Análises de fatores que influenciam o procedimento endodôntico regenerativo: análise bibliométrica e avaliação laboratorial

Abstract

This study evaluated factors that may influence regenerative endodontic procedure (REP) through: (1) Bibliometric analysis of the 100 most-cited articles in regenerative endodontics; (2) the synthesis and analysis of a novel thermosensitive chitosan-based hydrogel containing azithromycin (AZI) for REP; and (3) an assessment of the influence of diabetes mellitus (DM) on the regenerative process following REP with or without injectable platelet-rich fibrin (iPRF) in immature rat molars. For the bibliometric study, articles categorized under 'Dentistry, Oral Surgery & Medicine' were retrieved from the Web of Science database (2019-23); bibliometric data were extracted, analyzed, and visualized using VOSviewer software. For the laboratory study, a chitosan-based hydrogel combined with a gelling agent and loaded with varying concentrations of AZI was produced; morphological, rheological, mechanical, and biological properties were assessed. In the third study, 24 rats were divided into normoglycemic and DM-induced groups, then further allocated into four groups (n = 6): REP, REP-DM, REP-iPRF, and REP-iPRF-DM. After induction of pulp necrosis, molars underwent disinfection and intracanal bleeding induction; iPRF (1200 rpm, 8 min) was applied in the REP-iPRF and REP-iPRF-DM groups. At 21 days, animals were euthanized and samples prepared for histological, immunohistochemical, and statistical analyses (p < 0.05). Results indicated that the most cited articles had up to 85 citations, were predominantly laboratory-based (n = 47), mainly published in 2020 (48%) in the Journal of Endodontics (47%), with primary authorship from the United States (USA). A. Azim was the most cited author, and the University of Hong Kong was the most productive institution. Keywords such as “regenerative endodontics” and “stem cells” were frequently observed. In the laboratory study, the incorporation of AZI did not compromise the hydrogel’s thermosensitivity, injectability, or mechanical strength but reduced cell viability. Hydrogels with 3% and 5% AZI minimized cytotoxic effects and enhanced antibacterial activity. The 3% AZI hydrogel improved mineralization and vasculogenesis compared to the necrosis group and a double antibiotic paste group (50 mg/mL), respectively (p < 0.05). In the last study, the REP-DM group exhibited significantly reduced formation of connective and mineralized tissues compared to the REP group (p < 0.05), as well as lower collagen maturation in the REP-DM group (p < 0.05). Collagen was predominantly immature; however, REP-DM-iPRF showed greater mature collagen fibers than REP-DM (p < 0.05). REP-DM showed lower immunolabeling of TGF-β1 and OCN compared to REP and REP-iPRF-DM groups, respectively (p < 0.05). In conclusion: (1) The 100 most cited articles were predominantly laboratory-based studies from the USA, focusing on biomaterials, scaffold design, and stem cells; (2) the injectable 3% AZI hydrogel reduced inflammation, improved disinfection, and enhanced mineralization and vasculogenesis; (3) DM impaired connective and mineralized tissue formation in immature necrotic rat molars and decreased TGF-β1 and OCN immunolabeling. However, the use of iPRF enhanced TGF-β1 and OCN immunolabelling in diabetic animals, in addition to greater collagen maturation.