Fabrication and characterization of poly-(ε)-caprolactone and bioactive glass composites for tissue engineering applications Ali Mohammadkhah a,1 , Laura M. Marquardt b,1 , Shelly E. Sakiyama-Elbert b , Delbert E. Day a , Amy B. Harkins c, ⁎ a Graduate Center for Materials Research and Center for Biomedical Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409, USA b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA c Department of Pharmacological and Physiological Science, Department of Biomedical Engineering, Saint Louis University, St. Louis, MO 63104, USA abstract article info Article history: Received 1 October 2014 Received in revised form 20 December 2014 Accepted 14 January 2015 Available online 16 January 2015 Keywords: Borate glass Neurite extension Mechanical properties Degradation rate Polymer sheet Much work has focused on developing synthetic materials that have tailored degradation profiles and physical properties that may prove useful in developing biomaterials for tissue engineering applications. In the present study, three different composite sheets consisting of biodegradable poly-ε-caprolactone (PCL) and varying types of bioactive glass were investigated. The three composites were composed of 50 wt.% PCL and (1) 50 wt.% 13–93 B3 borate glass particles, (2) 50 wt.% 45S5 silicate glass particles, or (3) a blend of 25 wt.% 13–93 B3 and 25 wt.% 45S5 glass particles. Degradation profiles determined for each composite showed the com- posite that contained only 13–93 B3 borate glass had a higher degradation rate compared to the composite con- taining only 45S5 silicate glass. Uniaxial tensile tests were performed on the composites to determine the effect of adding glass to the polymer on mechanical properties. The peak stress of all of the composites was lower than that of PCL alone, but 100% PCL had a higher stiffness when pre-reacted in cell media for 6 weeks, whereas com- posite sheets did not. Finally, to determine whether the composite sheets would maintain neuronal growth, dor- sal root ganglia isolated from embryonic chicks were cultured on composite sheets, and neurite outgrowth was measured. The bioactive glass particles added to the composites showed no negative effects on neurite extension, and neurite extension increased on PCL:45S5 PCL:13–93 B3 when pre-reacted in media for 24 h. This work shows that composite sheets of PCL and bioactive glass particles provide a flexible biomaterial for neural tissue engi- neering applications. © 2015 Elsevier B.V. All rights reserved. 1. Introduction Ideal nerve repair biomaterials should be biocompatible and non- inflammatory, yet flexible with adequate tensile strength to prevent nerve compression [1]. The materials should be biodegradable with a porosity and permeability to supply adequate oxygen and nutrients [1]. Nerve autografts remain the gold standard in nerve repair and re- generation because of their performance. However, autografts require additional surgery, may cause donor site morbidity, and the loss of nerve function; all reasons that alternative materials in nerve repair and regeneration are needed. Bioresorbable synthetic natural polymers such as type I collagen (for example Neuragen®) have received attention over the last decade due to ease of production and controlled degradation. Type I collagen supports glial cell attachment, proliferation, unidirectional neurite ex- tension, and axonal regeneration in vivo [2–6]. The disadvantages to using natural polymers for nerve conduits include poor mechanical properties and batch-to-batch variability [7–9]. Resorbable synthetic polymers have been used extensively to repair peripheral nerves due to lower cost, simple fabrication, and proven efficacy [1]. Compared to an autograft, these synthetic materials eliminate the shortcomings of the autograft [1]. Because of their biodegradability, poly-ε-caprolactone (PCL) and its copolymers have been used for soft tissue regeneration ap- plications [10] including peripheral nerves [11–14]. PCL slowly de- grades in vivo and its degradation can take several years depending upon its molecular weight [15]. Furthermore, the degradation rate of PCL can be altered by polymerization with other polymers such as poly-lactic acid (PLA) [15]. Addition of inorganic materials such as bioactive glass to a biode- gradable polymer improves the mechanical strength [10] and enhances the wetting properties of certain polymers [16–18], which can improve cell adhesion [16–19]. Lei et al. have shown that by adding 30 wt.% bio- active glass microspheres to PCL films, the elastic modulus increases by ~6 times and the contact angle decreases by ~50% compared to 100% PCL films [17,18]. Pre-osteoblast MC3T3-E1 cells were shown to spread more uniformly on a PCL/bioactive glass (BG) composite compared to a pure PCL film [17,18]. BGs are effective in biomedical applications that include bone repair [20] and peripheral nerve repair [21]. For example, Jeans et al. used a rigid glass tube made from a sodium calcium Materials Science and Engineering C 49 (2015) 632–639 ⁎ Corresponding author at: Department of Pharmacological and Physiological Science, 1402 S. Grand Blvd., Saint Louis University, St. Louis, MO 63104, USA. E-mail address: harkinsa@slu.edu (A.B. Harkins). 1 Equal first authorship. http://dx.doi.org/10.1016/j.msec.2015.01.060 0928-4931/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec