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Modified fibrin hydrogel matrices: both, 3D-scaffolds and local and controlled release systems to stimulate angiogenesis.

Sufficient blood perfusion is essential for all tissues to guarantee nutrient- and gas exchange. As many diseases are induced by the reduction of blood perfusion such that these tissues gradually loose their ability to function properly, therapeutic angiogenesis aims to increase blood flow in ischemic tissues by stimulating the patient's endogenous capacity to develop new blood vessels. These studies include application of angiogenesis stimulating (growth) factors and adhesion sequences as well as local gene therapy. One approach is to rationally design 3D-fibrin hydrogel matrices that provide specific adhesion sequences such as a receptor for alpha v beta 3-integrin expressed on angiogenic endothelial cells and that, in addition, are able to store and release angiogenic growth factors such as VEGF-A(165) and bFGF that target cell type-specific responses. Moreover, these matrices can be modified to release complexed plasmid DNA that transfect surrounding cells and improve angiogenesis. During wound healing, cells infiltrate into the scaffold and degrade it, thereby releasing entrapped growth factors or complexed plasmid DNA, and with the speed of tissue regeneration the scaffold is completely removed when tissue healing is achieved. The long-term aim is to develop biomimetic 3D-matrices for applications in a biomaterials context that can be applied directly at the site of injury by minimal invasive surgery. 3D-fibrin matrices constitute a scaffold and release system for single or combined therapeutic biomolecules and may therefore be able to contribute to the patients' endogenous healing response resulting in the functional recovery of a diseased tissue or organ.