Work

Zirconia/dental pulp stem cell composite scaffolds repair osteogenic defect via regulating macrophages

Year: 2025

Type: article

Abstract: 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.

Source: Frontiers in Bioengineering and Biotechnology

DOI: 10.3389/fbioe.2025.1632000

Authors: Yingying Wu, Maodian He, Cuimei Li, Weihua Shang, Jiale Hu, Bingyao Liu

Institution: Nanjing University

Language: English

Topic: Bone Tissue Engineering Materials

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801