrated implants
* Patients with controlled systemic pathologies (hypertension, diabetes, hypercholesterolemia).
* With alveolar bone support of at least 50% and whose indication is delayed implant placement at least four months after extraction.
* Periapical lesions of no more than 5 mm diameter.

Exclusion Criteria:

* patients taking immunosuppressive or anticoagulant drugs
* pregnant
* users of removable prostheses
* Individuals with altered values of platelet count or coagulation parameters.

• Constanza Martínez, DDS PhD, Principal investigator, University of the Andes, Chile