Table 1 A partial composite hydrogel strategy for treating infectious bone defects

Gelatin methacrylate (GelMA)

β-TCP;

Sodium alginate

(Alg);

Strontium chloride (Sr²⁺);

MXenes (Ti₃C₂)

Photothermal Therapy (PTT)

Osteogenic Stimulation

Vitro: Significant inhibition against S. aureus and E. coli (Viability Reduction: 1.4% and 1.1%)

Vitro: mRNA expression levels of Runx2, ALP, and OCN↑;

ALP activities and protein expression levels of ALP and OPN↑;

Vivo: Micro-CT showed Bone volume/Tissue volume (BV/TV) ratios↑;

H&E staining: Direct connection of new bone with host bone;

Immunohistochemical staining: ALP and OCN↑

2022[241]

GelMA

N-acryloyl glycinamide (NAGA);

Molybdenum Disulfide (MoS₂);

Gadolinium (Gd)

PTT;

Tumor Ablation

Vitro: Effective antibacterial activity against S. aureus and E. coli

Vivo: Bacterial infections and inflammation↓

(S. aureus-infected rat tibia defects)

Osteogenic Differentiation: Gd³⁺ ions promoted osteogenic differentiation of rat osteoblasts (ROBs);

Bone Regeneration:

1. Micro-CT and histological analysis: Significant New bone formation;

2. Quantitative data: BV/TV (11.83%);

3. Fluorochrome-labeling: 6.85% (12 weeks)

2023[242]

GelMA

Copper ion-modified germanium phosphorus nanosheets (GeP@Cu);

Gd

Conductivity and Biodegradability

Antibacterial rates of 95.51% ± 2.15% (E. coli) and 94.28% ± 4.16% (S. aureus);

ROS Generation

1.Osteogenic Differentiation of BMSCs, ALP activity and mineralized matrix formation↑;

2. Neurogenic Differentiation and Angiogenesis↑;

3. Micro-CT: BV/TV and trabecular number (Tb.N) after 12 weeks↑

2023[243]

GelMA

Proanthocyanidin;

Amikacin;

Boronate Complexes

Dual Delivery System;

pH and ROS Responsiveness;

Antibacterial rates of S. aureus and E. coli were 87.4% and 78.4%;

Bacterial Morphology: Damaged bacterial morphology

ALP activity and gene expression levels of Alp, Runx2, OCN, and Col1↑

2024[244]

Carboxymethyl Chitosan (CMCS);

GelMA

BMP−2;

PLGA;

GO;

Antisense yycF (ASyycF)

Photo-crosslinking;

Spring Structure

Antibacterial property of composite hydrogel 20 times higher;

Biofilm formation (S. aureus) ↓;

Vitro: ALP (7 days) and Alizarin Red staining (14 days) ↑;

Vivo: 1. Large amounts of new osteotylus formation and effective infection control (8 weeks); 2. Micro-CT: nearly complete healing of the bone defect; 3. Histopathological Analysis: Deposition of collagen and new bone formation

2023[245]

CS

Sulfated-(SCS)

Oxidized HA;

β-Sodium Glycerophosphate (β-GP);

Cu-Sr Doped Mesoporous Bioactive Glass (CuSrMBG)

Dual-Network Formation

1.Vitro: Number of E. coli and S. aureus↓ (> 95%);

2.M1 → M2

Osteogenic Differentiation: ALP and mineral deposition↑;

Bone Regeneration: BV/TV, bone mineral density (BMD), trabecular structure↑

2024[246]

Aldehyde hyaluronic acid (AHA);

Carboxymeth-yl chitosan (NOCC)

PCL; Van;

Mesoporous silica nanoparticles (MSNs);

Fingolimod (FTY720)

Dual-Drug Delivery;

Structural Support

Vitro: Scaffolds showed strong growth inhibition against S. aureus and E. coli

1.The scaffold supported BMSCs growth;

2. ALP activity and calcium nodule formation↑

3. Vivo: BV/TV and Trabecular Thickness (Tb.Th)↑

2023[247]

Gellan Gum (GG)

HAp;

Chlorhexidine

Injectable Delivery System

Significant inhibition of S. aureus biofilm formation was observed at a concentration of 50 mg/mL;

Lower bacterial colony counts in infectious bone defects

New Bone Formation at 4,8 weeks↑;

Micro-CT: Value of BV/TV were 0.32 ± 0.11 (4 weeks) and 0.49 ± 0.13 (8 weeks)

Histological Analysis: Defect areas largely consisted of blue-stained newly formed woven bone, indicating active bone regeneration

2022[248]

Polyethylene Glycol Diacrylate (PEGDA)

Copper (Cu)-Strontium (Sr) Peroxide Nanoparticles (CSp NPs)

Dual Metal Peroxides;

pH-Responsive Release (Ph = 5.5: Antibacterial activity

pH = 7.4: Osteogenesis)

Vitro: IC50 of S. aureus was 25 ± 0.796 μg/mL; A killing rate of 99.94% at 50 μg/mL

Vivo:

Proliferation and Osteogenic Differentiation of BMSCs↑;

Expression of Alp, Bsp, and OCN↑;

Bone Regeneration: Complete filling of bone defects with new bone (21 d), BV/TV and BMD↑

2024[249]