Tissue engineering holds enormous potential to replace or restore the function of damaged tissues. Nevertheless, functional vascular network must be generated to deliver blood quickly upon implantation. The invention is based on the clinically approved Fibrin gel (BAC2 and Thrombin) in a novel tissue engineering method. Specifically, two different methods are developed for the construction of a 3-dimentional vascularized tissue:
1) A 3-dimentional Fibrin gel as a cell encapsulating material in combination with vascular cells (endothelial and fibroblast cells) and tissue specific cells for the formation of a tissue engineered construct with internal blood vessel architecture.
2) A 3-dimentional hybrid construct made of PLLA/PLGA sponge scaffold and Fibrin gel. Vascular cells (endothelial and fibroblast cells) and tissue specific cells are co-seeded together with the Fibrin gel on the polymeric sponge to form a tissue-engineered construct with internal blood vessel architecture.
Formation of 3D vessel-like networks in-vivo. (A, B) HUVEC-expressing RFP (red) following 10 days of implantation in-vivo. FITC-Dextran (green) was injected to identify functional host- and human-derived vessels. (C) HUVEC-RFP cells co-implanted with HFF cells within fibrin-based constructs formed 3D interconnected vessel-like network arrays in-vivo. (D-F) Close physical interactions between vessels lined by implanted HUVEC-RFP cells and host neovessels penetrating the graft area were noticed.
- Fibrin gel allows minimizing cells lost during the seeding procedure.
- Biological cross-talk with cells and stimulation of angiogenesis in-vivo.
- Allows to control the mechanical and native environment and micro-environment
Applications and Opportunities
- Supporting 3-dimentional matrix for the formation of various engineered tissues in-vitro as well for the integration of vascular network within the engineered tissue of choice conditions
- Fibrin matrix as a cell carrier for direct injection of cells