Table 5 Summary of advanced biomaterials for sequential regulation of transition from M1 to M2 state

Multifunctional injectable microspheres

SA and Gp-cross-linked Gel incorporated with TA and copper ions (Cu²⁺)

RAW264.7 cells and BMSCs

Rat osteomyelitis model

M1 polarization

In vitro: (1) The release of Cu²⁺ promotes M1 macrophage polarization and upregulates the expression of pro-inflammatory factors; (2) The release of Cu²⁺ can also induce bacterial DNA damage, achieving an antibacterial effect.

In vivo: It induces M1 macrophage polarization to clear Staphylococcus aureus at 3 weeks.

M2 polarization

In vitro: (1) The release of TA promotes M2 macrophage polarization, upregulates the expression of anti-inflammatory factors, and facilitates the osteogenic differentiation of BMSCs; (2) The release of TA also exhibits significant antibacterial and antioxidant functions.

In vivo: It induces M2 macrophage polarization to promote bone tissue repair and regeneration at 6 weeks.

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Functionalized PEEK

PEEK, CS-BGNs, PDA

RAW264.7 cells and rBMSCs

Mice implant-related osteomyelitis model

M1 polarization

In vitro: (1) The rapid release of outer-layer Cu²⁺ induces M1 macrophage polarization, facilitating early antibacterial activity; (2) It promotes early osteogenic differentiation.

M2 polarization

In vitro: (1) The slow release of inner-layer Sr²⁺ promotes M2 macrophage polarization, alleviating inflammatory responses; (2) It enhances mid-to-late-stage osteogenic differentiation and bone mineralization.

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Microsphere−Gel composite system

Porcine SIS hydrogel, LL37 peptides, PLGA microspheres, WP9QY (W9) peptide

RAW264.7 cells and BMSCs

Rat model of bone defect

M1 polarization

In vitro: (1) The release of LL37 peptides promotes M1 macrophage polarization, providing early infection prevention; (2) The release of LL37 peptides also increases the number of BMSCs.

In vivo: It induces M2 macrophage polarization to promote bone tissue repair and regeneration at 1 month.

M2 polarization

In vitro: (1) The release of W9 peptides promotes M2 macrophage polarization, alleviating inflammatory responses; (2) The release of W9 peptides also enhances the osteogenic differentiation of BMSCs.

In vivo: It mildly induces M1 macrophage polarization but does not affect the final osteogenic outcome.

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Cubic multi-ions-doped Na₂TiO₃ nanorod-like coatings

Ca²⁺, Mg²⁺, Sr²⁺, Zn²⁺, Na₂TiO₃ nanorod-like coatings

RAW264.7 cells, HUVECs, and rBMSCs

Rat implant-related model

M1 polarization

In vitro: Ion release induces M1 macrophage polarization, promoting angiogenesis by acting on endothelial cells.

In vivo: It induces M1 macrophage polarization and enhances angiogenesis.

M2 polarization

In vitro: Ion release induces M2 macrophage polarization, promoting osteogenic differentiation.

In vivo: It induces M2 macrophage polarization and facilitates vascularized osteogenesis.

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Scaffolds based on decellularized bone

IFN-γ, IL4, decellularized bone scaffolds

Monocyte-derived macrophages

Mice model of subcutaneous implantation

M1 polarization

In vitro: The short-term release of IFN-γ induces M1 macrophage polarization, promoting VEGF expression and vascular infiltration.

In vivo: It enhances angiogenesis, while no differences are observed in macrophage phenotype.

M2 polarization

In vitro: The sustained release of IL-4 induces M2 macrophage polarization, further promoting the secretion of PDGF-BB and angiogenesis.

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