Non-Cochrane · intervention · PM42243748
Clinical efficacy of different biomaterials for the regenerative treatment of periodontal intrabony defects: a systematic review and Bayesian network meta-analysis.
Zhou Yikun, Zhang Gengming, Wang Mei, et al. · BMC oral health · 2026 · PubMed · doi:10.1186/s12903-026-08671-2
Findings
Population Adults with periodontitis and periodontal intrabony defects
11 findings
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Open flap debridement (OFD) | Probing depth (PD) reduction 6-48 months · Periodontal regenerative surgery | MD 1.8 [0.27, 3.31] GRADE not reported Studies not reported |
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Open flap debridement (OFD) | Radiographic bone gain (mm) 6-48 months · Periodontal regenerative surgery | MD 2.51 [0.22, 4.81] GRADE not reported Studies not reported |
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Open flap debridement (OFD) | Clinical attachment level (CAL) gain 6-48 months · Periodontal regenerative surgery | MD 1.88 [0.32, 3.45] 1.88 [0.32, 3.45] mm Moderate Downgraded: inconsistency 31 studies · 1875 participants |
| Bone graft combined with PRF (BoneGraft_PRF) | Open flap debridement (OFD) | Probing depth (PD) reduction 6-48 months · Periodontal regenerative surgery | MD 2.09 [0.45, 3.75] 2.09 [0.45, 3.75] mm Moderate Downgraded: inconsistency 29 studies · 1482 participants |
| Bone graft combined with PRF (BoneGraft_PRF) | Open flap debridement (OFD) | Clinical attachment level (CAL) gain 6-48 months · Periodontal regenerative surgery | MD 2.64 [1.09, 4.2] GRADE not reported Studies not reported |
| Bone graft combined with PRF (BoneGraft_PRF) | Open flap debridement (OFD) | Radiographic bone gain (mm) 6-48 months · Periodontal regenerative surgery | MD 2.76 [0.94, 4.59] 2.76 [0.94, 4.59] mm Moderate Downgraded: inconsistency 23 studies · 1324 participants |
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Bone graft combined with PRF (BoneGraft_PRF) | Clinical attachment level (CAL) gain 6-48 months · Periodontal regenerative surgery | MD -0.76 [-2.83, 1.29] GRADE not reported Studies not reported |
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Bone graft combined with PRF (BoneGraft_PRF) | Radiographic bone gain (mm) 6-48 months · Periodontal regenerative surgery | MD -0.25 [-2.88, 2.36] GRADE not reported Studies not reported |
| FGF-2 combined with bone graft (FGF2_BoneGraft) | Bone graft combined with PRF (BoneGraft_PRF) | Probing depth (PD) reduction 6-48 months · Periodontal regenerative surgery | MD -0.29 [-2.44, 1.85] GRADE not reported Studies not reported |
| PRF combined with ascorbic acid (PRF_AA) | Open flap debridement (OFD) | Gingival recession (REC; lower is better) 6-24 months · Periodontal regenerative surgery | MD -2.57 [-6.62, 1.47] -2.57 [-6.62, 1.47] mm Low Downgraded: imprecision, inconsistency 11 studies · 558 participants |
| PRF combined with ascorbic acid (PRF_AA) | Platelet-rich fibrin (PRF) | Gingival recession (REC; lower is better) 6-24 months · Periodontal regenerative surgery | MD -0.59 [-3.99, 2.87] GRADE not reported Studies not reported |
Included primary studies 63
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ferrarotti 2018 Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial. PMID:29779220 | 2018 | 4 other reviews | not stated | not extracted yet |
| Martande 2012 Platelet-Rich Fibrin Combined With 1.2% Atorvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled… PMID:27294433 | 2016 | 3 other reviews | not stated | not extracted yet |
| Liu 2021 Treatment of periodontal intrabony defects using bovine porous bone mineral and guided tissue regeneration with/without platelet-rich… PMID:33569807 | 2021 | 2 other reviews | not stated | not extracted yet |
| Mazzonetto 2021 Clinical, radiographic, and patient‐centered outcomes after use of enamel matrix proteins for the treatment of intrabony defects in… DOI:10.1002/jper.20-0493 | 2020 | 2 other reviews | not stated | not extracted yet |
| Mubarak 2023 Adjunctive effect of collagen membrane coverage to L-PRF in the treatment of periodontal intrabony defects: a randomized controlled… PMID:37667213 | 2023 | 2 other reviews | not stated | not extracted yet |
| Pradeep 2016 Synergistic Approach Using Platelet-Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized… PMID:27562221 | 2016 | 2 other reviews | not stated | not extracted yet |
| Abd El-Azeem 2023 The use of integrin binding domain loaded hydrogel (RGD) with minimally invasive surgical technique in treatment of periodontal intrabony… PMID:38126565 | 2023 | 1 other review | not stated | not extracted yet |
| Bajaj 2017 Autologous Platelet‐Rich Fibrin in the Treatment of 3‐Wall Intrabony Defects in Aggressive Periodontitis: A Randomized Controlled Clinical… DOI:10.1902/jop.2017.120661 | 2017 | 1 other review | not stated | not extracted yet |
| Bajaj 2017 Autologous Platelet-Rich Fibrin in the Treatment of 3-Wall Intrabony Defects in Aggressive Periodontitis: A Randomized Controlled Clinical… PMID:28820320 | 2017 | 1 other review | not stated | not extracted yet |
| Chatterjee 2016 Treatment of periodontal intrabony defects using autologous platelet‐rich fibrin and titanium platelet‐rich fibrin: a randomized,… DOI:10.1111/jicd.12231 | 2016 | 1 other review | not stated | not extracted yet |
| Chatterjee 2016 Treatment of periodontal intrabony defects using autologous platelet-rich fibrin and titanium platelet-rich fibrin: a randomized,… PMID:27477110 | 2017 | 1 other review | not stated | not extracted yet |
| Ferrarotti 2018 Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial DOI:10.1111/jcpe.12931 | 2018 | 1 other review | not stated | not extracted yet |
| Gorski 2018 Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: a 12-month randomized controlled trial. PMID:29411112 | 2018 | 1 other review | not stated | not extracted yet |
| Liu 2021 Treatment of periodontal intrabony defects using bovine porous bone mineral and guided tissue regeneration with/without platelet‐rich… DOI:10.1002/jper.20-0860 | 2021 | 1 other review | not stated | not extracted yet |
| Martande 2012 Platelet‐Rich Fibrin Combined With 1.2% Atorvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled… DOI:10.1902/jop.2016.150306 | 2016 | 1 other review | not stated | not extracted yet |
| Mazzonetto 2021 Clinical, radiographic, and patient-centered outcomes after use of enamel matrix proteins for the treatment of intrabony defects in… PMID:33107596 | 2021 | 1 other review | not stated | not extracted yet |
| Mubarak 2023 Adjunctive effect of collagen membrane coverage to L-PRF in the treatment of periodontal intrabony defects: a randomized controlled… DOI:10.1186/s12903-023-03332-0 | 2023 | 1 other review | not stated | not extracted yet |
| Ozkal Eminoglu 2024 The effect of titanium-platelet rich fibrin on periodontal intrabony defects: A randomized controlled split-mouth clinical study. PMID:38843242 | 2024 | 1 other review | not stated | not extracted yet |
| Paolantonio 2010 Autogenous Periosteal Barrier Membranes and Bone Grafts in the Treatment of Periodontal Intrabony Defects of Single‐Rooted Teeth: A… DOI:10.1902/jop.2010.100094 | 2010 | 1 other review | not stated | not extracted yet |
| Pradeep 2012 Comparative Evaluation of Autologous Platelet‐Rich Fibrin and Platelet‐Rich Plasma in the Treatment of 3‐Wall Intrabony Defects in Chronic… DOI:10.1902/jop.2012.110705 | 2012 | 1 other review | not stated | not extracted yet |
| Pradeep 2012 Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of 3-wall intrabony defects in chronic… PMID:22348695 | 2012 | 1 other review | not stated | not extracted yet |
| Pradeep 2016 Synergistic Approach Using Platelet‐Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized… DOI:10.1902/jop.2016.150698 | 2016 | 1 other review | not stated | not extracted yet |
| Rodriguez 2025 Comparision of crosslinked hyaluronic acid vs. enamel matrix derivative for periodontal regeneration: an 18-month follow-up randomized… PMID:40106008 | 2025 | 1 other review | not stated | not extracted yet |
| Samarth 2022 Comparative evaluation of demineralized freeze-dried bone allograft with and without concentrated growth factor membrane in the treatment… DOI:10.1007/s00784-022-04791-5 | 2022 | 1 other review | not stated | not extracted yet |
| Santana 2015 Human intrabony defect regeneration with rh <scp>FGF</scp> ‐2 and hyaluronic acid – a randomized controlled clinical trial DOI:10.1111/jcpe.12406 | 2015 | 1 other review | not stated | not extracted yet |
| Sreeparvathy 2024 Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A… DOI:10.1590/1678-7757-2023-0442 | 2024 | 1 other review | not stated | not extracted yet |
| Sreeparvathy 2024 Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A… PMID:39109750 | 2024 | 1 other review | not stated | not extracted yet |
| Thorat 2017 Adjunctive Effect of Autologous Platelet-Rich Fibrin in the Treatment of Intrabony Defects in Localized Aggressive Periodontitis Patients:… DOI:10.11607/prd.2972 | 2017 | 1 other review | not stated | not extracted yet |
| Thorat 2017 Adjunctive Effect of Autologous Platelet-Rich Fibrin in the Treatment of Intrabony Defects in Localized Aggressive Periodontitis Patients:… PMID:29023611 | 2017 | 1 other review | not stated | not extracted yet |
| Abd El-Azeem 2023 The use of integrin binding domain loaded hydrogel (RGD) with minimally invasive surgical technique in treatment of periodontal intrabony… DOI:10.1590/1678-7757-2023-0263 | 2023 | this review only | not stated | not extracted yet |
| Abdulrahman 2022 Clinical and radiographic evaluation of low-speed platelet-rich fibrin (PRF) for the treatment of intra-osseous defects of stage-III… DOI:10.1007/s00784-022-04627-2 | 2022 | this review only | not stated | not extracted yet |
| Abdulrahman 2022 Clinical and radiographic evaluation of low-speed platelet-rich fibrin (PRF) for the treatment of intra-osseous defects of stage-III… PMID:35876893 | 2022 | this review only | not stated | not extracted yet |
| Agarwal 2015 Platelet rich fibrin combined with decalcified freeze-dried bone allograft for the treatment of human intrabony periodontal defects: a… DOI:10.3109/00016357.2015.1035672 | 2015 | this review only | not stated | not extracted yet |
| Agarwal 2015 Platelet rich fibrin combined with decalcified freeze-dried bone allograft for the treatment of human intrabony periodontal defects: a… PMID:25972081 | 2016 | this review only | not stated | not extracted yet |
| Alshujaa 2024 Clinical and radiographic evaluation of the use of PRF, CGF, and autogenous bone in the treatment of periodontal intrabony defects:… DOI:10.1002/jper.23-0481 | 2023 | this review only | not stated | not extracted yet |
| Alshujaa 2024 Clinical and radiographic evaluation of the use of PRF, CGF, and autogenous bone in the treatment of periodontal intrabony defects:… PMID:37986648 | 2024 | this review only | not stated | not extracted yet |
| Elbehwashy 2021 Clinical and radiographic effects of ascorbic acid-augmented platelet-rich fibrin versus platelet-rich fibrin alone in intra-osseous… DOI:10.1007/s00784-021-03929-1 | 2021 | this review only | not stated | not extracted yet |
| Elbehwashy 2021 Clinical and radiographic effects of ascorbic acid-augmented platelet-rich fibrin versus platelet-rich fibrin alone in intra-osseous… PMID:33842996 | 2021 | this review only | not stated | not extracted yet |
| Galav 2016 Comparative evaluation of platelet-rich fibrin and autogenous bone graft for the treatment of infrabony defects in chronic periodontitis:… DOI:10.4103/0970-9290.195634 | 2016 | this review only | not stated | not extracted yet |
| Galav 2016 Comparative evaluation of platelet-rich fibrin and autogenous bone graft for the treatment of infrabony defects in chronic periodontitis:… PMID:27966508 | 2016 | this review only | not stated | not extracted yet |
| Górski 2018 Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: a 12-month randomized controlled trial DOI:10.1007/s00784-018-2368-3 | 2018 | this review only | not stated | not extracted yet |
| Heinz 2010 Clinical effects of nanocrystalline hydroxyapatite paste in the treatment of intrabony periodontal defects: a randomized controlled… DOI:10.1007/s00784-009-0325-x | 2009 | this review only | not stated | not extracted yet |
| Heinz 2010 Clinical effects of nanocrystalline hydroxyapatite paste in the treatment of intrabony periodontal defects: a randomized controlled… PMID:19680697 | 2010 | this review only | not stated | not extracted yet |
| Imamura 2024 Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 in combination with carbonate apatite granules… DOI:10.1007/s00784-024-05979-7 | 2024 | this review only | not stated | not extracted yet |
| Imamura 2024 Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 in combination with carbonate apatite granules… PMID:39373727 | 2024 | this review only | not stated | not extracted yet |
| Kishore 2013 Evaluation of Relative Efficacy of β-Tricalcium Phosphate with and without Type I Resorbable Collagen Membrane in Periodontal Infrabony… DOI:10.5005/jp-journals-10024-1299 | 2013 | this review only | not stated | not extracted yet |
| Kishore 2013 Evaluation of relative efficacy of β-tricalcium phosphate with and without type I resorbable collagen membrane in periodontal infrabony… PMID:23811645 | 2013 | this review only | not stated | not extracted yet |
| Kitamura 2016 Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth… DOI:10.1002/jbmr.2738 | 2015 | this review only | not stated | not extracted yet |
| Kitamura 2016 Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth… PMID:26547659 | 2016 | this review only | not stated | not extracted yet |
| Kojima 2024 Recombinant human fibroblast growth factor and autogenous bone for periodontal regeneration: Alone or in combination? A randomized… DOI:10.1111/jre.13310 | 2024 | this review only | not stated | not extracted yet |
| Kojima 2024 Recombinant human fibroblast growth factor and autogenous bone for periodontal regeneration: Alone or in combination? A randomized… PMID:38853125 | 2024 | this review only | not stated | not extracted yet |
| Lee & Jeong 2021 Long-term stability of adjunctive use of enamel matrix protein derivative on porcine-derived xenograft for the treatment of one-wall… PMID:34050681 | 2022 | this review only | not stated | not extracted yet |
| Lee 2021 Long‐term stability of adjunctive use of enamel matrix protein derivative on porcine‐derived xenograft for the treatment of one‐wall… DOI:10.1002/jper.21-0254 | 2021 | this review only | not stated | not extracted yet |
| Ozkal Eminoglu 2024 The effect of titanium-platelet rich fibrin on periodontal intrabony defects: A randomized controlled split-mouth clinical study DOI:10.1371/journal.pone.0304970 | 2024 | this review only | not stated | not extracted yet |
| Paolantonio 2010 Autogenous periosteal barrier membranes and bone grafts in the treatment of periodontal intrabony defects of single-rooted teeth: a… PMID:20583915 | 2010 | this review only | not stated | not extracted yet |
| Rodríguez 2025 Comparision of crosslinked hyaluronic acid vs. enamel matrix derivative for periodontal regeneration: an 18-month follow-up randomized… DOI:10.1007/s00784-025-06278-5 | 2025 | this review only | not stated | not extracted yet |
| Samarth 2022 Comparative evaluation of demineralized freeze-dried bone allograft with and without concentrated growth factor membrane in the treatment… PMID:36441270 | 2023 | this review only | not stated | not extracted yet |
| Santana 2015 Human intrabony defect regeneration with rhFGF-2 and hyaluronic acid - a randomized controlled clinical trial. PMID:25933201 | 2015 | this review only | not stated | not extracted yet |
| Sener 2025 Effect of 0.8% Hyaluronic Acid-Based Gel on Clinical and Biomolecular parameters in the surgical periodontal treatment of Stage III… PMID:40643719 | 2025 | this review only | not stated | not extracted yet |
| Şener 2025 Effect of 0.8% Hyaluronic Acid-Based Gel on Clinical and Biomolecular parameters in the surgical periodontal treatment of Stage III… DOI:10.1007/s00784-025-06449-4 | 2025 | this review only | not stated | not extracted yet |
| Seshima 2022 Periodontal Regenerative Therapy Using rhFGF-2 and Deproteinized Bovine Bone Mineral versus rhFGF-2 Alone: 4-Year Extended Follow-Up of a… PMID:36421696 | 2022 | this review only | not stated | not extracted yet |
| Temraz 2019 Clinical and radiographic evaluation of amnion chorion membrane and demineralized bone matrix putty allograft for management of… DOI:10.1007/s10561-018-09743-6 | 2019 | this review only | not stated | not extracted yet |
| Temraz 2019 Clinical and radiographic evaluation of amnion chorion membrane and demineralized bone matrix putty allograft for management of… PMID:30631986 | 2019 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults aged 18 or more with periodontitis and periodontal intrabony defects | Patients with periodontal intrabony defects (n=703 patients in 32 RCTs) |
| Intervention | Biomaterial-based regenerative therapies: bone grafts, platelet concentrates, EMD, FGF-2, barrier membranes, stem cells and combinations | 14 treatment nodes: OFD, BoneGraft, PRF, PRP, EMD, FGF2, FGF2_BoneGraft, BoneGraft_PRF, StemCells, BarrierMembrane, BoneGraft_BarrierMembrane, DrugAdjunct, RGD, PRF_AA |
| Comparison | OFD or other regenerative biomaterial strategies | OFD and other regenerative strategies (network) |
| Outcomes | Change from baseline in PD, CAL, bone gain (mm), gingival recession | CAL gain (31 studies), PD reduction (29), bone gain (23), REC (11) |
| Study designs | RCTs (parallel-group or split-mouth) | 32 RCTs |
| Timing | Not specified | Follow-up 6 to 48 months |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | Yes | No | no |
| 4Comprehensive literature searchcritical | No | No | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | No | Yes | no |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | NRSI: N/A · RCT: Yes | RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | NRSI: N/A · RCT: No | RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |