Tailoring the properties of chitosan-poly(acrylic acid) based hydrogels by hydrophobic monomer incorporation Alina Gabriela Rusu a,b , Marcel Ionel Popa a , Constanta Ibanescu a,c , Maricel Danu c , Liliana Verestiuc d,n a Gheorghe Asachi Technical University, Faculty of Chemical Engineering and Environmental Protection, 73 Dimitrie Mangeron Street, 700050 Iasi, Romania b Alexandru Ioan Cuza University, 11 Carol I Blvd, 700506 Iasi, Romania c Petru Poni Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, Romania d Grigore T.Popa University of Medicine and Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi, Romania article info Article history: Received 7 June 2015 Received in revised form 26 August 2015 Accepted 31 October 2015 Available online 2 November 2015 Keywords: Semi-interpenetrated networks Hydrophilic/hydrophobic microdomains pH sensitivity Mechanical properties abstract Ethyl acrylate was included into pH sensitive hydrogels based on N-maleoyl–chitosan and poly(acrylic acid) in the aim to tailor the swelling capacity and to improve the hydrogels mechanical stability. Hy- drogels morphology analysis indicates a macroporous structure with microdomains (hydrophilic/hy- drophobic) that are spreading, while the uniformity is dependent on the content of ethyl acrylate. The hydrogels conserved the pH sensitivity in aqueous solutions; the ethyl acrylate reduced the swelling capacity and modified the absorption mechanism from anomalous to a Fickian one. Viscoelastic char- acteristics, investigated using oscillatory deformation tests, revealed the formation of chemical–physical crosslinked network; ethyl acrylate increased the mechanical stability of hydrogels. & 2015 Elsevier B.V. All rights reserved. 1. Introduction Hydrogels designed to respond to external stimuli (pH, tem- perature, ionic strength, magnetic fields) have received significant attention in medicine, especially as matrices for wound healing and drug delivery [1,2]. Recent studies in tissue engineering have focused on optimizing the hydrogels morphology, mechanical properties and stimuli responsiveness [3]. Various methods have been reported for tailoring the stimuli-responsive properties of polymeric hydrogels, including functionalization of hydrophilic polyssacharides with hydrophobic compounds [4] and the copo- lymerization of hydrophilic monomers with hydrophobic ones [5]. Incorporation of hydrophobic polymers into hydrogels allows embedding of hydrophobic and/or hydrophilic drugs, while the mechanical properties are increasing [6]. Complexes/matrices of natural and synthetic polymers were also proposed in order to improve the biocompatibility and the intrinsec cellular interac- tions[7]. Functionalized chitosan (Cs), such as N-maleoyl–chitosan, has been considered attractive in preparation of hydrogels as such hydrogels simulate the native extracellular matrices [8,9]. Huang et al. [10] reported the preparation of pH-sensitive graft copolymer for drug delivery applications by grafting acrylic acid onto maleoylchitosan. These hydrogels are pH sensitive due to the ex- istence of pendant acidic (–COOH) and basic (unreacted –NH 2 ) moieties. The aim of this study was to investigate the possibility to mod- ulate the properties of pH-sensitive hydrogels based on N-maleoyl chitosan and poly(acrylic acid–co-ethyl acrylate) (NMACs-P(AA-co- EA) through the content of hydrophobic monomer (ethyl acrylate). Ethyl acrylate is a cell friendly monomer at low concentrations (15- 25%) [11]; it could counterbalance the hydrophilic nature of chitosan derivative and acrylic acid and act as sensitive area for adsorption of hydrophobic drugs, useful in skin tissue regeneration. 2. Materials and methods Hydrogels were prepared by free radical polymerization of acrylic acid (AA) and ethyl acrylate (EA) in presence of N-maleoyl chitosan (NCsMA; 46% substitution degree, synthesized using a procedure described in the literature [12]). Briefly, AA and EA (Table 1) were added to 1%wt. NCsMA solution, followed by an initiating system (ammonium persulfate – APS 5 wt% and tetra- methylethylenediamine-TEMED 5 wt%, aqueous solutions). The prepared mixtures were transferred into molds and allowed to react for 2 h, at 70 °C. The obtained hydrogels were washed in distilled water (3 days) and freeze-dried. Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/matlet Materials Letters http://dx.doi.org/10.1016/j.matlet.2015.10.164 0167-577X/& 2015 Elsevier B.V. All rights reserved. n Corresponding author. E-mail address: liliana.verestiuc@bioinginerie.ro (L. Verestiuc). Materials Letters 164 (2016) 320–324