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

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.