Biomaterials play an important role in most tissue engineering strategies. They can serve as substrates on which cell populations can attach and migrate, can be used as cell delivery vehicles and as bioactive factor carriers to activate specific cellular functions. A series of biodegradable polyurethanes (PUs) with tunable chemical, physical and degradation properties, showing an adequate response to in vitro tests was proposed for applications in soft tissue engineering. Three-dimensional scaffolds of superimposed square meshed grids were prepared by using a rapid prototyping technique (pressure activated microsyringe, PAM) and tested in vivo. Functionalization of PU systems was performed in order to control the chemistry of the materials for the promotion of highly specific binding interactions between materials and biological environments. Two different approaches were used for the coupling of bioactive molecules such as gelatin. The first involved the modification of the polymer chain through a novel monomer and the second one consisted in a surface modification by plasma-induced graft copolymerization of acrylic acid. Copyright © 2006 John Wiley & Sons, Ltd.