Immediate Implant Placement With Subepithelial Connective Tissue Grafting and Probiotics

Comparative Evaluation of Platelet-Rich Fibrin Versus Probiotics as Adjuncts to Immediate Implant Placement Combined With Subepithelial Connective Tissue Grafting: Clinical, Biological, and Radiographic Peri-Implant Tissue Outcomes A Parallel-Arm Randomized Trial

The present study aims to evaluate and compare the clinical, radiographic, and biological peri-implant tissue outcomes of platelet-rich fibrin versus probiotics as adjuncts to immediate implant placement combined with subepithelial connective tissue grafting in adults requiring single immediate implant placement.

Study Overview

• Status: Not yet recruiting
• Conditions: Dental Implant Failed
• Intervention / Treatment: Procedure: Platelet-Rich Fibrin; Procedure: Probiotics

Detailed Description

Dental implant therapy in the esthetic zone is currently judged not only by implant survival but also by preservation of peri-implant hard and soft tissues, maintenance of facial mucosal stability, and achievement of acceptable esthetic outcomes. Immediate implant placement is attractive because it may shorten treatment time, reduce the number of surgical procedures, and preserve the restorative pathway. Nevertheless, immediate placement does not eliminate the physiologic remodeling that follows tooth extraction, particularly at the facial aspect of the socket. Recent evidence has shown that even when immediate implants are successfully integrated, post-extraction dimensional changes may still compromise mucosal contour, midfacial level, and long-term esthetic integration.

Because implant timing alone cannot fully prevent hard- and soft-tissue alteration, contemporary immediate implant therapy increasingly incorporates peri-implant tissue augmentation procedures. Among these, peri-implant soft-tissue augmentation has become an important component of treatment planning because it may improve tissue volume, phenotype, and esthetic stability. Current evidence also indicates that autogenous grafts generally provide more favorable peri-implant soft-tissue augmentation outcomes than substitute materials. In parallel, adequate keratinized mucosa continues to be associated with better peri-implant clinical conditions and lower risk of peri-implant disease, highlighting the importance of peri-implant soft-tissue quality as both an esthetic and biologic determinant of treatment success. Additional systematic evidence has further supported the positive relationship between keratinized mucosa and peri-implant health and stability.

Within this context, subepithelial connective tissue grafting has become a key strategy for enhancing peri-implant mucosal thickness and supporting facial mucosal stability around immediate implants. Randomized clinical evidence has shown that connective tissue grafting performed with single immediate implants in the maxillary esthetic zone can improve mid-buccal mucosal stability over long-term follow-up. Other randomized data have also demonstrated favorable esthetic and peri-implant tissue outcomes when soft-tissue grafting is incorporated into immediate implant protocols. More recent volumetric clinical findings have reinforced the importance of peri-implant soft-tissue volume in limiting unfavorable midfacial mucosal alterations after immediate implant placement.

Although subepithelial connective tissue grafting is an established soft-tissue approach, interest has grown in adjunctive biologic interventions that may further enhance wound healing and peri-implant tissue maturation. Platelet-rich fibrin has received considerable attention because it is an autologous fibrin matrix rich in platelets, leukocytes, and growth factors that may promote angiogenesis, fibroblast proliferation, soft-tissue healing, and early tissue remodeling. Recent clinical evidence has shown that leukocyte-platelet-rich fibrin may improve peri-implant mucosal dimensions and soft-tissue enhancement around implants. In addition, systematic review and meta-analytic evidence suggest that injectable platelet-rich fibrin can positively influence gingival phenotype modification, supporting its biologic plausibility as an adjunctive soft-tissue enhancer.

At the same time, probiotics have emerged as a potentially valuable adjunct in implant dentistry because of their capacity to regulate the oral microbiome, modulate inflammatory pathways, and influence host immune balance. Recent evidence has suggested that probiotics may promote bone homeostasis, facilitate tissue regeneration, and reduce peri-implant inflammatory burden through control of dysbiosis and host modulation. Systematic review evidence in peri-implant oral diseases has shown that probiotic therapy may improve certain clinical and inflammatory parameters, although the available data remain heterogeneous and not yet definitive. More recent meta-analytic findings have similarly indicated that probiotics may provide adjunctive benefits in peri-implant disease management, while also confirming the need for further well-designed trials.

Beyond clinical and esthetic evaluation, biologic monitoring has become increasingly important in peri-implant research. Peri-implant crevicular fluid biomarkers may provide insight into inflammatory activity and tissue remodeling before overt clinical breakdown becomes evident. Among these biomarkers, matrix metalloproteinase-8 has attracted particular attention because it is closely associated with collagen degradation and peri-implant inflammatory activity, making it one of the most relevant biologic markers for assessing peri-implant tissue breakdown.

Despite the expanding literature on immediate implant placement, peri-implant soft-tissue grafting, platelet-rich fibrin, probiotics, and biomarker-based peri-implant assessment, there is still no clear randomized clinical evidence directly comparing platelet-rich fibrin and probiotics as adjuncts to immediate implant placement combined with subepithelial connective tissue grafting. Therefore, the rationale of the present study is to evaluate whether these two biologically distinct adjunctive approaches differ in their clinical, radiographic, and biologic effects on peri-implant tissue outcomes, thereby helping to optimize peri-implant tissue management in immediate implant therapy.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: walid elamrousy, Phd; Phone Number: 01029552024; Email: waled_hammed@den.kfs.edu.eg
• Study Contact Backup: Name: Lamis OMER, bachelor; Phone Number: +249999005524; Email: nour_hetata@den.kfs.edu.eg

Study Locations

• Egypt
  • Kafrelsheikh
    • Kafr ash Shaykh, Kafrelsheikh, Egypt, 214312
      • faculty of dentistry, kafrelsheikh University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 20 to 45 years.
• Systemically healthy patients eligible for implant surgery.
• Patients requiring extraction of a single non-restorable tooth indicated for immediate implant placement.
• Implant sites located in the maxillary esthetic or para-esthetic zone.
• Sites with sufficient apical and/or palatal bone to permit correct three-dimensional implant positioning and achieve adequate primary stability.
• Sites suitable for simultaneous subepithelial connective tissue grafting.
• Patients with acceptable oral hygiene and good compliance with periodontal and implant treatment.
• Patients willing to attend all follow-up visits and comply with study instructions.

Exclusion Criteria:

• Medically compromised patients or patients with systemic conditions that may contraindicate implant surgery or interfere with healing.
• Smokers.
• Pregnant or lactating women.
• Patients with uncontrolled periodontal disease or poor oral hygiene.
• Patients with acute infection at the intended implant site.
• Patients with insufficient bone volume preventing immediate implant placement with adequate primary stability.
• Patients with a history of head and neck radiotherapy or chemotherapy.
• Patients receiving bisphosphonates or other medications known to affect bone metabolism or soft tissue healing.
• Patients with parafunctional habits that may jeopardize implant stability or restorative success.
• Patients unwilling or unable to complete the follow-up period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: platelet-rich fibrin group; Immediate implant placement with subepithelial connective tissue grafting and adjunctive platelet-rich fibrin	Procedure: Platelet-Rich Fibrin; platelet-rich fibrin will be prepared immediately before application using freshly drawn autologous venous blood and a standardized centrifugation protocol selected according to the equipment available in the study setting. The prepared PRF will be used as an adjunct to the immediate implant and subepithelial connective tissue grafting procedure according to the finalized protocol, either locally around the peri-implant site and/or in intimate relation to the grafted soft tissue to enhance healing and tissue maturation.
Experimental: probiotics group; Immediate implant placement with subepithelial connective tissue grafting and adjunctive probiotics	Procedure: Probiotics; Probiotics probiotics will be administered as an adjunct to the immediate implant and subepithelial connective tissue grafting The mode of delivery, dose, and duration will be standardized for all patients allocated to this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of matrix metalloproteinase-8 (MMP-8) levels	Biological assessment will be performed by collecting peri-implant sulcular fluid samples for evaluation of matrix metalloproteinase-8 (MMP-8) levels. After gentle removal of supragingival plaque, the peri-implant site will be isolated with cotton rolls and dried with mild air flow. Sterile PerioPaper strips will be inserted carefully into the peri-implant sulcus until slight resistance is encountered and left in place for 30 seconds. Any strip contaminated with blood or saliva will be discarded. The collected samples will be transferred to sterile Eppendorf tubes and stored until analysis. Quantitative assessment of MMP-8 will be carried out using a human MMP-8 ELISA kit according to the manufacturer's protocol.	12-months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Principal Investigator: walid elamrousy, phd, Kafrelsheikh University

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2026
• Primary Completion (Estimated): May 20, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Probiotics
• Other Study ID Numbers: KFSIRB200-1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: upon request
• IPD Sharing Time Frame: 12 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No