Journal of Molecular Pathology · Published 2026-06-15 · DOI 10.3390/jmp7020024
Gulnihol Sharipova, Jasur Rizaev, Shuxrat Boymuradov, Mirzaakbar Kamolov, Adolat Mamadiyorova, Latipov Javdat, Umarov Doniyor, Nozimjon Ibrokhimov
<b>Background/Objectives</b>: Endodontic perforation repair requires biomaterials that balance sealing ability with minimal cellular injury. AH Plus (epoxy resin-based) remains widely used despite cytotoxicity concerns. CeraSeal (calcium silicate-based bioceramic) is a potentially more biocompatible alternative. However, comparative data on sealer-induced cytotoxicity and inflammatory responses remain limited. This study compared the cytotoxicity and inflammatory profiles of CeraSeal and AH Plus using in vitro and in vivo approaches. <b>Methods</b>: Human periodontal ligament stem cells (hPDLSCs) were exposed to sealer extracts (1:4 AH Plus, 1:8 CeraSeal) for 120 h. Cell death was assessed by MTT, Live/Dead, LDH release, and Annexin V/PI flow cytometry. Oxidative stress was quantified via ROS generation (DCFH-DA). In a rat furcation perforation model (<i>n</i> = 8 teeth/group), inflammatory markers (TNF-α, IL-1β, CD68), osteogenic activity (ALP), and osteoclasts (TRAP) were evaluated. <b>Results</b>: AH Plus was associated with significantly greater necrotic cell death (357.6 ± 47.6% LDH release vs. CeraSeal 128.8 ± 37.5%; <i>p</i> = 0.0079) and reduced hPDLSC viability at all time points (<i>p</i> < 0.0001). ROS generation was comparable between sealers (~32–35%, <i>p</i> > 0.05). In vivo, IL-1β was higher in AH Plus-treated tissues (52.25 vs. 24.88 cells/mm<sup>2</sup>; <i>p</i> = 0.0002), while TNF-α and CD68 were greater in CeraSeal (<i>p</i> ≤ 0.0011). ALP was higher in AH Plus (median 6.15 vs. 3.68; <i>p</i> = 0.0002), with no difference in TRAP-positive osteoclasts. Morphometric analysis showed superior cellular preservation with CeraSeal (<i>p</i> = 0.0079), while inflammatory infiltration was higher in CeraSeal (<i>p</i> = 0.0002). <b>Conclusions</b>: AH Plus was associated with a necrotic-inflammatory profile with elevated IL-1β and higher ALP expression. CeraSeal demonstrated better cellular preservation, lower LDH release, and a distinct inflammatory signature (higher TNF-α and CD68). These findings establish comparative response profiles for the two sealers and support CeraSeal as a potentially biocompatible alternative, though further mechanistic studies are warranted.
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Sharipova, G., Rizaev, J., Boymuradov, S., et al. (2026). Comparative Cytotoxicity and Inflammatory Profiles of CeraSeal Versus AH Plus in Periodontal Tissue Repair: An In Vitro and In Vivo Study. Journal of Molecular Pathology. https://doi.org/10.3390/jmp7020024