Flexible and elastic porous poly(trimethylene carbonate) structures for use in vascular tissue engineering Y. Song a , M.M.J. Kamphuis a,b , Z. Zhang a , L.M.Th. Sterk c , I. Vermes a,b , A.A. Poot a , J. Feijen a , D.W. Grijpma a,d, * a Institute for Biomedical Technology (BMTI) and Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands b Department of Clinical Chemistry, Medical Spectrum Twente Hospital, PO Box 50000, 7500 KA Enschede, The Netherlands c Laboratory for Pathology, PO Box 377, 7500 AJ Enschede, The Netherlands d Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands article info Article history: Received 31 March 2009 Received in revised form 24 September 2009 Accepted 1 October 2009 Available online 7 October 2009 Keywords: Tissue engineering Blood vessels Tubular scaffolds Cross-linked PTMC abstract Biocompatible and elastic porous tubular structures based on poly(1,3-trimethylene carbonate), PTMC, were developed as scaffolds for tissue engineering of small-diameter blood vessels. High-molecular- weight PTMC (M n = 4.37  10 5 ) was cross-linked by gamma-irradiation in an inert nitrogen atmosphere. The resulting networks (50–70% gel content) were elastic and creep resistant. The PTMC materials were highly biocompatible as determined by cell adhesion and proliferation studies using various relevant cell types (human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs) and mesenchymal stem cells (MSCs)). Dimensionally stable tubular scaffolds with an interconnected pore network were prepared by particulate leaching. Different cross-linked porous PTMC specimens with average pore sizes ranging between 55 and 116 lm, and porosities ranging from 59% to 83% were prepared. These scaffolds were highly compliant and flexible, with high elongations at break. Furthermore, their resistance to creep was excellent and under cyclic loading conditions (20 deformation cycles to 30% elongation) no perma- nent deformation occurred. Seeding of SMCs into the wall of the tubular structures was done by carefully perfusing cell suspensions with syringes from the lumen through the wall. The cells were then cultured for 7 days. Upon proliferation of the SMCs, the formed blood vessel constructs had excellent mechanical properties. Their radial tensile strengths had increased from 0.23 to 0.78 MPa, which is close to those of natural blood vessels. Ó 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Diseased coronary arteries and peripheral blood vessels often require replacement with small-diameter grafts. Autologous arter- ies or veins are the best substitutes, but approximately one-third of the patients do not have suitable veins for grafting [1,2]. Due to the occurrence of thrombogenesis and intimal hyperplasia [3], it is not yet possible to use synthetic vascular grafts with inner diameters smaller than 6 mm [4,5]. In tissue engineering of small-diameter blood vessels, grafts can be constructed in a bioreactor using tubular scaffolds, cells and growth factors [6]. The scaffolding material should allow cell adhesion and proliferation and have adequate mechanical properties. To allow mechanical stimulation of the cells during culturing in vitro, the scaffold should be sufficiently strong, flexible and elas- tic. The cell–scaffold constructs should resist physiological blood pressures, and recover from the repeated dilations during the rel- atively long culturing times [7,8]. Preferably the scaffold should degrade, but the mechanical properties of the construct should re- main at an acceptable level, implying that the newly formed tissue will compensate for degradation of the scaffold. Natural polymeric materials have been used in preparing such scaffolding structures. Tubular constructs that mimic the native structure of an artery have been prepared by incorporating smooth muscle cells (SMCs) in collagen and elastin matrices [6]. Swartz et al. have engineered blood vessels with an inner diameter of 4 mm entirely from fibrin as a scaffolding material. In vivo, these grafts remained patent for approximately 15 weeks [9]. Unfortu- nately, as a result of their limited mechanical strength, these scaf- folds needed to be supported initially, and could not be used in the culturing of cells under dynamic flow conditions. Decellularized (human) blood arteries, which are only composed of extra-cellular matrix, have suitable mechanical properties [10,11], but the 1742-7061/$ - see front matter Ó 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.actbio.2009.10.002 * Corresponding author. Address: Institute for Biomedical Technology (BMTI) and Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands. Tel.: +31 53 4892966; fax: +31 53 4892155. E-mail address: d.w.grijpma@tnw.utwente.nl (D.W. Grijpma). Acta Biomaterialia 6 (2010) 1269–1277 Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat