Dental implants have been on the market for several years and they are routinely used to replace single/multiple missing teeth with a high success rate. However, there is still a limited number of studies comparing the influence of timing of implant placement on wound healing. In addition, there is no data available on the signaling pathways and the expression of healing biomarkers involved in the early stages of osseointegration after immediate implant placement (IP) or delayed implant placement (DP).

The primary objective of this study is to describe changes in the expression of inflammatory, angiogenesis and osseous biomarkers of saliva at 1, 3, 7, 15 and 30 days and of PICF at 3, 7, 15 and 30 days after immediate implant placement (IP) compared with delayed placement (DP).

This is a two-centre prospective, parallel-group pilot study which will consist of 10 to 11 visits over a minimum period of 16 months. The study will take place at the Centre for Oral Clinical Research (COCR), at the Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (main centre), United Kingdom and at the Implant Research Centre, School of Dental Medicine, University of Belgrade, in accordance with local guidelines and procedures/ interventions detailed below.

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) in need of extraction and further oral rehabilitation with a single dental implant.
• For the IP group, the extraction socket should fulfil the following parameters, as described by the 5th ITI consensus [46]: intact socket wall; facial bone wall ≥1mm in thickness; no acute infection at the site; availability of bone apical and palatal 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 of occluding posterior teeth).
• Willingness to read and sign a copy of the Informed Consent Form (ICF) after reading the Patient Information Sheet (PIS), and after the nature of the study has been fully explained and potential questions fully answered.

Exclusion Criteria:

• Any known systemic disease severely affecting bone metabolism (e.g., Cushing's syndrome, Crohn's disease, rheumatoid arthritis, osteoporosis or diabetes type I and uncontrolled 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 changes related 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 oral status 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 baseline exam.
• Untreated caries lesions and untreated/uncontrolled periodontal disease; If patients require periodontal treatment (non-surgical and/or surgical), this will be arranged outside the study protocol and completed prior to enrolment;
• Inadequate keratinized tissue width (<2 mm) in the mid-buccal aspect of the area to be treated in the study.
• Physical handicaps that would interfere with the ability to perform adequate oral hygiene 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 mental capacity or language skills such that study information could not be understood, informed consent could not be obtained, or simple instructions could not be followed.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgement of the investigator, would make the subject inappropriate for entry into this trial.