Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (在线): 1-13.

   

Biomimetic Black Phosphorus Nanosystem Regulates Synovial Macrophage Polarization for Osteoarthritis Treatment

Yu Cenqi, Liu Yang, Yu Jiangfeng, Kang Kang,Deng Yaoge, Xia Xiaowei, Zhang Yijian, Zhu Xuesong   

  1. Department of Orthopedics, First Affiliated Hospital of Soochow University, Institute of Orthopedics of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Received:2025-09-27 Revised:2026-01-07 Online:2026-01-01 Published:2026-02-03

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Abstract: BACKGROUND: Existing studies suggest that the imbalance in synovial macrophage polarization and extracellular matrix degradation are key factors in OA progression. Under NIR irradiation , BPNs generate a mild photothermal effect to inhibit inflammation, but they lack targeting specificity. The M2 macrophage membrane coating significantly enhances the targeting and immunoregulatory functions of BPNs.
OBJECTIVE: To investigate the therapeutic effect of M2M@BPNs combined with NIR intervention on OA.
METHODS: (1) M2M@BPNs were prepared, and their morphology, hydrated particle size, and photothermal properties were characterized, followed by evaluation of their in vitro and in vivo biocompatibility. (2) In vitro, the combined treatment of M2M@BPNs and NIR irradiation was assessed for its effects on CD86, iNOS, CD206, and Arg-1 mRNA expression, and on CD86 protein expression in LPS-induced macrophages. Conditioned media from each group were collected to assess their impact on chondrocytes, including mRNA expression of aggrecan, type II collagen COL II, matrix MMP 13, and a disintegrin and ADAMTS 5, as well as MMP 13 protein expression, and on fibroblasts, including mRNA expression of type I collagen COL I, type III collagen COL III,α-SMA, and COL I protein expression. Cartilage formation was evaluated using microsphere culture, and cell migration was assessed by scratch assays. (3) In vivo, we established an OA model by transecting the medial meniscotibial ligament and evaluated the effects of M2M@BPNs combined with NIR irradiation on knee joint histology and the expression of CD86, CD206, COL II, and MMP-13.
RESULTS AND CONCLUSION: (1) M2M@BPNs exhibited an ultrathin nanosheet morphology with an average particle size of 184.76±0.46nm, stably increasing temperature by 6°C under NIR irradiation, and demonstrated good photothermal stability and biocompatibility. (2) In vitro, M2M@BPNs combined with NIR significantly decreased CD86 and iNOS expression and increased CD206 and arginase-1 expression, promoting M2 polarization in macrophages. Conditioned media from these macrophages enhanced aggrecan and type II collagen expression, reduced MMP-13 and ADAMTS-5 levels to facilitate cartilage formation, and decreased type I collagen, type III collagen, and α-SMA expression to inhibit fibroblast migration. (3) In vivo, M2M@BPNs combined with NIR improved cartilage structure, preserved proteoglycan, reduced CD86 and MMP-13 expression, increased CD206 and type II collagen expression, and alleviated synovial hyperplasia and OA degeneration. These results indicate that M2M@BPNs combined with NIR can regulate macrophage polarization, indirectly maintain chondrocyte and fibroblast homeostasis, and exert a protective effect against OA.

Key words: Cell membrane modification, Black phosphorus nanosheets, Photothermal therapy, Macrophage polarization, Osteoarthritis, Matrix metabolism, Near-infrared (NIR) irradiation

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