Colloids and Surfaces B: Biointerfaces 126 (2015) 35–43 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb Injectable in situ forming xylitol–PEG-based hydrogels for cell encapsulation and delivery Shivaram Selvam ∗ , Madhav V. Pithapuram, Sunita P. Victor, Jayabalan Muthu Polymer Science Division, BMT Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvanathapuram 695012, Kerala, India a r t i c l e i n f o Article history: Received 19 August 2014 Received in revised form 4 November 2014 Accepted 26 November 2014 Available online 15 December 2014 Keywords: Injectable hydrogels Cell encapsulation In situ crosslinkable Xylitol-based elastomers a b s t r a c t Injectable in situ crosslinking hydrogels offer unique advantages over conventional prefabricated hydro- gel methodologies. Herein, we synthesize poly(xylitol-co-maleate-co-PEG) (pXMP) macromers and evaluate their performance as injectable cell carriers for tissue engineering applications. The designed pXMP elastomers were non-toxic and water-soluble with viscosity values permissible for subcutaneous injectable systems. pXMP-based hydrogels prepared via free radical polymerization with acrylic acid as crosslinker possessed high crosslink density and exhibited a broad range of compressive moduli that could match the natural mechanical environment of various native tissues. The hydrogels dis- played controlled degradability and exhibited gradual increase in matrix porosity upon degradation. The hydrophobic hydrogel surfaces preferentially adsorbed albumin and promoted cell adhesion and growth in vitro. Actin staining on cells cultured on thin hydrogel films revealed subconfluent cell mono- layers composed of strong, adherent cells. Furthermore, fabricated 3D pXMP cell–hydrogel constructs promoted cell survival and proliferation in vitro. Cumulatively, our results demonstrate that injectable xylitol–PEG-based hydrogels possess excellent physical characteristics and exhibit exceptional cytocom- patibility in vitro. Consequently, they show great promise as injectable hydrogel systems for in situ tissue repair and regeneration. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Hydrogels are three-dimensional water swollen matrices formed by a network of crosslinked hydrophilic polymer chains that can be cast into any shape and size [1]. In addition, the ease of fabrication, tunable physical characteristics, predictable degrada- tion kinetics, and good biocompatibility make them apt candidates for a multitude of biomedical applications [2–4]. However, con- ventional hydrogel preparation methodologies deter the delivery of these hydrogel formulations to the site of injury in a minimally invasive fashion due to their inherent swelling behavior and vis- coelastic characteristics [5]. As a result, injectable hydrogel systems (IHS) that can gelate in situ upon administration have gained a lot of interest over the past few years [6,7]. These hydrogels are designed for direct administration into the body through simple injection delivery [8]. Mostly, such hydrogel systems are either cell encap- sulated or drug loaded aqueous solutions that crosslink in situ at the site of defect [8]. The hydrogel design principles of these injectable systems differ widely with their application and type of gelation ∗ Corresponding author. Tel.: +91 471 25250312. E-mail address: sselvam@sctimst.ac.in (S. Selvam). employed. Accordingly, they can be based on a simple sol–gel tran- sition system [6] or more complex composite systems [9]. IHS offer numerous advantages over conventional prefabricated hydrogels. These include smaller scar size, faster recovery time, less pain, and increased comfort and quality life of patients [10]. Furthermore, their minimally invasive nature reduces the risk of serious infectious complications which are commonly associated with invasive clinical procedures [5]. In addition, their high mold- ability can be exploited to fill the geometry of any tissue defect site without the need for glue or sutures [5,8]. However, several criteria need to be met for successful development of an injectable in situ gelling hydrogel system [8,10]. Firstly, the polymer precursors, crosslinkers, and initiators should be water-soluble, have sufficient low-viscosity and must easily flow through a small diameter hypodermic needle. Sec- ondly, gelation should follow simple chemical kinetics and proceed at an appropriate rate to maintain homogenous dispersion of cells/drug within the hydrogel matrix and to avoid untoward monomer toxicity or overheating at the injected site. Thirdly, like any biomaterial, the injected hydrogel should be biodegrad- able and their degradation products should be biocompatible and bioresorbable. In addition, cell-encapsulated IHS should provide a stable, cell-adhesive environment to foster cell growth and tissue http://dx.doi.org/10.1016/j.colsurfb.2014.11.043 0927-7765/© 2014 Elsevier B.V. All rights reserved.