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Background <p>Delayed healing of post-operative anal fistula wounds is driven by a hostile inflammatory microenvironment. While autologous concentrated growth factors (ACGF) show regenerative potential, the underlying immunomolecular mechanisms remain unclear. This study investigates if ACGF accelerates contaminated wound healing by modulating macrophage polarization via the AKT/mTOR pathway.</p> Methods <p>In vitro, RAW264.7 macrophages were treated with ACGF to assess phenotypic switching and AKT/mTOR activation. The paracrine effects of ACGF-primed macrophages on fibroblasts were evaluated using a co-culture system with AKT-siRNA validation. In vivo, a rat fecal-contaminated wound model was established. Therapeutic efficacy, with or without the AKT inhibitor Triciribine, was assessed via laser speckle imaging, histology, and immunofluorescence.</p> Results <p>ACGF effectively reprogrammed macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, significantly upregulating CD206 and Arg-1 expression while activating AKT/mTOR signaling. Mechanistically, ACGF-primed macrophages significantly boosted RSF proliferation, migration, and collagen synthesis, effects that were substantially abrogated by AKT silencing. In vivo, ACGF treatment markedly accelerated wound closure, enhanced microvascular perfusion, and increased the density of CD31 + and Ki67 + cells. These regenerative benefits were accompanied by a significant shift toward M2 infiltration and a reduction in pro-inflammatory cytokines, all of which were reversed by pharmacological inhibition of AKT.</p> Conclusion <p>ACGF promotes the healing of contaminated wounds by orchestrating an AKT/mTOR-dependent macrophage M2 polarization. This shift initiates a beneficial paracrine relay that enhances fibroblast activity and neoangiogenesis, effectively restoring the regenerative niche. Our findings establish ACGF as a potent immunomodulatory biomaterial and offer a promising therapeutic strategy for complex perianal wounds and chronic recalcitrant defects.</p>

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Autologous concentrated growth factors promote M2 macrophage polarization to accelerate wound healing after anal fistula surgery by activating the AKT/mTOR pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

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  • Xiufeng Zhang,
  • Mengjie Zhong,
  • Feifei Zhang,
  • Miaoshan Lim,
  • Jiazi Yu,
  • Rongchao He,
  • Jianming Qiu,
  • Yuemin Yuan,
  • Zhenfeng Lu,
  • Houdong Wang,
  • Zhong Shen,
  • Jun He

摘要

Background

Delayed healing of post-operative anal fistula wounds is driven by a hostile inflammatory microenvironment. While autologous concentrated growth factors (ACGF) show regenerative potential, the underlying immunomolecular mechanisms remain unclear. This study investigates if ACGF accelerates contaminated wound healing by modulating macrophage polarization via the AKT/mTOR pathway.

Methods

In vitro, RAW264.7 macrophages were treated with ACGF to assess phenotypic switching and AKT/mTOR activation. The paracrine effects of ACGF-primed macrophages on fibroblasts were evaluated using a co-culture system with AKT-siRNA validation. In vivo, a rat fecal-contaminated wound model was established. Therapeutic efficacy, with or without the AKT inhibitor Triciribine, was assessed via laser speckle imaging, histology, and immunofluorescence.

Results

ACGF effectively reprogrammed macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, significantly upregulating CD206 and Arg-1 expression while activating AKT/mTOR signaling. Mechanistically, ACGF-primed macrophages significantly boosted RSF proliferation, migration, and collagen synthesis, effects that were substantially abrogated by AKT silencing. In vivo, ACGF treatment markedly accelerated wound closure, enhanced microvascular perfusion, and increased the density of CD31 + and Ki67 + cells. These regenerative benefits were accompanied by a significant shift toward M2 infiltration and a reduction in pro-inflammatory cytokines, all of which were reversed by pharmacological inhibition of AKT.

Conclusion

ACGF promotes the healing of contaminated wounds by orchestrating an AKT/mTOR-dependent macrophage M2 polarization. This shift initiates a beneficial paracrine relay that enhances fibroblast activity and neoangiogenesis, effectively restoring the regenerative niche. Our findings establish ACGF as a potent immunomodulatory biomaterial and offer a promising therapeutic strategy for complex perianal wounds and chronic recalcitrant defects.