Synthesis and characterization of biodegradable elastomeric polyurethane scaffolds fabricated by the inkjet technique Changhong Zhang, Xuejun Wen, Naren R. Vyavahare, Thomas Boland * Department of Bioengineering, Clemson University, 420 Rhodes Research Centre, Clemson, SC 29634, USA article info Article history: Received 15 February 2008 Accepted 7 June 2008 Available online 3 July 2008 Keywords: Biodegradation Cell adhesion Cell proliferation Cell–material interaction Degradation Mechanical properties abstract Biodegradable polyurethanes (PUs) were synthesized from methylene di-p-phenyl-diisocyanate (MDI), polycaprolactone diol (PCL-diol) and N,N-bis (2-hydorxyethyl)-2-aminoethane-sulfonic acid (BES), serving as a hard segment, soft segment and chain extender, respectively. MDI was chosen due to its reactivity and wide application in synthesis of biomedical polyurethanes due to its reactivity; PCL-diol was chosen because of its biodegradability; and BES was chosen because it allowed the introduction sulfonic acid groups onto the polymer chains. We evaluated the polyurethanes’ degradation rate, me- chanical properties, hydrophilicity, antithrombogenecity, and ability to support fibroblast cell attachment and growth by comparing with polymers having a 2,2-(methylimino)diethanol (MIDE) chain extender. Mechanical testing demonstrated that the PU containing BES has tensile strengths of about 17 MPa and elongations up to 400%, about three times the strength and four times the elongation than the MIDE based PUs. The polymers showed decreased in vitro degradation rates, lower glass transition temperature (T g ) and hydrophilicity possibly due to enhanced microphase separation. Preliminary cytocompatibility studies showed that all the PUs are non-toxic, but PU containing BES exhibited much lower cell at- tachment and proliferation than the MIDE chain extended polymers. An in vitro platelet adhesion assay showed lower platelet attachment on BES containing PU. Additionally, due to the existence of sulfonic acid groups, the BES extended PU became water soluble in basic condition and insoluble in acidic condition, a phenomenon that is reversible at pH value of 8.7, making this a pH sensitive polymer at- tractive for bioprinting applications. By adding acetic acid into an inkjet cartridge and printing it onto a PU solution with pH above 8.7, precision fabricated scaffolds can be obtained, suggesting that BES based PUs are promising candidates as synthetic inks used for customizable fabrication of tissue engineering scaffolds. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction For decades, polyurethanes (PUs) have been a biomaterial of choice for many applications [1,2] because of their biocompatibility and excellent mechanical properties. However, as most poly- urethanes are non-degradable, they may cause long-term foreign body reaction, may fail to integrate or exhibit material fatigue and have found little use in the field of tissue engineering [3]. Degradable biomaterials, on the other hand, whether natural or synthetic, have poor mechanical properties; the majorities are either too stiff with low flexibility or too soft with relatively low strength [4–6]. To overcome those limitations, a number of degradable PUs have been introduced for a range of biomedical applications varying from cardiovascular repair, cartilage implant, ligament regeneration, bone replacement to controlled drug/gene delivery [7–9]. It has been shown that incorporation of sulfonic groups into non-degradable PUs will improve the polymers’ blood compati- bility, an effect explained by principle that the electrostatic re- pulsion between the sulfonic groups and the blood proteins lessens protein adsorption and lowers platelet adhesion and activation [10,11]. Several studies found that the incorporation of sulfonic groups also affected other physical properties, such as the glass transition, tensile strength, modulus, melt viscosity, relaxation behavior, and solution behavior. Generally, these polymers show a higher degree of water absorption than their non-sulfonated counterparts [12], and exhibit reduced mechanical properties in aqueous solutions due to their water absorption. Some researchers found that the increased sulfonic ion content in the PU backbone resulted in the water soluble polymers; other groups reported that the sulfonated PUs became water soluble in basic environment but water insoluble in acidic environment [13,14]. However, there are no reports about how to utilize these pH sensitive polymers to fabricate scaffolds. Furthermore, although much research work has been done incorporating sulfonic groups into non-degradable PUs, * Corresponding author. Tel.: þ1 864 656 7639; fax: þ1 864 656 4466. E-mail address: tboland@clemson.edu (T. Boland). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.06.009 Biomaterials 29 (2008) 3781–3791