Cell and material interactions: matrix remodeling. (A) Viscoelasticity measurements revealed a decrease in hydrogel stiffness along the 3-day culture period, reaching 40 Pa in hydrogel encapsulated with ECFCs. (B) Real-time RT-PCR analysis shows increased expression of (i) MT1-MMP, MMP-1, MMP-2, Hyal 2, and Hyal 3 and (ii) TIMP-1, TIMP-2, TIMP-3, of encapsulated ECFCs along the 3-day culture period. Significance levels were set at: #P > .05, *P < .05, and **P < .01. (C) ECFCs undergo vascular morphogenesis in the absence (positive control) or presence of 5 μg/mL TIMP-1, TIMP-2, or TIMP-3. The presence of TIMP-1, TIMP-2, or TIMP-3 blocked tubulogenesis, as it did to the negative control (in the presence of 5μM GM6001). (D) siRNA suppression of MT1-MMP allowed vacuole formation and some extent of branching without luminal structures, while suppression of Hyal-2 or Hyal-3 did not affect vascular morphogenesis. Scale bars are 100 μm (left panel) and 10 μm (right panel).