Conjugation of the T1 sequence from CCN1 to fibrin hydrogels for therapeutic vascularization

Publication date: November 2019Source: Materials Science and Engineering: C, Volume 104Author(s): Joana Loureiro, Ana Luísa Torres, Tânia Neto, Paulo Aguiar, Cristina Carvalho Barrias, Marta Teixeira Pinto, Isabel Freitas AmaralAbstractHydrogel matrices with angiogenic properties are much desirable for therapeutic vascularization strategies, namely to provide vascular supply to ischemic areas, transplanted cells, or bioengineered tissues. Here we report the pro-angiogenic effect of fibrin (Fb) functionalization with the T1 sequence from the angiogenic inducer CCN1, forseeing its use in the injured brain and spinal cord. Fibrin functionalization with 40 μM of T1 peptide effectively improved cellular sprouting of human brain microvascular endothelial cells (hCMEC/D3) in the absence of vascular endothelial growth factor (VEGF), without impacting the viscoelastic properties of Fb, cell viability, or proliferation. The pro-angiogenic effect of immobilized T1 was potentiated in the presence of VEGF and partially mediated through α6β1 integrin. The tethering of T1 also enhanced sprouting of human cord blood-derived outgrowth endothelial cells (OEC). Still, to elicit such effect, a higher input T1 concentration was required (60 μM), in line with the lower protein levels of α6 and β1 integrin subunits found in OEC comparing to hCMEC/D3, prior to embedment in Fb gel. Finally, the ability of T1-functionalized Fb in inducing cappilary invasion in vivo was assessed using the C...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research