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. 2023 Jul 21;22:100741. doi: 10.1016/j.mtbio.2023.100741

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]