Degradable block polyurethanes from nontoxic building blocks as scaffold materials to support cell growth and proliferation A. Rechichi, 1 G. Ciardelli, 2 M. D’Acunto, 3 G. Vozzi, 1 P. Giusti 1,3 1 National Research Council-Institute for Composite and Biomedical Materials, via Diotisalvi 2, 56126 Pisa, Italy 2 Department of Mechanics, Politecnico in Turin, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy 3 Department of Chemical Engineering, University of Pisa, via Diotisalvi 2, 56126 Pisa, Italy Received 13 March 2006; revised 25 January 2007; accepted 31 January 2007 Published online 17 July 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.31349 Abstract: Linear degradable polyurethanes were prepared and proposed for tissue engineering applications. Biocompat- ible segments were selected for the synthesis to promote their integration with the biological environment. Physicochemical and morphological characterization (SEC, DSC, DMTA, AFM) revealed that the properties of these polymeric systems can be easily tuned by varying the nature and the composi- tion of the constituent segments. In vitro biological assays (citotoxicity, fibroblast adhesion, and proliferation) showed that all polymers are not toxic, promoting the adhesion and proliferation of fibroblast cells, with slight differences depending on the material hydrophilicity. Ó 2007 Wiley Peri- odicals, Inc. J Biomed Mater Res 84A: 847–855, 2008 Key words: polyurethanes; tissue engineering; atomic force microscopy; cell adhesion; in vitro test INTRODUCTION Polyurethanes represent a main class of synthetic elastomers applied for long-term medical implants. 1–3 They present tuneable chemical properties, excellent mechanical properties, good blood compatibility, and can be designed to degrade in biological environ- ments. 4 The main problem in their use as biodegradable materials in biomedical field is due to the possible release of toxic diamines when conventional isocya- nates are used in their synthesis. 5 To overcome this problem, aliphatic diisocyanates such as an L-lysine derived diisocyanate (LDI) 6 and 1,4-diisocyanatobu- tane 7 were applied in the synthesis of polyurethanes for tissue engineering applications. Bruin et al. 8 realized PU networks using star-shaped polyester prepolymers reacted with LDI. However the high cross-linking degree inhibited the use of the process standard techniques. Hirt et al. studied 9,10 the syn- thesis, characterization, and degradation of linear polyurethanes prepared from LDI and a series of polyester macrodiols (having poly-3-(R)-hydroxybu- tyrate as the hard segment and glycolide and e-capro- lactone copolymers as the soft segments). In vitro studies showed that these materials were biocompati- ble, did not activate macrophages and gave good level of cell adhesion when processed in the form of porous scaffolds. These results were confirmed in vivo. 11 Subsequent work of Zang et al. 12 involved the preparation of cross-linked polyurethanes based on LDI and glycerol in the form of sponges as scaf- folds for tissue engineering. In vivo preliminary stud- ies showed that structures supported cell growth. Polyurethane based microporous scaffolds were also designed for meniscus regeneration by Spaans et al. 13 More recently Skarja and Woodhouse 14,15 proposed a series of L-phenylalanine based diamine (amino-phe- nyl-acetic acid 4-(2-amino-2-phenyl-acetoxymethyl)- cyclohexylmethyl ester, Phe diester) containing poly- urethane-ureas with tuneable degradation properties for soft tissue repair applications. In a recent work 16 we proposed the synthesis, char- acterization, and degradation of novel linear polyur- ethanes. The polymers were obtained using LDI as diisocyanate, a cyclic diol (1,4-cyclohexane dime- thanol, CDM) and Phe diester as chain extender, and poly(e-caprolactone) diol (PCL diol) or tri-block copolymers based on polyethylenglycol (PEG) and poly(e-caprolactone) (PCL) as macrodiols. Introduc- tion of such tri-block PCL-PEG-PCL copolymers, prepared according to a procedure involving a bulk Correspondence to: A. Rechichi; e-mail: alfonsina.rechichi@ ing.unipi.it Contract grant sponsor: Italian Ministry of University and Research; contract grant number: FIRB RBNE017RCN ' 2007 Wiley Periodicals, Inc.