Table 2 The angiogenic property of nanomaterials in endothelial cells

Inorganic nanomaterials

 Gold

Length 47 ± 0.4 nm, width 14 ± 0.2 nm [14]

Hexagonal morphology, aspect ratio 1:1–1:1.5, length 30 nm [43]

Spherical shape, 22 nm [44]

Spherical shape, 7.6 ± 0.9 nm [38]

(1) Increase cell survival and proliferation of ECs (2) Increase vessel-like structures significantly (3) Increase expression of VEGF, ANG-1, and ANG-2

(1) Delivery system [14, 38] (2) Potent antioxidative effects [43] (3) As an optical switch of biological circuits [14, 44]

 Cu₂S

Nanoparticles, 200–600 nm [36]

Increase blood vascular networks and CD31 positive vessels

Controllable release of Cu ions [36]

 HA

Nanoparticles, < 200 nm [20]

Li doped into the HA, short acicular shapes, < 200 nm [28]

nHA conjugated on the CHO functional groups of PLA scaffold [29]

Nano-rod, micro-arc oxidation-H0.5, 223 nm [154]

Embossed with nanoparticles, 75–250 nm [155]

(1) Improve the viability, adhesion and proliferation of ECs (2) Increase the expression of VEGF, CD31, HIF-1, vWF, VEGFR2, FGF, and ANG-1 (3) Accelerate the tube formation

(1) Delivery system [20, 28] (2) Promote the proliferation and adhesion of ECs at the initial stage [29, 33] (3) Immunomodulatory effects [154, 155]

 TCP

Nanoparticles, 50 nm [21]

(1) Accelerate the proliferation of HUVECs (2) Enhance the secretion of VEGF and the gene expression of VEGF, VEGFR2 and HIF-1α

Promote cell adhesion and proliferation [21]

 Bioactive glass nanoparticle/nanofiber

Sr doped bioactive glass nanofibers [17]

Mesoporous spherical particles, < 300 nm, pore size < 7 nm [30]

440 nm, pore size 2–10 nm [31]

Nanobioglass, ~ 30 nm [39]

(1) Improve the spreading and proliferation of HUVECs (2) More neo-blood vessel formation in CAM model (3) More newly formed blood vessels in vivo (4) Increase CD31 quantity and upregulation of VEGF expression

(1) Si ion release [30, 31, 39] (2) Delivery system [17]

 Zinc oxide nanoflowers/nanoparticles

40–100 nm [111]

60 nm [112]

(1) Increase cell proliferation and DNA synthesis phase of HUVECs (2) Increase the migration of EA.hy926 cells (3) Increase the formation of vascular sprouting in the chick embryo angiogenesis assay (4) More blood vessels formation on the scaffolds in vivo subcutaneous implantation

The generation of ROS [110,111,112]

 Terbium hydroxide rods/spheres

Tb^III(OH)₃, rod shape, diameter 111 ± 18 nm, length 847 ± 165 nm, nanospheres, 106 ± 19 nm [113]

Promote the recovery of intersegmental blood vessels pre-inhibited zebrafish

The generation of ROS [113]

 Europium hydroxide nanorods/spheres

Eu^III(OH)₃, nanospheres, 21 ± 3, rod shape, diameter 36 ± 4 nm, length 215 ± 29 nm [113]

EHN, nanorods, length ~ 150–200 nm, width ~ 40–50 nm [114]

(1) Increase cell viability of HUVECs and EA.hy926 cells (2) New blood vessel formation in chick embryo model (3) Higher tube formation assay of ECV-304 cells

The generation of ROS [113, 114]

 Neodymium

Nanoparticles, nanocubes, nanorods, < 100 nm [98]

(1) Induce tube formation (2) Induction of angiogenesis in vivo CAM and chick aortic arch model assays (3) Activation of VEGF and VEGFR2 pathways

The generation of ROS [98]

 GO

Monolayer thickness < 1 nm, width ~ 20 μm [27]

PEI-GO[49]

GO flakes, height ∼ 1.5 nm [50]

(1) Increase the adhesion, proliferation and migration of HUVECs (2) Form blood vessel like structures (3) The α-SMA, RECA-1, CD-31 positive cells

(1) Containing functional groups as delivery system [50] (2) Protein adsorption [27, 49] (3) M2 macrophage recruitment [27]

 rGO

rGO: C/O ratio 8.6:1, 50 ng/mL, GO: C/O ratio 1.6:1, 10 ng/mL [59]

Porous 3D structure, the ice segregation induced self-assembly technique, wall thickness 40–50 nm [48]

(1) Increase the proliferation of endothelial cells (EA.hy926) in vitro (2) Enhance angiogenesis and thickness of the blood vessels in CAM model (3) RECA-1 and laminin positive staining

(1) Induce a low level of ROS [59] (2) M2 macrophage recruitment [48]

 TiO₂

Highly ordered, vertically oriented TiO₂ nanotubes, diameter 22–300 nm [80]

TiO₂ particles ~ 30–50 nm [81]

Nanotubes, 90 nm [83]

(1) Increase the cell spreading and migration of primary human aortic endothelial cells (2) Decrease the proliferation and expression of collagen I and MMP-2 in primary human aortic smooth muscle cells

(1) Decrease expression of molecules involved in inflammation (2) Sense nanotopographical cues [80, 81, 83]

 Cerium oxide nanoparticle

5–10 nm [116]

Ce³⁺ concentration, 57%/27%, 3–5 nm [117]

(1) Promote viability and proliferation of HUVECs and ECV-304 (2) More blood vessel formation in chick embryo model

(1) Regulate oxygen concentration and activates HIF-1α (2) Reduce oxidative stress [116, 117]

Organic nanomaterials

 Nanofibrin

240 ± 5 nm [24]

Enhance tube formation in vitro

Promote cell adhesion and angiogenesis [24]

 PLLA nanofibrous membrane

Porous PLLA electrospun membranes containing dimethyloxalylglycine loaded mesoporous silica nanoparticles [35]

Stimulate the proliferation, migration of HUVECs

(1) Nanotopology combines aligned electrospun fibers and nanopores can serve as a signaling mechanism to control cell growth and differentiation (2) Avoiding the detachment of nanoparticles (3) Delivery system [35]

 Tetrahedral DNA

Triangular nanoparticles, formed by four ss-DNAs fragments [137]

(1) Promote the proliferation, migration and tube formation of ECs (2) Increase the expression of VEGFA, VEGFR2

Low biotoxicity, nuclease resistance, relative stability and programmability [137]