  Citation: Chopra, H.; Bibi, S.; Kumar, S.; Khan, M.S.; Kumar, P.; Singh, I. Preparation and Evaluation of Chitosan/PVA Based Hydrogel Films Loaded with Honey for Wound Healing Application. Gels 2022, 8, 111. https://doi.org/10.3390/ gels8020111 Academic Editor: Rajendran JC Bose Received: 15 December 2021 Accepted: 7 February 2022 Published: 11 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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 Article Preparation and Evaluation of Chitosan/PVA Based Hydrogel Films Loaded with Honey for Wound Healing Application Hitesh Chopra 1 , Shabana Bibi 2,3 , Sandeep Kumar 4 , Muhammad Saad Khan 5 , Pradeep Kumar 6, * and Inderbir Singh 1, * 1 Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; chopraontheride@gmail.com 2 Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming 650091, China; shabana_bibi@ynu.edu.cn 3 The International Joint Research Center for Sustainable Utilization of Cordyceps Bioresources in China and Southeast Asia, Yunnan University, Kunming 650091, China 4 College of Pharmacy, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College, Ropar 140111, Punjab, India; sandeep_pharm70@yahoo.com 5 Department of Biosciences, Faculty of Sciences, COMSATS University Islamabad, Sahiwal 57000, Pakistan; saad.khan@cuisahiwal.edu.pk 6 Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa * Correspondence: pradeep.kumar@wits.ac.za (P.K.); inderbir.singh@chitkara.edu.in (I.S.) Abstract: In the present study, chitosan/polyvinyl alcohol (PVA)-based honey hydrogel films were developed for potential wound healing application. The hydrogel films were developed by a solvent- casting method and were evaluated in terms of thickness, weight variation, folding endurance, moisture content and moisture uptake. The water vapor transmission rate was found to range between 1650.50 ± 35.86 and 2698.65 ± 76.29 g/m 2 /day. The tensile strength and elongation at break were found to range between 4.74 ± 0.83 and 38.36 ± 5.39 N, and 30.58 ± 3.64 and 33.51 ± 2.47 mm, respectively, indicating significant mechanical properties of the films. SEM images indicated smooth surface morphology of the films. FTIR, DSC and in silico analysis were performed, which highlighted the docking energies of the protein–ligand complex and binding interactions such as hydrogen bonding, Pi–Pi bonding, and Pi–H bonding between the selected compounds and target proteins; hence, we concluded, with the three best molecules (lumichrome, galagin and chitosan), that there was wound healing potential. In vitro studies pointed toward a sustained release of honey from the films. The antimicrobial performance of the films was investigated against Staphylococcus aureus. Overall, the results signaled the potential application of chitosan/PVA based hydrogel films as wound dressings. Furthermore, in vivo experiments may be required to evaluate the clinical efficacy of honey-loaded chitosan/PVA hydrogel films in wound healing. Keywords: hydrogel films; chitosan/PVA; honey; wound healing 1. Introduction Every year numerous patients suffer from different types of skin epidermal damage such as burns, ulcers, and other traumatic incidents leading to the development of acute and/or chronic wounds [1]. Wound healing is a complex phenomenon that includes the inflammation phase, proliferation phase and tissue remodeling phase. Traditional wound dressings such as cotton wool and gauze still possess the largest part of the wound dressing market. Polymeric wound dressings may include films, foams, hydrogels, hydrocolloids and fibers [2]. Hydrogels are three-dimensional polymeric networks that are capable of absorbing water without dissolving [3]. Hydrogels have been explored for significant applications in wound healing, drug delivery, water purification, tissue engineering, scaffoldings, and 3D Gels 2022, 8, 111. https://doi.org/10.3390/gels8020111 https://www.mdpi.com/journal/gels