Recombinant factors for periodontal intrabony defects: A systematic review and network meta‐analysis of preclinical studies

The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human‐derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta‐analysis of pre‐clinical studies. The systematic review and network meta‐analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre‐clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm2), bone volume density (g/cm3) and bone height (mm) data was extracted. The analysis was carried out using network meta‐analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP‐2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF‐5/TCP ranked best in the bone area (mm2), rhPDGF‐BB/Equine ranked best in bone height (mm), rhBMP‐2 ranked best in the percentage of new bone fill, rhBMP‐2/ACS ranked best in new cementum formation, and rhGDF‐5/b‐ TCP/PLGA ranked best in connective tissue attachment and junctio