Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol A terpolymeric hydrogel of hyaluronate-hydroxyethyl acrylate-gelatin methacryloyl with tunable properties as biomaterial Dipankar Das a,b , Hana Cho c , Nahye Kim b , Thi Thu Hien Pham b , In Gul Kim c , Eun-Jae Chung c , Insup Noh a,b, ⁎ a Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea b Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea c Department of Otorhinolaryngology, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea ARTICLEINFO Keywords: Bovine serum albumin Dexamethasone Drug delivery Human chondrocytes Hyaluronate Hydrogel ABSTRACT Here, we report synthesis of a terpolymeric covalently crosslinked hydrogel of hyaluronate (HA) as biomaterial with elasticity, mechanical properties and cell interactions via conventional free radical polymerization tech- nique. To provide elasticity and mechanical properties, 2-hydroxyethyl acrylate (HEA) was grafted in HA, while to tune cellular interactions, gelatin methacryloyl (GM) was used as crosslinker. The composition and probable structure of the terpolymer (HA-g-pHEA-x-GM) were analysed by FTIR, 1 H HR-MAS-NMR, and TGA analyses. The SEM and texture analyses of hydrogel showed interconnected micro-porous network and high mechanical properties, respectively. In vitro biocompatibility was studied against human chondrocytes, whereas, in vivo biocompatibility and tissue regeneration were confrmed using mouse model. The hydrogel releases model protein-bovine serum albumin, and corticosteroid drug-dexamethasone in a sustain way at pH 7.4 and 37°C. Overall, the tunable mechanical properties, micro-porous network, and cytocompatibility of the HA-g-pHEA-x- GM hydrogel highlights its potential applicability in cartilage tissue engineering and drug delivery. 1. Introduction During the past few decades, the design and development of new hydrogel-based biomaterials with tunable physical, mechanical, and biological characteristics are enormously growing for the progress of biomedical science and industrial applications (Das, Ghosh, Dhara, Panda, & Pal, 2015; Das, Ghosh, Ghosh et al., 2015; Fares et al., 2018; Gopinathan & Noh, 2018; Park, Lee, An, & Lee, 2017). Hydrogels are three-dimensional, hydrophilic, physically or chemically crosslinked polymer networks which swell by absorbing water or biological fuids while preserving their physicochemical integrity (Das & Pal, 2015; Varnier et al., 2018). Natural polysaccharides have extensively been used to design hydrogels for biomedical applications because of their biocompatibility, non-toxicity, biodegradability, water solubility, and presenceofvariousfunctionalgroups(e.g.,−OH, eNH 2 ,COOH etc.)for modifcation (Das & Pal, 2015; Varnier et al., 2018). The water soluble nature of the individual polysaccharide and poor mechanical strength of physically crosslinked hydrogel have been improved through che- mical crosslinking method which resulted in the formation of chemi- cally crosslinked hydrogel, contains covalent bond as well as physical interactions (hydrogen or ionic bonds) between the polymeric units (Das & Pal, 2015; Guilherme et al., 2015; Varnier et al., 2018). Among naturally derived polymers, hyaluronic acid (HA) gained signifcant attention in the preparation of hydrogels for biomedical applications (An et al., 2018; Das, Pham, & Noh, 2018). Hyaluronic acid is a poly- saccharide of D-glucuronic acid and N-acetyl-D-glucosamine (Das, Pham et al., 2018; Larraneta et al., 2018; Ouasti et al., 2011; Roig, Blanzat, Solans, Esquena, & Garcia-Celma, 2018). It is found in skin (Mero & Campisi, 2014), pericellular, extracellular, and intracellular tissues of the body (Collins & Birkinshaw, 2013; Larraneta et al., 2018; Ouasti et al., 2011). It participates in biological activities, like cell growth, migration and dif ;erentiation (Hemshekhar et al., 2016). HA is hy- drophilic, non-immunogenic, biocompatible, and degraded by hyalur- onidases (Highley, Prestwich, & Burdick, 2016; Tripodo et al., 2015). Becauseofthesebiocompatiblefeatures,HAbasedhydrogelshavebeen employed in tissue engineering (Chen et al., 2017; Collins & Birkinshaw, 2013; Cui, Qian, Liu, Zhao, & Wang, 2015; Das, Pham et al., 2018; Hemshekhar et al., 2016; Mahapatra, Jin, & Kim, 2016; Yeom, Hwang, Yang, Shin, & Hahn, 2014; Yu et al., 2014), to drug delivery (Das, Pham et al., 2018; Fiorica, Palumbo, Pitarresi, Bongiovi, https://doi.org/10.1016/j.carbpol.2018.12.020 Received 6 October 2018; Received in revised form 29 November 2018; Accepted 10 December 2018 ⁎ Correspondingauthorat:DepartmentofChemicalandBiomolecularEngineering,SeoulNationalUniversityofScienceandTechnology,Seoul,01811,Republicof Korea. E-mail address: insup@seoultech.ac.kr (I. Noh). Carbohydrate Polymers 207 (2019) 628–639 Available online 11 December 2018 0144-8617/ © 2018 Elsevier Ltd. All rights reserved. T