Table 3 Summary of advanced biomaterials for modulating macrophage anti-inflammatory polarization in acute bone infections

From: Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment

Types of biomaterials

Major components

In vitro model

In vivo model

Macrophage polarization

Functions

Ref.

Titanium-based biomaterials

Ti, antimicrobial peptide (HHC36), MSNs

RAW 264.7 macrophages, mouse BMSCs

Rabbit model of infection bone defect

M2 polarization

In vitro: (1) Excellent antibacterial performance; (2) The biomaterial induces M2 macrophage polarization to activate anti-inflammatory responses; (3) Promotes osteogenic activity and exhibits good biocompatibility.

In vivo: (1) It inhibits bacterial infections; (2) Induces M2 macrophage polarization for anti-inflammatory effects and enhances bone integration.

285

Ti, ZIF-8, honeycomb-like TiO2 nanotube array (TNT)

RAW264.7 cells and BMSCs

Rat implant-associated infection model

M2 polarization

In vitro: (1) The glucose oxidase activity of ZIF-8 promotes antibacterial effects; (2) Zn²⁺ release hydrolyzes extracellular DNA, enhancing bacterial killing and preventing biofilm formation; (3) It promotes osteogenic differentiation; (4) Induces macrophage M2 polarization and inhibits the overexpression of pro-inflammatory factors.

In vivo: (1) Bacterial eradication; (2) It induces M2 macrophage polarization and promotes bone integration.

286

Ti, hydrogel coating composed of konjac gum and gelatin, tannic acid-d-tyrosine nanoparticles

RAW264.7 cells and MSCs

Rat implant-associated infection model

M2 polarization

In vitro: (1) Excellent photothermal effects synergize to kill bacteria and eliminate biofilms; (2) The biomaterial removes excessive intracellular ROS and induces macrophage M2 polarization, reducing pro-inflammatory responses; (3) Promotes MSC proliferation and osteogenic differentiation.

In vivo: (1) Bacterial eradication; (2) It induces M2 macrophage polarization, alleviates inflammatory responses, and promotes bone integration.

287

Ti, bioactive polydopamine/Ti3C2/poly(vinylidene fluoride trifluoroethylene) (PDA/Ti3C2/P(VDF-TrFE)) nanocomposite

RAW264.7 cells and MSCs

/

M2 polarization

In vitro: (1) The biomaterial directly promotes the spreading, growth, and differentiation of BMSCs; (2) Thermal stimulation enhances HSP47 synthesis and activates the MEK/ERK pathway to promote osteogenic differentiation; (3) Mild thermal stimulation induces macrophage M2 polarization, reducing inflammatory responses; (4) Excellent antibacterial properties.

288

Ti6Al4V-6Cu alloy

RAW264.7 cells, HGFs, HUVECs, and osteoblasts

/

M2 polarization

In vitro: (1) The biomaterial promotes angiogenesis in HUVECs; (2) Induces macrophage M2 polarization, reducing inflammatory responses; (3) Excellent biocompatibility.

289

Ti6Al4V-6Cu alloy

Osteoporotic macrophages

/

M2 polarization

In vitro: The biomaterial induces M2 polarization of osteoporotic macrophages in an infected microenvironment, promoting the release of anti-inflammatory factors.

290

PEEK-based biomaterials

PEEK, polydopamine-bioactive glass nanoparticles

RAW264.7 cells, BMSC, MC3T3-E1 cells, and ADSCs

Rat model of bone defect

M2 polarization

In vitro: (1) Excellent photothermal antibacterial activity; (2) The biomaterial promotes osteogenic differentiation of BSMCs; (3) Induces macrophage M2 polarization and reduces the expression of inflammatory factors.

In vivo: It induces macrophage M2 polarization and promotes bone integration.

294

PEEK, PDA, GS layer

MC3T3-E1 and RAW264.7 cells

Rat implant-associated infection model

M2 polarization

In vitro: (1) Excellent activity in promoting osteogenic differentiation; (2) The biomaterial induces macrophage M2 polarization; (3) Exhibits excellent antibacterial properties.

In vivo: It induces macrophage M2 polarization and promotes bone integration.

295

3D porous sulfonated PEEK, sodium butyrate

RAW264.7 cells and rat BMSCs

Rat osteomyelitis model

M2 polarization

In vitro: (1) Enhanced macrophage phagocytic activity and elevated ROS levels promote bacterial eradication; (2) The biomaterial induces macrophage M2 polarization and stimulates the secretion of anti-inflammatory cytokines; (3) Exhibits excellent osteogenic activity.

In vivo: (1) Excellent anti-infection capability; (2) Good bone repair capability.

296

Metal/metal oxide NPs

Ti, Ag NPs, Sr

MC3T3-E1 cells and RAW264.7 cells

Rat model of infected femoral metaphysis

M2 polarization

In vitro: (1) The biomaterial eliminates pathogens through the release of Ag⁺ and Sr²⁺ and promotes osteoblast. differentiation; (2) It induces macrophage M2 polarization.

In vivo: Enhanced bone integration performance.

300

50 nm Au NPs

RAW264.7 cells and BMSCs

Rat osteomyelitis model

M2 polarization

In vitro: (1) The biomaterial induces macrophage M2 polarization by inhibiting the NF-κB signaling pathway; (2) It promotes osteogenic differentiation of BSMCs; (3) Overexpression of TREM2 enhances macrophage phagocytosis of Staphylococcus aureus.

In vivo: It suppresses inflammatory responses, and promotes tissue repair.

303

Lipopolysaccharide-treated macrophage cell membranes, AuNC

RAW264.7 cells

Mice model of bone defect

M2 polarization

In vitro: (1) Nanoparticles synergize with photodynamic therapy for antibacterial effects and remove residual ROS; (2) It induces macrophage M2 polarization

In vivo: It induces macrophage M2 polarization, suppresses inflammatory responses, and promotes bone repair.

304

CeO2 nanoceria, Ce6

RAW264.7 cells and MC3T3-E1cells

Rat models of periodontal inflammation

M2 polarization

In vitro: The biomaterial promotes macrophage M2 polarization and enhances anti-inflammatory responses.

In vivo: It induces macrophage M2 polarization, suppresses inflammatory responses, and promotes tissue repair.

307

ZnO nanowires, collagen fibrils

RAW264.7 cells and BMSCs

Rat model of infectious mandibular defect

M2 polarization

In vitro: (1) The biomaterial promotes BMSC adhesion, proliferation, and osteogenic differentiation; (2) It releases Zn²⁺ to inhibit bacterial activity.

In vivo: It induces macrophage M2 polarization, suppresses inflammatory responses, and promotes the healing of infected bone defects.

308

Borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4)

RAW264.7 cells and MSCs

Rabbit model of implant-related S. aureus bone infection

M2 polarization

In vitro: (1) The biomaterial promotes MSC osteogenic differentiation and mineralization; (2) Induces macrophage M2 polarization and upregulates the expression of anti-inflammatory factors.

In vivo: It completely eradicates bacteria while facilitating new bone formation.

309

Nanocomposites

Chitosan, puerarin

rBMSCs

Air pouch model, and rat model of femoral osteomyelitis

M2 polarization

In vitro: (1) Excellent antibacterial properties; (2) It rBMSC proliferation and osteogenic differentiation.

In vivo: (1) The biomaterial removes LPS and regulates macrophage M2 polarization; (2) It improves bacterial infection-induced bone destruction.

317

Biomimetic nanocomposites enabled loading of antibiotics (gentamicin and doxycycline)

hMSCs and THP-1

/

M2 polarization

In vitro: (1) Excellent antibacterial properties; (2) The biomaterial facilitates hMSC adhesion and osteoinduction; (3) Promotes macrophage M2 polarization

318

ZIF-8, BPNs, GelMA, HAMA

MC3T3-E1 cells and RAW 264.7 cells

Rat model of severe cranial defect

M2 polarization

In vitro: (1) The biomaterial promotes macrophage M2 polarization and inhibits inflammatory responses; (2) Enhances osteogenic differentiation; (3) Photothermal antibacterial activity.

In vivo: It achieves multiple functions, including antibacterial, anti-inflammatory, and bone regeneration promotion.

319

  1. ADSC Adipose-derived stem cells, Ag NPs Silver nanoparticles, AuNC Gold nanocage, Au NPs Gold nanoparticles, BMSCs Bone marrow-derived mesenchymal stem cells, BPNs Black phosphorus nanosheets, Ce6 Chlorin e6, GelMA Gelatin methacryloyl, GS Gentamicin sulfate, HAMA Hyaluronic Acid Methacryloyl, HGFs Human gingival fibroblasts, HSP47 Heat shock protein 47, HUVECs Human umbilical vein endothelial cells, MEK Mitogen-activated protein kinase kinase, MSNs Mesoporous silica nanoparticles, PDA Polydopamine, PEEK Polyether ether ketone, ROS Reactive oxygen species, TNT Titanium nanotube array, TREM2 Triggering receptor expressed on myeloid cells 2, ZnO Zinc oxide, ZIF-8 Zeolitic imidazolate framework