Carbohydrate Polymers 87 (2012) 926–929 Contents lists available at ScienceDirect Carbohydrate Polymers j ourna l ho me pag e: www.elsevier.com/locate/carbpol Short communication Electrospinning of hyaluronic acid nanofibers from aqueous ammonium solutions Eric K. Brenner, Jessica D. Schiffman, Ebony A. Thompson, Laura J. Toth, Caroline L. Schauer ∗ Department of Materials Science and Engineering, Drexel University, Philadelphia, PA 19104, United States a r t i c l e i n f o Article history: Received 2 March 2011 Received in revised form 20 July 2011 Accepted 21 July 2011 Available online 28 July 2011 Keywords: Biopolymer Electrospinning Fibers Nanofiber Hyaluronic acid a b s t r a c t For several reasons, the electrospinning of nanofibrous mats comprised purely of biopolymers, such as hyaluronic acid (HA) has been difficult to achieve. Most notably, due to its polyelectrolytic nature, very low polymer concentrations exhibit very high solution viscosities. Thus, it is challenging to obtain the critical chain entanglement concentration necessary for biopolymer electrospinning to ensue. While the successful electrospinning of HA fibers from a sodium hydroxide:dimethylformamide (NaOH:DMF) system has been reported, the diameter of these fibers was well above 100 nm. Moreover, questions regarding the degradation of HA within the solvent system arose. These factors supported our ongoing research into determining an improved solvent system. In this study, the use of a less basic (pH 11) aqueous ammonium hydroxide (NH 4 OH) solvent system, NH 4 OH:DMF, allowed for the fabrication of HA mats having an average fiber diameter of 39 ± 12 nm. Importantly, while using this solvent system, no degradation effects were observed and the continuous electrospinning of pure HA fibers was possible. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Hyaluronic acid (HA) is a major glycosaminoglycan found in the extracellular matrix of many soft tissues in higher ani- mals. It is a linear natural polysaccharide composed of repeating disaccharide units of -1-4-d-glucuronic acid and -1-3-N-acetyl- d-glucosamine. The complete biocompatibility of HA has led to extensive research into its use in biomedical applications, includ- ing, ophthalmology, drug delivery, dermatology, tissue scaffolding, and medical implants (Huskisson & Donnelly, 1999; Jia & Kiick, 2009; Kim, Chung, & Park, 2008; Nesti et al., 2008; Yoo, Lee, Yoon, & Park, 2005). Numerous tissue engineering applications – substrates for tis- sue regeneration, wound dressing scaffolds, and artificial blood vessels – would benefit from the increased surface area-to-volume ratios and range of pore sizes that electrospun nanofibrous mats have to offer. Electrospinning is a simple and inexpensive method for producing nanoscale non-woven polymer mats which exhibit these desirable intrinsic structure–property relationships. It is for this reason that the production of pure biopolymer nanofibrous mats has been of renewed interest in recent years (Schiffman & Schauer, 2008). However, complications arise when working with charged biopolymer solutions due to their long-range electrostatic inter- actions and the presence of counter ions (Schiffman & Schauer, ∗ Corresponding author. Tel.: +1 2158956797; fax: +1 2158956760. E-mail address: cschauer@coe.drexel.edu (C.L. Schauer). 2008). As a result of these interactions, HA forms highly viscous solutions at low polymer concentrations, which severely hinders its electrospinnability. Reaching the critical chain entanglement concentration is one requirement for fiber formation as it ensures that a critical amount of polymer chains will overlap and topologi- cally constrain each other’s motion (McKee, Wilkes, Colby, & Long, 2004). To reach this critical point before the onset of high solution viscosity, literature has previously blended HA with uncharged car- rier polymers including collagen (Hsu, Hung, Liou, & Shen, 2010), gelatin (Li, He, Han, et al., 2006; Li, He, Zheng, & Han, 2006), and zein (Yao, Li, & Song, 2007). Poly(ethylene oxide) (PEO) was mixed with a thiolated HA derivative, 3,3 ′ -dithiobis(propanoic dihydrazide) (HA- DTPH) to create crosslinked nanofibrous mats (Ji, Ghosh, Li, et al., 2006; Ji, Ghosh, Shu, et al., 2006). To overcome the issue of high solution viscosity and electrospin HA without a carrier polymer, Um et al. (Um, Fang, Hsiao, Okamoto, & Chu, 2004), have demon- strated the use of an altered electrospinning setup, which featured air assisted blowing and elevated temperatures. Electrospinning of pure HA dissolved in dimethylformamide (DMF):water (H 2 O) (Li, He, Han, et al., 2006) solutions has been demonstrated with the aid of elevated temperatures and an ethanol coagulation bath. Recently, a tri-component by weight system fea- turing 25:50:25 H 2 O:formic acid (FA):DMF was reported by Liu et al. (2011). However, since the pH of this solution is approx- imately 2–3, the protonation of the HA carboxylate can change the properties of the biopolyelectrolyte thus reducing the charged groups. A third system featuring sodium hydroxide (NaOH) and DMF (Kim, Chung, & Park, 2008) has also been reported in the liter- ature. At the time of our work, the H 2 O:FA:DMF system was not yet 0144-8617/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbpol.2011.07.033