Table 1 Representative studies illustrating how nanopores affect macrophage polarization

Layer-by-layer (PEEK surfaces, several tens of nanometers and 200–500 nm)

RAW 264.7, THP-1 and BMSCs

Sprague Dawley rats

Spherical shape with a few pseudopodia

↓IL-6, IL-1β

↓TNF-α

↓iNOS, nitric oxide (NO)

↑CD206

↑TGF-β1, BMP2 ↑VEGF

M2

[103]

Anodization (Alumina membranes, 15–200 nm)

RAW 264.7 and rat BMSCs

0-100 nm: become rounder and less pseudopodia with increasing diameter

200 nm: a less rounded shape and more pseudopodia

↓CD86, CD11c, CCR7

↓IL-18, IL-1β, IL-6

↓TNF-α

↓ROS (100, 200 nm)

↓iNOS

↓Oncostatin-M

↑CD206

↑IκB

M2, especially on larger sized nanopores

[105]

PS sphere template scarification and TiO₂ crystallization (90-5000 nm)

RAW 264.7 and BMSCs

Sprague-Dawley rats

90, 500 nm: abundant filopodia

Micrometer scale: less cellular protrusion

↓CCR7

↓IL-1α, TNF-α (90, 500 nm)

↑CD206 (90, 500 nm)

↑IL-4, IL-10 (90,500 nm)

M2 on 90, 500 nm

[19]

Chemical etching (Ti, oxidizing solution, 20–22 nm)

U937 (human leukemia cells)

More rounded morphology with long filopodia

↓IP10 (CXCL10) ↓MIP3α (CCL20)

↑MCP-1 (CCL2)

↓OPN

↓SPARC/ stabilin 1 (subtle change)

N/A

M2-like

[110]

Anodization (TiZr alloy, 35 nm diameter and 3.2 μm length)

RAW 264.7

more rounded and smaller spread areas

↓TNF-α

↓MCP-1 (after LPS stimulation)

N/A

M2-like

[104]

Anodization (Alumina membranes, 20 and 200 nm)

RAW 264.7 and NIH 3T3

BALB/C mice

20 nm: round

200 nm: more elongated and flattened

↑IL-13, IL-1β, IL-6, IL-9, IL-2 (200 nm)

↑ROS (200 nm)

N/A

M1-like on 200 nm

[106]

Alkali-hydrothermal treatment (Ti, Ra = 0.45 ± 0.03 μm)

THP1 (human monocytic cells)

No difference compared to smooth Ti surfaces

No difference in the expression of CCR7 compared to smooth Ti surfaces

No difference in the expression of CD206 compared to smooth Ti surfaces

No difference compared to smooth Ti surfaces

[111]