Abstract
Angiogenesis, the formation of new blood vessels by sprouting from pre-existing ones, is critical for the establishment and maintenance of complex tissues. Angiogenesis is usually triggered by soluble growth factors such as VEGF. However, geometrical cues also play an important role in this process. Here we report the induction of angiogenesis solely by SVVYGLR peptide micropatterning on polymer surfaces. SVVYGLR peptide stripes were micropatterned onto polymer surfaces by photolithography to study their effects on endothelial cell (EC) behavior. Our results showed that the EC behaviors (cell spreading, orientation and migration) were significantly more guided and regulated on narrower SVVYGLR micropatterns (10 and 50 µm) than on larger stripes (100 µm). Also, EC morphogenesis into tube formation was switched on onto the smaller patterns. We illustrated that the central lumen of tubular structures can be formed by only one-to-four cells due to geometrical constraints on the micropatterns which mediated cell-substrate adhesion and generated a correct maturation of adherens junctions. In addition, sprouting of ECs and vascular networks were also induced by geometrical cues on surfaces micropatterned with SVVYGLR peptides. These micropatterned surfaces provide opportunities for mimicking angiogenesis by peptide modification instead of exogenous growth factors. The organization of ECs into tubular structures and the induction of sprouting angiogenesis are important towards the fabrication of vascularized tissues, and this work has great potential applications in tissue engineering and tissue regeneration.
Highlights
Angiogenesis, the formation of new blood vessels by a process of sprouting from pre-existing ones [1], plays an important role in both normal developmental processes and numerous pathologies, ranging from tumor growth and metastasis to inflammation and ocular diseases [2]
It has been shown that endothelial cell (EC) morphogenesis can be regulated and guided by micropatterning of SVVYGLR peptides depending on the geometrical cues
EC behaviors were significantly more regulated on narrow SVVYGLR micropatterns, ECs were restrictedly spread and the cell orientation and migration were directionally regulated on narrower patterns (10 and 50 mm) as compared with larger stripes (100 mm), resulting in EC morphogenesis into tube formation on the smaller patterns
Summary
Angiogenesis, the formation of new blood vessels by a process of sprouting from pre-existing ones [1], plays an important role in both normal developmental processes and numerous pathologies, ranging from tumor growth and metastasis to inflammation and ocular diseases [2]. It is critical for the establishment and maintenance of large engineered tissues, and as known, vascularization is a critical challenge in tissue engineering [3]. Numerous inducers of angiogenesis have been identified, such as extracellular matrix (ECM) proteins (laminin, collagen, etc) [9] and growth factors (VEGF, bFGF, etc) [5,10]
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