Integrin-specific hydrogels for growth factor-free vasculogenesis

Autores da FMUP

• Ricardo José Moreira Horta Oliveira

  Autor

Participantes de fora da FMUP

• Moreira, HR
• Rodrigues, DB
• Freitas-Ribeiro, S
• da Silva, LP
• Morais, AD
• Jarnalo, M
• Reis, RL
• Pirraco, RP
• Marques, AP

Unidades de investigação

• Cirurgia e Fisiologia

Abstract

Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that alpha v beta 3 integrin-specific 3D matrices were able to retain PECAM1(+) cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that alpha v beta 3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized alpha v beta 3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability.

Keywords

• Cell signaling; Chemical activation; Tissue; biomaterial; caspase 8; growth factor; hydrogel; paxillin; vitronectin receptor; Cell migration; Cell survival; Endothelial-cells; Engineered materials; Growth factor; In-vivo; Integrin binding; Integrins; Neo-vascularization; Vasculogenesis; adipose tissue; angiogenesis; apoptosis; Article; cardiovascular system; cell migration; cell survival; controlled study; endothelium cell; human; human cell; in vitro study; neovascularization (pathology); protein binding; signal transduction; stromal vascular fraction; tissue engineering; Endothelial cells