ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1632000
Zirconia/Dental Pulp Stem Cell Composite Scaffolds Repair Osteogenic Defect via Regulating Macrophages
Provisionally accepted
- Department of Stomatology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Background: Dental pulp stem cells (DPSCs) possess multilineage differentiation potential and immunomodulatory properties, making them promising candidates for bone regeneration. In this study, the regenerative potential of DPSCs combined with nitrogen-doped reduced graphene oxide/zirconia (N-Rgo/ZrO2) composite scaffolds was investigated in vitro and in a rat jaw injury model. Methods: The primary human DPSCs were characterized by flow cytometry (CD90/CD29/CD45) and trilineage differentiation assays. In vitro effects on macrophage polarization (IL-6, TNF-α, CD206, Arg1, iNOS, IL-10) and MAPK signaling (p-ERK1/2, p-p38) were analyzed using qRT-PCR and Western blot. A rat bone defect model was established to evaluate mandibular bone regeneration through H&E staining, Masson’s trichrome, and molecular analysis of osteogenic markers (RUNX2, ALP, Osterix, OPN, OCN) and pathway activation. Results: DPSCs exhibited characteristic mesenchymal markers (CD90⁺: 90.16±1.00%; CD29⁺: 99.27±0.11%) and multilineage differentiation capacity. N-Rgo/ZrO2+DPSCs synergistically upregulated M2 macrophage markers (CD206, Arg1, IL-10) and pro-osteogenic cytokines (TNF-α) while suppressing IL-6. This combination potently activated p-ERK1/2 and p-p38 MAPK, exceeding single-treatment effects. In vivo, cotreatment restored trabecular architecture (collagen fiber density), improved rat pathological conditions, and significantly elevated osteogenic markers (RUNX2, ALP, Osterix, OPN and OCN) compared with monotherapies. Conclusion: The N-Rgo/ZrO2+DPSCs composite promotes bone regeneration through dual mechanisms: (1) immunomodulation through M2 macrophage polarization and MAPK pathway activation and (2) direct osteogenic differentiation. This strategy demonstrates superior efficacy to individual components, offering a novel combinatorial approach for maxillofacial bone repair.
Keywords: dental pulp stem cells, Bone Regeneration, Macrophage polarization, MAPK signaling, Zirconia
Received: 20 May 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Wu, He, Li, Shang, Hu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bingyao Liu, Department of Stomatology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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