Table 1.

Summary of the hydrogel-based regulation strategies on immunomodulation

Property	Hydrogel example	Cell function	References
Dimensionality	Agarose gel	3D induced monocytes differentiation	[94]
	Collagen gel	3D promoted M2 polarization in inflammatory condition	[93]
Stiffness	Transglutaminase cross-linked gelatin gel (1.58 and 60.54 kPa)	Macrophages polarization Stiffer-induced M1 markers Softer-induced M2 markers	[108]
	PEG-RGD hydrogel (130, 240 and 840 kPa)	Inflammatory cytokines secretion by macrophages Stiffer promoted higher pro-inflammatory cytokines	[106]
	Polyacrylamide gel (11, 88 and 323 kPa)	Phagocytosis and migration of macrophages Softer induced highly phagocytic and migratory phenotype	[107]
	Polyacrylamide gel (10, 25, 100 and 200 kPa)	T lymphocytes activation Stiffer induced fast migration, pro-inflammatory factor expression, and aerobic glycolysis	[111–113]
	Polyacrylamide gel (2.6, 7.4 and 22.1 kPa)	B lymphocytes activation Stiffer promoted accumulated BCR and high expressed CD69	[114]
Porosity	Alginate hydrogel	50% porosity allowed more DCs infiltration	[119]
	Poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel	40-µm pore size induced M2 polarization	[123]
Topography	Polyacrylamide hydrogel	Nano-pattern induced low level of FBR	[127]
	Gelatin methacryloyl hydrogel	Microgrooved pattern promoted M2 marker expression and phagocytosis	[43]
Wettability	Methacrylated gellan gum hydrogel	Hydrophobicity induced high M1 marker expression and low phagocytosis	[44]
Electric property	Alginate/PEI hydrogel/multidomain peptide (MDP) hydrogel	Positive charge elicited high level of FBR	[144, 145]
Molecular presentation	Decellularized matrices	Macrophages polarization depended on tissue source of decellularized matrices	[146]
	ECM molecules	Lower expression of pro-inflammatory factors by monocytes M2 polarization	[21, 151]
	Peptides	Recruitment of neutrophils and macrophages Decrease of inflammatory factor expression by macrophages	[134, 155, 158, 159]