The mechanical properties of native fibrin matrices covalently modified with ligand L11g6 for angiogenic endothelial cells were analyzed. Native fibrin matrices showed increasing mechanical stability when produced with increasing concentrations of exogenous factor XIII. Human umbilical vein endothelial cells (HUVEC) extended processes into those matrices. Process extension depended on biological modifications with a ligand L11g6 for αvβ3-integrin as well as on the mechanical properties of the matrix. Results show that the HUVEC process extension into three-dimensional fibrin matrices depended on the mechanical properties, the availability of proper adhesion signals and proteolytic degradation on the matrix.