Table 2.

Effect of stiffness modulation on the different steps of angiogenesis. (+ = increased angiogenesis, − = decreased angiogenesis).

Step of Angiogenesis	Stiffness Modulation	Effect on Angiogenesis	Involved Stiffness Factors
Cell-Matrix contact/adhesion	Increased stiffness increases adhesion	+	Kind of ECM protein Concentration
Cell migration	Increased stiffness enhances migration	+	Kind of ECM protein Concentration Intrinsic tension Degradability Remodeling
	Stiffness gradients determine migration direction	+
	Excessively high stiffness increases the mechanical barrier and reduces migration	−
Tip/stalk cell selection	Increased stiffness enhances proliferation of stalk cells	+/− (longer sprouts, less branching)	Concentration Synthesis Degradability Remodeling
	Stiffness gradient promotes tip cell migration	+
Vessel stabilization	Increased stiffness reduces cell–cell contacts and promotes EC permeability	−	Kind of ECM protein Concentration Crosslinking Synthesis Remodeling
	Higher stiffness enhances the mural cell recruitment to support EC	+