Influence of Timing of Implant Placement on Early Healing Molecular Events

Inclusion Criteria:

• Age ≥25 years old

• Good/controlled medical and psychological health

• Good oral hygiene (FMPS≤20%)

• Presence of a tooth in the aesthetic region (from incisor to second premolar) inneed of extraction and further oral rehabilitation with a single dental implant.

• For the IP group, the extraction socket should fulfil the following parameters, asdescribed by the 5th ITI consensus [46]: intact socket wall; facial bone wall ≥1mmin thickness; no acute infection at the site; availability of bone apical andpalatal to the socket to provide primary stability.

• At least one neighbouring natural tooth.

• A functional occlusion with a minimum of four occlusal units (i.e., pairs ofoccluding posterior teeth).

• Willingness to read and sign a copy of the Informed Consent Form (ICF) after readingthe Patient Information Sheet (PIS), and after the nature of the study has beenfully explained and potential questions fully answered.

Exclusion Criteria:

• Any known systemic disease severely affecting bone metabolism (e.g., Cushing'ssyndrome, Crohn's disease, rheumatoid arthritis, osteoporosis or diabetes type I anduncontrolled diabetes type II).

• Self-reported HIV or viral hepatitis.

• Self-reported alcoholism or chronic drug abuse.

• Smokers (including current smokers or former smokers who had quit for < 3 months);patients reporting use of vape/e-cigarettes will also be excluded.

• Self-reported pregnancy or lactation (this criterion is due to oral tissue changesrelated to pregnancy and nursing, which can affect interpretation of study results).

• Chronic treatment (i.e., 2 weeks or more) with any medication known to affect oralstatus or bone metabolism (e.g., bisphosphonates, hormone replacement therapy,immunosuppressants) within 1 month before baseline visit.

• Chronic treatment with anticoagulants (including Aspirin), corticosteroids,immunosuppressants or other medications that may influence blood coagulation/count.

• Antibiotic or anti-inflammatory therapy during the month preceding the baselineexam.

• Untreated caries lesions and untreated/uncontrolled periodontal disease; If patientsrequire periodontal treatment (non-surgical and/or surgical), this will be arrangedoutside the study protocol and completed prior to enrolment;

• Inadequate keratinized tissue width (<2 mm) in the mid-buccal aspect of the area tobe treated in the study.

• Physical handicaps that would interfere with the ability to perform adequate oralhygiene in the area of implant placement.

• Patients requiring maxillary sinus lift surgery before implant placement.

• Self-reported bruxism.

• Patients not willing to receive animal-derived biomaterials for GBR.

• Patients suffering from a known psychological disorder or with limited mentalcapacity or language skills such that study information could not be understood,informed consent could not be obtained, or simple instructions could not befollowed.

• Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with trial participation or mayinterfere with the interpretation of trial results and, in the judgement of theinvestigator, would make the subject inappropriate for entry into this trial.