Engineering vessel-like networks within multicellular fibrin-based constructs

Ayelet Lesman, Jacob Koffler, Roee Atlas, Yaron J. Blinder, Zvi Kam, Shulamit Levenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Sufficient vascularization in engineered tissues can be achieved through coordinated application of improved biomaterial systems with proper cell types. In this study, we employed 3D fibrin gels alone or in combination with the synthetic poly(l-lactic acid) (PLLA)/polylactic-glycolic acid (PLGA) sponges to support in-vitro construct vascularization and to enhance neovascularization upon implantation. Two multicellular assays were embedded in these constructs: (a) co-culture of endothelial (EC) and fibroblast cells, and (b) a tri-culture combination of ECs, fibroblasts and tissue specific skeletal myoblast cells. In-vitro vessel network formation was examined under advanced confocal microscopy in various time points from cell seeding. Vessel network maturity levels and morphology were found to be highly regulated by fibrinogen concentrations in-vitro. Combination of PLLA/PLGA sponges with fibrin matrices provided added mechanical strength and featured highly mature vessels-like networks. Implantation studies revealed that the implanted ECs developed into 3D interconnected vessel-like networks in-vivo. The PLLA/PLGA scaffold proved to be a key stimulator of neovascularization and perfusion of implanted grafts. Our findings demonstrate that complex biomaterial platform involving fibrin and PLLA/PLGA synthetic scaffold provide a way to enhancing vascularization in-vitro and in-vivo.

Original languageEnglish
Pages (from-to)7856-7869
Number of pages14
Issue number31
StatePublished - Nov 2011
Externally publishedYes


FundersFunder number
Israeli Ministry of Industry & Trade
Omrix Biopharmaceuticals Ltd


    • Angiogenesis
    • Cell encapsulation
    • Co-culture
    • Endothelial cell
    • Fibrin
    • Scaffold


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