Citation: Carpa, R.; Farkas, A.; Dobrota, C.; Butiuc-Keul, A. Double-Network Chitosan-Based Hydrogels with Improved Mechanical, Conductive, Antimicrobial, and Antibiofouling Properties. Gels 2023, 9, 278. https://doi.org/10.3390/ gels9040278 Academic Editors: Yi Cao and Hai Lei Received: 10 March 2023 Revised: 25 March 2023 Accepted: 27 March 2023 Published: 29 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). gels Review Double-Network Chitosan-Based Hydrogels with Improved Mechanical, Conductive, Antimicrobial, and Antibiofouling Properties Rahela Carpa 1,2 , Anca Farkas 1,3, *, Cristina Dobrota 1,2 and Anca Butiuc-Keul 1,3 1 Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes , -Bolyai University, 1 M. Kogălniceanu Street, 400084 Cluj-Napoca, Romania; rahela.carpa@ubbcluj.ro (R.C.); cristina.dobrota@ubbcluj.ro (C.D.); anca.keul@ubbcluj.ro (A.B.-K.) 2 Institute for Research-Development-Innovation in Applied Natural Sciences, Babes , -Bolyai University, 30 Fântânele Street, 400294 Cluj-Napoca, Romania 3 Centre for Systems Biology, Biodiversity and Bioresource, Babes , -Bolyai University, 5–7 Clinicilor Street, 400006 Cluj-Napoca, Romania * Correspondence: ancuta.farkas@ubbcluj.ro Abstract: In recent years, the antimicrobial activity of chitosan-based hydrogels has been at the forefront of research in wound healing and the prevention of medical device contamination. Anti- infective therapy is a serious challenge given the increasing prevalence of bacterial resistance to antibiotics as well as their ability to form biofilms. Unfortunately, hydrogel resistance and biocom- patibility do not always meet the demands of biomedical applications. As a result, the development of double-network hydrogels could be a solution to these issues. This review discusses the most recent techniques for creating double-network chitosan-based hydrogels with improved structural and functional properties. The applications of these hydrogels are also discussed in terms of tissue recovery after injuries, wound infection prevention, and biofouling of medical devices and surfaces for pharmaceutical and medical applications. Keywords: antibiofouling; antimicrobial; chitosan-based hydrogel; double-network hydrogel 1. Introduction Hydrogels have received special attention due to their promising properties, such as softness, endowment, and high capacity to hold water [1,2]. The hydrophilic functional groups in the polymer’s backbone allow it to retain water, whereas crosslinks between network catena prevent it from dissolving [3,4]. Hydrogels can be created through either a physical or a chemical crosslinking process. Based on these two fundamental advances, there are numerous preparation paths for obtaining hydrogel structures. Physical crosslink- ers primarily consist of host–guest complexes, hydrophobic–hydrophobic, electrostatic, ionic, precipitation, and stereo complex coactions, followed by the development of polymer networks [5–8]. Physically crosslinked hydrogels have significant advantages in diverse bi- ological applications because they lack chemical crosslinkers, which could potentially cause unforeseeable and harmful side effects to the tissues. They are also more biocompatible. However, their reversible construction, low mechanics, and stability severely limited their range of applications [9–12]. The mechanical stability of physical crosslinking-produced hydrogels decreases as conditions change, such as temperature or pH [13–15]. In contrast to physical crosslinkers, chemical crosslinkers are created by covalently joining polymer chains. The network obtained is the result of highly efficient synthetic techniques such as free radical polymerization, click chemistry, Schiff’s base reaction, and photopolymerization [16,17]. Because of the irreversible connections between polymeric chains, chemically crosslinking hydrogels have stable constructions and superior mechanics, making them suitable for the tissue engineering sector. Chitosan-based hydrogels are Gels 2023, 9, 278. https://doi.org/10.3390/gels9040278 https://www.mdpi.com/journal/gels