Oxidized dextrins as alternative crosslinking agents for polysaccharides: Application to hydrogels of agarose–chitosan Laura G. Gómez-Mascaraque a,b , José Alberto Méndez c , Mar Fernández-Gutiérrez a,b , Blanca Vázquez a,b,⇑ , Julio San Román a,b a CIBER-BBN, Ebro River Campus, R&D Building, Block 5, Floor 1, Poeta Mariano Esquillor s/n, 50017 Zaragoza, Spain b Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain c Escola Politècnica Superior, Edifici PI, Campus Montilivi, University of Girona, 17071 Girona, Spain article info Article history: Received 29 May 2013 Received in revised form 27 August 2013 Accepted 3 October 2013 Available online xxxx Keywords: Hydrogels Oxidized dextrins Agarose Chitosan Viscoelastic properties abstract Hydrogel networks that combine suitable physical and biomechanical characteristics for tissue engineer- ing scaffolds are in demand. The aim of this work was the development of hydrogel networks based on agarose and chitosan using oxidized dextrins as low cytotoxicity crosslinking agents, paying special attention to the study of the influence of the polysaccharide composition and oxidation degree of the dextrins in the final characteristics of the network. The results show that the formation of an interpen- etrating or a semi-interpenetrating polymer network was mainly dependent on a minimum agarose con- tent and degree of oxidation of dextrin. Spectroscopic, thermal and swelling analysis revealed good compatibility with an absence of phase separation of polysaccharides at agarose:chitosan proportions of 50:50 and 25:75. The analysis of atomic force microscopy images showed the formation of a fibrillar microstructure whose distribution within the crosslinked chitosan depended mainly on the crosslinker. All materials exhibited the viscoelastic behaviour typical of gels, with a constant storage modulus inde- pendent of frequency for all compositions. The stiffness was strongly influenced by the degree of oxida- tion of the crosslinker. Cellular response to the hydrogels was studied with cells of different strains, and cell adhesion and proliferation was correlated with the homogeneity of the samples and their elastic properties. Some hydrogel formulations seemed to be candidates for tissue engineering applications such as wound healing or soft tissue regeneration. Ó 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Hydrogels are hydrophilic polymer networks characterized by the presence of physical or chemical crosslinks, entanglements and/or rearrangements of hydrophobic and hydrophilic domains. Due to the properties derived from this specific structure these sys- tems have found applications as biomaterials in biomedicine [1]. Both natural and synthetic polymers can be used for the synthesis of hydrogels, achieved by methods such as physical gelation, chemical crosslinking or self-assembly [2]. Polysaccharides are especially important since they play a role in domains involved in hydrophilicity, swelling, hydration, gelling, biodegradation, etc. Polysaccharides have a predominantly hydrophilic character and the presence of hydroxyl groups in their macromolecules makes possible the formation of intra- and interchain hydrogen bonds, however they also have a small hydrophobic character arising from–CH groups [3]. Due to their stereoregularity they often form helical conformations in solution that frequently lead to the forma- tion of physical gels. In addition, many polysaccharides have recog- nized biological activities [4,5] that contribute to cell–material interactions. It is for those reasons and because polysaccharides constitute a large family with a variety of chemical structures that they play a significant role in the field of biomaterials for tissue engineering [6]. Advances in tissue engineering have focused on the develop- ment of three-dimensional hydrogel scaffolds that provide suitable physical and biomechanical characteristics for cell culture [7]. Extracellular matrix (ECM) can be considered a semi-interpene- trating network (IPN) of a crosslinked protein material interlaced with high molecular weight molecules [8]. Hence, among the dif- ferent strategies to mimic ECM the preparation of semi-IPN [9] and IPN [10] hydrogels have received increasing attention. Semi- IPN and IPN hydrogels are an interesting class of systems based on a combination of one or two polymer networks that are physi- cally interlocked on the molecular scale without covalent bonds between polymeric chains of different type [11]. This approach is open to further research and, hence, the development of new 1742-7061/$ - see front matter Ó 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.actbio.2013.10.003 ⇑ Corresponding author at: Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. Tel.: +34 915618806; fax: +34 915644853. E-mail address: bvazquez@ictp.csic.es (B. Vázquez). Acta Biomaterialia xxx (2013) xxx–xxx Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat Please cite this article in press as: Gómez-Mascaraque LG et al. Oxidized dextrins as alternative crosslinking agents for polysaccharides: Application to hydrogels of agarose–chitosan. Acta Biomater (2013), http://dx.doi.org/10.1016/j.actbio.2013.10.003