Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro

• Published in: Biomaterials 2005-04, Vol.26 (12), p.1369-1379
• Main Authors: Urech, Lukas, Bittermann, Anne Greet, Hubbell, Jeffrey.A., Hall, Heike
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Angiogenesis; Biocompatible Materials - chemistry; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Elasticity; Endothelial cell; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Fibrin; Fibrin - chemistry; Fibrin - ultrastructure; Humans; Hydrogels; Materials Testing; Matrix metalloproteinases; Mechanical properties; Molecular Weight; Neovascularization, Physiologic - physiology; Neural Cell Adhesion Molecule L1 - chemistry; Neural Cell Adhesion Molecule L1 - pharmacology; Neural Cell Adhesion Molecule L1 - ultrastructure; Surface Properties; Tissue Engineering - methods
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2004.04.045

During initial stages of wound healing, fibrin clots provide a three-dimensional scaffold that induces cell infiltration and regeneration. Here, L1Ig6, a ligand for αv β3 integrin was covalently incorporated within fibrin matrices to explore it as a matrix-immobilized angiogenic factor. Incorporation at concentrations greater than 1 μg/ml reduced the fibrin crosslink density, as reflected by measurements of elastic modulus and swelling. The influence of crosslink density on endothelial cell process extension was characterized by modulating factor XIII concentrations in the coagulation mixture. At low incorporated concentrations of L1Ig6, it was possible to compensate gel elastic modulus via increased factor XIII, but not at high concentrations of L1Ig6. Similar findings were found when matrix swelling was analyzed. Fibrin crosslink density strongly influenced endothelial cell process extension, fewer and shorter processes were observed at high crosslink density. Matrix metalloproteinases (MMPs) were required for process extension and zymography and Western blots identified MMP-2 but not MMP-9. The amount of active MMP-2 increased for endothelial cells cultured in native and L1Ig6-modified matrices or when stimulated with VEGF-A 165. The data indicate that distinct matrix properties can be tailored such that they become biologically stimulating and respond to cellular proteolytic activities, being a prerequisite for potential use of such matrices in biomedical applications.