New poly(ester urea) derived from L-leucine: Electrospun scaffolds loaded with antibacterial drugs and enzymes Angélica Díaz a , Luis J. del Valle a , David Tugushi b , Ramaz Katsarava b , Jordi Puiggalí a, ⁎ a Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028, Spain b Institute of Chemistry and Molecular Engineering, Agricultural University of Georgia, 13 km. David Aghmashenebeli Alley, Tblisi 0131, Georgia abstract article info Article history: Received 28 June 2014 Received in revised form 18 September 2014 Accepted 21 October 2014 Available online 23 October 2014 Keywords: Poly(ester urea) L-Leucine Electrospinning Scaffold Enzymatic degradation Biocompatibility Biguanide Drug release Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising mate- rials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol- diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibro- blast and epithelial cells. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Poly(ester urea)s (PEUs) have been proposed as a new class of α- amino acid-based polymers with bioabsorbable properties. These poly- mers can be easily prepared from bis(α-amino acid)-alkylene diester monomers, which can undergo either nonspecific (chemical) or specific (enzymatic) hydrolysis due to the presence of two ester linkages per el- emental unit in the molecule. The first syntheses were reported in the late 1970s by Huang et al. [1] and yielded low molecular weight powdery samples (M n close to 2000 g/mol). Later, Yoneyama et al. synthesized high molecular weight PEUs by condensing the above diester–diamine monomers with non-physiological diisocyanates [2]. In order to avoid the use of diisocyanates, other syntheses based on polycondesation processes through active carbonates (e.g. di-p- nitrophenyl carbonate) were investigated [3]. However, presumably in- tramolecular cyclization with hydantoin formation, which represent a chain scission process, led to low molecular weight polymers. Problems were solved when an acid chloride of carbonic acid (phos- gene, diphosgene, triphosgene) was entered into the polycondensation reaction with a di-p-toluenesulfonic acid salt of a bis(α-amino acid)- alkylene diester (Fig. 1a) [4]. In the interfacial polycondensation reac- tion, the nucleophilic amino group was readily revealed by addition of an inorganic base, such as NaOH, NaHCO 3 and Na 2 CO 3 . This method pro- vides high-yield, high-molecular weight PEUs potentially useful for bio- medical applications because of their advantageous mechanical, chemical and biodegradation properties over well-known, chemically similar poly(ester amide)s also derived from α-amino acids [5]. For ex- ample, the PEU derived from carbonic acid, L-leucine, and 1,6- hexanediol (named 1L6, as indicated in Fig. 1a) has tensile strength at yield, elongation at break and Young's modulus of 21 MPa, 114% and 622 MPa, respectively [4]. Its melting temperature is 114 °C and its glass transition temperature is 47 °C. New PEUs were proposed to be useful as implantable surgical devices such as vascular stents and hard tissue replacement implants, and also for delivery of a variety of phar- maceutical and biologically active agents to humans and other mammals. Micro/nanofiber nonwoven scaffolds produced by electrospinning have shown great potential for tissue engineering applications because of their typically high surface area and porosity. Electrospinning is a well-known electrostatic technique that uses a high voltage field to charge the surface of a polymer solution droplet at the end of a capillary Materials Science and Engineering C 46 (2015) 450–462 ⁎ Corresponding author. E-mail address: Jordi.Puiggali@upc.edu (J. Puiggalí). http://dx.doi.org/10.1016/j.msec.2014.10.055 0928-4931/© 2014 Elsevier B.V. All rights reserved. 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