Table 1.
Microenvironment-targeted strategy.
Types | Pathway | Materials | Function | Ref. |
---|---|---|---|---|
Physiological Microenvironment | Immunomodulation | Titanium implant | Micro-rough and hydrophilic surfaces promote the release of anti-inflammatory factors from macrophages | [81] |
Polyethylene terephthalate | Macrophages adhering to hydrophilic and anionic surfaces selectively produce anti-inflammatory cytokines | [82] | ||
Magnesium containing microspheres | Mg2+ release upregulates anti-inflammatory genes and triggers immune regulation | [83] | ||
miR-181b exosomes | Exo-181b activates the PRKCD/AKT signaling pathway to promote M2 polarization | [84] | ||
Angiogenesis | Sulfated chitosan scaffold | Dual-module scaffold continuously releases rhBMP-2 and VEGF, synergistically promoting osteogenesis and angiogenesis | [85] | |
Nanofibrous gelatin-silica hybrid scaffold | Vascular-mimicking microchannel scaffold promotes rapid vascularization and bone regeneration | [86] | ||
Energy metabolism | Bioenergetic-active material scaffold | Scaffold degradation fragments can increase mitochondrial membrane potential to accelerate bone regeneration | [87] | |
GelMA hydrogel | Mg2+ increases cellular bioenergy levels to promote osteogenesis induction | [88] | ||
Citrate composite support | Citrate-mediated elevation of cellular energy levels supports metabolic osteogenesis | [89] | ||
Chemical Microenvironment | Oxygen | Liposomal/hydrogel complexes | ROS-responsive hydrogel releases oxygen to promote bone regeneration | [90] |
PCL/nHA/CaO2 scaffold | The bionic scaffold releases oxygen continuously to promote bone defect repair | [91] | ||
Bioactive glass/collagen–glycosaminoglycan scaffold | Co2+ mimics hypoxic signaling to activate the HIF pathway to support osteogenesis | [92] | ||
pH | MOF@CaP nanoplatform | Nanoplatform mimics low pH environment to enhance bone regeneration and capacity | [93] | |
Custom Titanium implant | The alkaline microenvironment mediates the osteogenic differentiation of stem cells and promotes new bone formation | [94] | ||
Enzymes and Cytokines | Chondroitin Sulfate/Polyethylene Glycol hydrogel | Matrix metalloproteinase-mediated degradation of hydrogels regulates stem cell differentiation | [95] | |
GelMA hydrogel | Mineralized alkaline phosphatase enhances the osteogenic differentiation potential of BMSCs | [96] | ||
Hyaluronic acid hydrogel | Nanozymes mediate O2 production from endogenous H2O2 and provide a microenvironment for osteogenesis | [97] | ||
Physical Microenvironment | Mechanical forces | Polydimethylsiloxane substrates | Stiff materials have a higher osteogenic potential than soft materials | [98] |
The flow loop apparatus | Sustained low-velocity shear stress stimulates the expression of osteogenic markers in stem cells | [99] | ||
Gelatin hydrogel | Reversibly connected, highly elastic hydrogel adapts to dynamic stresses and supports bone regeneration processes | [100] | ||
Temperature | light-responsive poly (N-isopropylacrylamide- co -nitrobenzyl methacrylate) | Ultraviolet light stimulates the release of dexamethasone from photosensitive materials to promote bone regeneration | [101] | |
Poly (vinyl alcohol) fibers | Thermoresponsive fibers improve the toughness of calcium phosphate cement and enhance bone repair | [102] | ||
Biphasic calcium phosphate scaffold | Regulates drug release by changing the light source wavelength to promote bone repair | [103] | ||
Electric field | Whitlockite scaffold | Scaffolds provide an endogenous electric field to the defect site and inhibit the activity of osteoclasts. | [104] | |
Triboelectric nanogenerator | Mediated proliferation and differentiation of osteoblasts by electrical stimulation | [105] | ||
Magnetic field | Poly(lactide-co-glycolide) scaffold | Magneto-thermal accelerated degradation behavior of magnetic scaffolds under alternating magnetic fields | [106] | |
Static magnetic field | Magnetic fields can regulate the direction of osteoblast growth | [107] | ||
Acoustic | Collagen sponge | In situ recruitment of osteogenic factors by ultrasonically shocked microbubbles | [108] | |
Acoustically responsive scaffold/hydrogel | Pulsed ultrasound recruits BMSCs for bone repair | [109] | ||
Programming design | Poly(aryl-ether-ether-ketone) (PEEK) implant | Programmed surface coating to release osteogenic drugs over time | [110] | |
GelMA hydrogel | Programming a two-factor delivery system to match the bone repair healing process | [111] |