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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Loureiro, J (Author) Other; Torres, AL (Author) Other; Neto, T (Author) Other; Paulo Aguiar (Author) FMUP; Barrias, CC (Author) Other; Pinto, MT (Author) Other; Amaral, IF (Author) Other

Journal

Title: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS

Vol. 104

ISSN: 0928-4931

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00Q-T3P

DOI: 10.1016/j.msec.2019.109847

Abstract (EN): Hydrogel 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 mu M 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 alpha 6 beta 1 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 mu M), in line with the lower protein levels of alpha 6 and beta 1 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 CAM assay, which evidenced a significant increase in the number of newly formed vessels at sites of implantation of T1-functionalized Fb, in the absence of soluble angiogenic factors. Overall these results demonstrate the potential of T1 peptide-presenting gels for use In therapeutic vascularization approaches. Considering T1 neurite-extension promoting capability and pro-angiogenic properties, T1-functionalized Fb hydrogels are particularly promising for application in the injured central nervous system.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10