Table 2.

Responses of macrophage mediated by the physicochemical properties of biomaterials in vivo and vitro.

properties of biomaterials		macrophage responses		reference
biomaterial size	poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) (5–7 μm), nanoparticles (PLGA-NPs) (389 nm)	in vitro	MPs > NPs: stimulated TNF-α and IL-1β in J774 macrophages.	[218]
	endotoxin-free intermediate chitin (40–70 μm), small chitin (<40 μm)	in vivo	intermediate chitin > small chitin: stimulated TNF production. Only small chitin particles stimulated IL-10 production in WT C57BL/6 mice lung macrophages.	[219]
geometric construction	endotoxin-free Ch powder in two geometries: ChO (with orthogonal struts), ChD (with diagonal and orthogonal struts)	in vitro	ChO > ChD: TNF-αand IL-12/23 in human monocytes isolated from healthy donors.	[220]
	subcutaneous implantation: 3D Poly ε-caprolactone (PCL) nanofiber, 2D nanofiber scaffolds	in vivo	3D > 2D: macrophage infiltration, M2/M1 ratio after 4 weeks of implantation into 9-week old Sprague Dawley (SD) rats.	[221]
composition	gelatin methacryloyl (GelMA) and poly (ethylene glycol)diacrylate (PEGDA) hydrogels	in vitro	GelMA > PEGDA hydrogels: CD206 expression in THP-1 cells PEGDA > GelMA hydrogels: CD86 expression in THP-1 cells	[222]
	coiled-coil (CC)- and Ca2+-crosslinked alginate hydrogels	in vivo	Ca2+- > CC-crosslinked gels: released IL-1β following LPS stimulation in female C57BL6/J mice peritoneal macrophage.	[223]
surface modification	amines (NH2), carboxylic acids (COOH) and phosphonic acids (PO3H2) modified poly (styrene) (PS) surface	in vitro	Substrates modified with COOH resulted in an increase in IL-10 secretion and CD206 expression but did not alter either TNF-α secretion or CD80 expression in THP-1-macrophage.	[224]
	polyetheretherketone (PEEK), sulfonated (SPEEK) and zinc-coated SPEEK scaffolds	in vivo	Zn-coated SPEEK > PEEK, SPEEK scaffolds: M2 (F4/80+CD206+)/M1 (F4/80+CCR7+) proportion subcutaneous implantation in C57BL/6 mice.	[225]
topography	smooth Ti and rough Ti surface	in vitro	smooth Ti > rough Ti: pro-inflammatory/anti-inflammatory phenotype in primary murine macrophages.	[226]
	bulk metallic glasses (BMGs) and BMGs with 55 nm nanorod arrays (BMG-55)	in vivo	BMG-55>flat BMG: the ratio of Arg-1/iNOS expression in macrophages of tissues surrounding after 2 weeks in C57BL/6 mice aged 9–12 weeks.	[227]
stiffness	transglutaminase cross-linked gelatins (TG-gels): degrees of matrix stiffness	in vitro	matrix stiffness (high > mid > low): M1-associated markers (IL-1β and TNF-α) in RAW264.7 cells	[228]
	methacrylate–gelatin (GelMA) hydrogel: low-, medium-, high-stiffness (2, 10, and 29 kPa)	in vivo	high-stiffness > medium- and low-stiffness hydrogel implants: M1/M2 proportion low-stiffness > medium- and high-stiffness hydrogel implants: M2/M1 proportion in BALB/c 6-week-old male mice.	[229]
dynamic physicochemical changes	PEG hydrogels: homogeneous surface to a dynamic Arg-Gly-Asp (RGD)-patterned surface upon UV exposure	in vitro	After exposure to UV radiation: iNOS+ IL-10lo M1 transformed to the Arg-1+ IL-10hi M2 phenotype in mouse BMDMs.	[230]
	shape-memory PEG-modified gold nanorods (AuNRs)/PCL films (SMPs):flat surface to micro-grooved surface after near-infrared (NIR) irradiation	in vivo	upon exposure to NIR: iNOS+IL-10lo macrophages to the Arg + IL-10hi phenotype in Sprague Dawley (SD) rats.	[231]
degradation products	Mg-based implants generate a range of bioactive substances, including degradation particles (DPs), 200, 400, 800 and 1600 μg/ml generated from Mg via electrochemical corrosion	in vitro	stimulated with DPs(1600 > 800>400 > 200 μg/ml): CD86+M1/CD206+M2 proportion in RAW264.7 cell line.	[232]
	Zn-based porous scaffolds (incorporating 0.8 wt% Li): isotropic minimal surface G unit and anisotropic BCC unit	in vivo	isotropic minimal surface G unit > anisotropic BCC unit: degradation rate and promoting macrophage polarization toward an anti-inflammatory phenotype in 12-week-old male Sprague-Dawley rats weighing 350–400 g.	[233]