Journal of Southern Medical University

Journal of Southern Medical University ›› 2024, Vol. 44 ›› Issue (3): 533-540.doi: 10.12122/j.issn.1673-4254.2024.03.15

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A sericin hydrogel scaffold for sustained dexamethasone release modulates macrophage polarization to promote mandibular bone defect repair in rats

FAN Yiping, LUO Menglin, HUANG Dongzong, LIU Lin, FU Bo, WANG Xiaoyu, GUAN Miaosheng, LI Hongbo   

  1. Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing 100853, China; Department of Stomatology, Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China; Department of Stomatology, The Strategic Support Force Medical Center of PLA, Beijing 100101, China; Department of Research, PLARocket Force Characteristic Medical Center, Beijing 100088, China
  • Online:2024-03-20 Published:2024-04-03

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Abstract: Objective To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone (SMH-CD/DEX) scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization. Methods The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin (NH2-β-CD) and sericin hydrogel and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), biocompatibility assessment and drug release test. THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1, mRNA expressions of IL-6, Il-10, Arg-1 and iNOS, and surface markers CD86 and CD206 using Western blotting, RT-qPCR, and flow cytometry. In a co-culture system of human periodontal ligament stem cells (HPDLSCs) and THP-1 macrophages, the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP, Runx2, OCN and BMP2 mRNA, ALP staining, and alizarin red staining. In a rat model of mandibular bone defect, the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining. Results In THP-1 macrophages, incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions. In the co-culture system, SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation. In the rat models, implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect. Conclusion The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Key words: macrophage; human periodontal ligament stem cells; immunoregulation; bone regeneration; drug delivery