Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Carrageenan-based functional hydrogel film reinforced with sulfur nanoparticles and grapefruit seed extract for wound healing application Lily Jaiswal, Shiv Shankar, Jong-Whan Rhim ⁎ Department of Food and Nutrition, BioNanocomposite Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea ARTICLE INFO Keywords: κ-Carrageenan Hydrogel film Sulfur nanoparticles Grapefruit seed extract Antibacterial activity Wound healing ABSTRACT κ-Carrageenan-based (Carr) functional wound healing hydrogel films were prepared by incorporating chitosan capped sulfur nanoparticles (SNP) and grapefruit seed extract (GSE). In vivo wound healing effect of the hydrogel films was tested using artificially wounded male Sprague-Dawley rats. The hydrogel film (Carr/GSE/SNP) showed higher mechanical strength, swelling ratio and ultraviolet barrier properties than the carrageenan film, but the water vapor permeability and water solubility were decreased. The hydrogel film showed antibacterial activity strong enough to destroy Staphylococcus epidermis and Escherichia coli within 3 h of incubation and showed high biocompatibility against mouse fibroblast (L929 cell lines). The hydrogel film (Carr/GSE/SNP3%) showed excellent wound healing effect (1.3% wound area after 2 weeks) compared to the control group (31% wound area after 2 weeks) through in vivo wound healing test. Histological examination showed the complete appearance of the healed epidermis. The Carr/GSE/SNP hydrogel films are most likely to be used for the treatment of full-thickness wounds. 1. Introduction Traditionally wound dressings such as gauze, lint, bandages, and cotton pads are used to protect the surface wound from contamination due to their hygroscopic properties, an affinity for skin, lack of toxicity, and availability (Shankar & Rhim, 2017). However, such dressing ma- terials have certain disadvantages such as limited absorption capacity of fluid exudates, insufficient wound coverage, and secondary injury caused by adherence to the wound (Li et al., 2017). Wound healing is a complex and dynamic process that recovers damaged tissue after se- quential nesting steps, including hemostasis, inflammation, prolifera- tion, and maturation (Lin et al., 2017). Since wounds are not immune to microbial invasion, choosing the ideal wound dressing material is a top priority, not only to prevent microbial penetration but also to accelerate the healing process with re-epithelization, reduce wound scarring and restore skin homeostasis (Martin, 1997). Hydrogels, three-dimensional hydrophilic networks composed of polymer chains linked by covalent bonds, hydrogen bonds, van der Waals interactions, or other physical or chemical bonds, have recently emerged as potential candidates for wound dressings due to their ex- cessive water/exudate absorbing capacity, maintaining a moist en- vironment, facilitating gas exchange, non-adherence, and adaptability to a variety of wound locations, as well as reducing pain and in- flammation by releasing bioactive compounds (Kamoun, Kenawy, & Chen, 2017). In particular, hydrogel-based wound dressings with anti- bacterial function can play an important role in wound dressing man- agement as they can provide additional protection against health- threatening infections. Recent developments in biopolymer-based functional composite films open up the possibility of developing hy- drogel-based wound dressings due to their unique physicochemical and functional properties such as biocompatibility, biodegradability, high absorption and moisture retention, antimicrobial activity, and non-cy- totoxic properties (Ahmed & Ikram, 2016; Jacob, Haponiuk, Thomas, & Gopi, 2018). κ-carrageenan, a natural sulfated polysaccharide extracted from the species of red seaweeds or macro-algae (Rhodophyceae), has been widely used for hydrogel manufacturing due to its gel formation and high water-holding capacity (Zia et al., 2017). Some limitations of κ-carrageenan-based hydrogels, such as low mechanical properties, have been attempted to solve by forming composites with functional nanomaterials (Roy, Shankar, & Rhim, 2019). Various functional materials such as Ag, CuO, ZnO, TiO 2 nano- particles and plant extracts or essential oils have been used to provide functional properties to hydrogel-based wound dressing materials (Oun & Rhim, 2017; Vijayakumar, Samal, Mohanty, & Nayak, 2019). As one of such functional filler materials, sulfur nanoparticle (SNP) has emerged (Shankar & Rhim, 2018b; Shankar, Pangeni, Park, & Rhim, 2018; Zahran, Hammadi, Al-dulaimi, & Sebaiy, 2018). Sulfur has long been used for a variety of dermatological treatments, including wound https://doi.org/10.1016/j.carbpol.2019.115191 Received 17 July 2019; Received in revised form 31 July 2019; Accepted 9 August 2019 ⁎ Corresponding author. E-mail address: jwrhim@khu.ac.kr (J.-W. Rhim). Carbohydrate Polymers 224 (2019) 115191 Available online 12 August 2019 0144-8617/ © 2019 Elsevier Ltd. All rights reserved. T