Use of cells and/or biologics combined with scaffolds for soft tissue regeneration around dental implants

Abstract

Abstract Background The aim of this systematic review is to evaluate the efficacy of cell‐based therapies and biologically enhanced scaffolds for peri‐implant soft tissue regeneration, including the increase in soft tissue thickness (STT) and/or keratinized mucosa (KM) augmentation. Methods A systematic literature search was conducted in Ovid MEDLINE, EMBASE, and Dentistry and Oral Sciences Source until August 2025. A focused question was developed: “In patients with soft tissue defects requiring soft tissue augmentation procedures prior to, at the time of implant placement or after it, what is the efficacy of combining cell therapy and/or biological treatments with a soft tissue scaffold compared to the use a soft tissue scaffold without cells and/or biologics, or no scaffold, on the increase of STT and/or KM in clinical trials or prospective case series?”. Post‐operative morbidity, interproximal bone level changes, clinical peri‐implant outcomes or patient‐reported outcome measures (PROMs) were collected. Risk of bias was assessed using RoB 2.0, ROBINS‐I and the National Institutes of Health (NIH) Study Quality Assessment Tool. Results Ten publications were included (six randomized clinical trials [RCTs] and four prospective case series). The use of free gingival grafts (FGGs) lead to significantly greater KM augmentation when compared with platelet‐rich fibrin (PRF) membranes (weighted mean difference [WMD] = −2.0; 95% confidence interval [CI]: −3.3, −0.8; p < 0.001) although PRF membranes significantly increased the amount of KM when compared to no scaffold/graft (n = 2; WMD = 1.1 mm; 95% CI: 0.2, 2.1; p = 0.017) and seem to increase also STT. Available data on other biologics (e.g., recombinant human platelet‐derived growth factor BB [rhPDGF‐BB]) are scarce. No studies evaluating cell therapies were identified. Conclusions PRF membranes are effective in increasing the KM and STT around dental implants, even if KM augmentation by means of autogenous grafts lead to superior outcomes. There is a lack of evidence on cell‐based therapies or other biologics for their use in soft tissue regeneration around dental implants.