Efficacy of biologics in root coverage and gingival augmentation therapy: An American Academy of Periodontology best evidence systematic review and network meta‐analysis

Abstract Background The aim of this systematic review was to assess the efficacy of three biologics, namely autologous blood‐derived products (ABPs), enamel matrix derivatives (EMD) and recombinant human platelet‐derived growth factor BB (rhPDGF‐BB), in root coverage and gingival augmentation therapy. Methods The protocol of this PRISMA 2020‐compliant systematic review was registered in PROSPERO (CRD42021285917). After study selection, data of interest were extracted. A network meta‐analysis (NMA) was conducted to assess the effect of different surgical interventions on the main clinical outcomes of interest (i.e., mean root coverage [MRC%], complete root coverage [CRC%], keratinized tissue width [KTW], gingival thickness [GT] change, and recession depth [RD] reduction). Results A total of 48 trials reported in 55 articles were selected. All studies reported on the treatment of gingival recession defects for root coverage purposes. Forty‐six treatment arms from 24 trials were included in the NMA. These arms consisted of treatment with coronally advanced flap (CAF) alone, EMD + CAF, platelet‐rich fibrin (PRF) + CAF, and subepithelial connective tissue graft (SCTG) + CAF. Regarding MRC%, SCTG+CAF was associated with a significant higher estimate (13.41%, 95% CI [8.06‒18.75], P < 0.01), while EMD+CAF (6.68%, 95% CI [−0.03 to 13.4], P = 0.061) and PRF+CAF (1.03%, 95% CI [−5.65 to 7.72], P = 0.71) failed to show statistically significant differences compared with CAF alone (control group) or with each other. Similarly, only SCTG+CAF led to a significantly higher CRC% (14.41%, 95% CI [4.21 to 24.61], P < 0.01), while treatment arms EMD + CAF (13.48%, 95% CI [−3.34 to 30.32], P = 0.11) and PRF+CAF (–0.91%, 95% CI [−15.38, 13.57], p = 0.81) did not show significant differences compared with CAF alone or with each other. Differences in the CI of PRF+CAF (symmetrical around a zero adjunctive effect) and EMD+CAF (non‐symmetrical) suggest that EMD could have some additional value compared with PRF. Treatment with SCTG+CAF led to a statistically significant higher RD reduction (–0.39 mm, 95% CI [−0.55 to 0.22], P < 0.01), however EMD+CAF (–0.13 mm, 95% CI [−0.29 to 0.01], P = 0.08) and PRF+CAF (–0.06 mm, 95% CI [−0.23 to 0.09], P = 0.39) failed to show significant differences compared with CAF or with each other. While SCTG+CAF was associated with a statistically significant higher gain of KTW (0.71 mm, 95% CI [0.48 to 0.93], P < 0.01), EMD+CAF (0.24 mm, 95% CI [−0.02 to 0.51], P = 0.08) and PRF+CAF (0.08 mm, 95% CI [−0.23 to 0.41], P = 0.58) did not result into significant changes compared with CAF alone or with each other. Regarding the use of rhPDGF–BB+CAF, although available studies have reported equivalent results compared with SCTG+CAF, evidence is very limited. Conclusions The use of ABPs, EMD, or rhPDGF‐BB in conjunction with a CAF for root coverage purposes is safe and generally promotes significant improvements respective to baseline clinical parameters. However, the adjunctive use of ABPs and EMD does not provide substantial additional improvements in terms of clinical outcomes and patient‐reported outcome measures to those achieved using CAF alone, when baseline KTW is >2 mm. Both PRF+CAF and EMD+CAF rendered inferior MRC%, CRC%, RD reduction, and KTW gain compared with SCTG+CAF, which should still be considered the gold‐standard in root coverage therapy. Although some studies have reported equivalent results for rhPDGF‐BB+CAF compared with the gold‐standard intervention, limited evidence precludes formal comparisons with CAF or SCTG+CAF that could be extrapolated to guide clinical practice.