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Background <p>Furcation involvement, a severe complication of chronic periodontitis, poses significant challenges for clinical regeneration because of failure to remodel the inflammatory microenvironment. Current strategies such as guided tissue regeneration are limited by two-dimensional architecture and insufficient immunomodulation, resulting in failure to restore functional periodontal tissues. Cell pellet, a novel scaffold-free technology, features self-assembled three-dimensional structures and endogenous extracellular matrix storing growth factors; however, its immunomodulatory mechanism, particularly with respect to macrophage polarization, remains uncharacterized.</p> Objective <p>To investigate the effects of cell pellets on macrophage polarization and its molecular mechanisms and to validate their in vivo efficacy in promoting periodontal bone regeneration by reshaping the inflammatory microenvironment in FI.</p> Methods <p>In this study, a coculture system involving cell pellet and Raw 264.7 cells was established to elucidate the impact of the cell pellet on macrophage polarization. rTGF-β1 and an inhibitor of the TGFβI/II receptor (LY2109761) were used to investigate the underlying mechanisms of macrophage polarization. Finally, in vivo studies were conducted by implanting the cell pellet into a rat tooth root fenestration defect model to assess its regenerative potential and immunomodulatory effects.</p> Results <p>When cocultured with macrophages, the cell pellet was observed to polarize the macrophages toward the M2 phenotype. This effect could be counteracted by the use of a TGF-β receptor inhibitor. In vivo studies have shown that the cell pellet effectively transitions proinflammatory M1 macrophages into a pro-healing M2 phenotype, restores the M2/M1 ratio to a physiological balance, efficiently resolves inflammatory responses, and ultimately augments osteoblastic differentiation and promotes bone regeneration.</p> Conclusion <p>Cell pellets promote periodontal regeneration by orchestrating M2 macrophage polarization via paracrine TGF-β1, suggesting a scaffold-free strategy that integrates immunomodulation and structural support for FI treatment.</p> Clinical significance <p>This study provides a novel scaffold-free therapeutic option for furcation involvement, addressing the clinical bottleneck of insufficient immunomodulation and limited regenerative efficacy of traditional treatments. The TGF-β1-mediated immunomodulatory and regenerative effects of cell pellets offer a promising approach to improve functional periodontal tissue restoration and tooth preservation in clinical practice.</p>

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Cell pellets promote periodontal bone regeneration in furcation involvement by regulating macrophage polarization through TGF-β1 secretion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Fangfang Xu,
  • Le Bai,
  • Xiang Liang,
  • Sina Ahmadi,
  • Xin Yang,
  • Huan Liu,
  • Xinyi Li,
  • Xinyi Hou,
  • Junbo Tu,
  • Xinpeng Dai,
  • Sijia Na

摘要

Background

Furcation involvement, a severe complication of chronic periodontitis, poses significant challenges for clinical regeneration because of failure to remodel the inflammatory microenvironment. Current strategies such as guided tissue regeneration are limited by two-dimensional architecture and insufficient immunomodulation, resulting in failure to restore functional periodontal tissues. Cell pellet, a novel scaffold-free technology, features self-assembled three-dimensional structures and endogenous extracellular matrix storing growth factors; however, its immunomodulatory mechanism, particularly with respect to macrophage polarization, remains uncharacterized.

Objective

To investigate the effects of cell pellets on macrophage polarization and its molecular mechanisms and to validate their in vivo efficacy in promoting periodontal bone regeneration by reshaping the inflammatory microenvironment in FI.

Methods

In this study, a coculture system involving cell pellet and Raw 264.7 cells was established to elucidate the impact of the cell pellet on macrophage polarization. rTGF-β1 and an inhibitor of the TGFβI/II receptor (LY2109761) were used to investigate the underlying mechanisms of macrophage polarization. Finally, in vivo studies were conducted by implanting the cell pellet into a rat tooth root fenestration defect model to assess its regenerative potential and immunomodulatory effects.

Results

When cocultured with macrophages, the cell pellet was observed to polarize the macrophages toward the M2 phenotype. This effect could be counteracted by the use of a TGF-β receptor inhibitor. In vivo studies have shown that the cell pellet effectively transitions proinflammatory M1 macrophages into a pro-healing M2 phenotype, restores the M2/M1 ratio to a physiological balance, efficiently resolves inflammatory responses, and ultimately augments osteoblastic differentiation and promotes bone regeneration.

Conclusion

Cell pellets promote periodontal regeneration by orchestrating M2 macrophage polarization via paracrine TGF-β1, suggesting a scaffold-free strategy that integrates immunomodulation and structural support for FI treatment.

Clinical significance

This study provides a novel scaffold-free therapeutic option for furcation involvement, addressing the clinical bottleneck of insufficient immunomodulation and limited regenerative efficacy of traditional treatments. The TGF-β1-mediated immunomodulatory and regenerative effects of cell pellets offer a promising approach to improve functional periodontal tissue restoration and tooth preservation in clinical practice.