Antibacterial and hemostatic hydrogel via nanocomposite from cellulose nanofibers

Highlights

• The CNF/G/Ag_0.5 hydrogel has stronger mechanical and self-recovery property.

• The CNF/G/Ag_0.5 hydrogel has satisfactory antibacterial and hemostatic performance.

• The CNF/G/Ag_0.5 hydrogel showed good biocompatibility and wound healing efficacy.

Abstract

Bacterial infection and uncontrolled bleeding are the major challenges facing the wound treatment. In order to solve these problems, we have devised a green nanocomposite hydrogel by introducing the aminated silver nanoparticles (Ag-NH₂ NPs) and gelatin (G) to carboxylated cellulose nanofibers (CNF). Interpenetrating polymeric network (IPN) was formed by interaction of multicomponent, leading to the non-covalent (dynamic ionic bridges) crosslinked hydrogel CNF/G/Ag. The produced hydrogel dressing with 0.5 mg/mL Ag-NH₂ NPs (CNF/G/Ag_0.5) demonstrated stronger mechanical, self-recovery, antibacterial properties, satisfactory hemostatic performance, and appropriate balance of fluids on the wound bed (2093.9 g/m² per day). More importantly, the wound healing model evaluation in vitro and in vivo of CNF/G/Ag_0.5 showed an outstanding biocompatibility (∼100% infected cell viability) and wound healing efficacy (∼90% healed and 83.3% survival after 14 days). Our study paved a highly promising approach to improve the performance of cellulose-based hydrogel dressing and would also be useful for developing ideal skin wound dressings by other green materials.

Introduction

The skin is the essential interface between the body and its environment which can heal itself when the wound is narrow and small. However, the large wound of human skin is prone to infection and difficult to heal. Therefore, to help wound healing, appropriate treatments to the wound are necessary (Li et al., 2015). The conventional wound dressing in clinical application is natural or synthetic bandages, cotton wool, and gauzes, which may need long-term treatment, be ineffective, or even adhere to desiccated wound surfaces (Radhakumary, Antonty, & Sreenivasan, 2011). In order to overcome many of these drawbacks, numerous wound dressing materials were being investigated (Çalamak, Erdoğdu, Özalp, & Ulubayram, 2014; Fan et al., 2014; Ignjatović et al., 2016; Kang et al., 2017; Mei et al., 2017). Among them, hydrogel-based wound dressing have been paid special attentions due to that it can possess many essential properties, such as providing a cooling sensation, a moist environment, allowing gaseous exchange and wound exudate absorption (Cheng et al., 2017; Li et al., 2017; Zhao et al., 2017). Unfortunately, up to now, there is almost no clinically used hydrogel satisfying with all the requirements of the ideal skin wound dressing.

The leading challenge facing the wound dressing is the uncontrolled hemorrhage which is often the direct cause of the trauma deaths (Gaston, Fraser, Xu, & Ta, 2018; Konieczynska et al., 2017). Many clinical hemostatic formulations work with the use of hemostatically active proteins such as fibrin, collagen, and thrombin, but may be difficult to store and use out of the hospital. Gelatin (G) is an interesting candidate as a hemostatic based on its low prices, widely distribute, hydrolysis into simple byproducts, and reliable hemostatic effect (Chen, Guo et al., 2016; Lan et al., 2015; Mele, 2016). For the aspect of wound contamination, the major reason is bacterial infection causing by Staphylococcus aureus and Pseudomonas aeruginosa, which can easily enter the body through the wounds, reach into deeper portions of the tissue, furthermore, even lead to septicemia and death. In order to reduce the abuse of broad-spectrum antibiotic, many antibiotics alternatives, such as silver nanoparticles (Ag NPs) with low bacterial resistance and side effects, have been widely used as topical antibacterial agents (Chen, Zhang et al., 2016; Dhand et al., 2016; Nie et al., 2016). But the development and application of nanomaterials has generated public debate on the safety of nanotechnology and has been intervened by some supervisory departments. This issue could potentially be overcame by incorporation of nanoparticles into hydrogels resulting in decreased risks to human health and the environment (Foss Hansen et al., 2016; Thoniyot, Tan, Karim, Young, & Loh, 2015).

Interpenetrating polymeric network (IPN) is a 3D network composed of two or more different types of materials, which are partially or fully interlaced on a molecular scale but not covalently bonded to each other and cannot be separated unless chemical bonds are broken (Dragan, 2014). Multicomponent hydrogels based on IPNs have shown structural diversity, versatility, significant enhancement in the mechanical performance for tissue healing. Cellulose nanofibers (CNF), a kind of green functional material, have been widely studied in the field of food and biomedical field due to their nontoxic, biocompatible, biodegradable, and environmental and economic sustainability (Fernandes, Pires, Mano, & Reis, 2013; Liu et al., 2018; Saito, Kimura, Nishiyama, & Isogai, 2007). TEMPO-oxidized cellulose nanofibers (carboxylated CNF) have good hydrophilicity and water retention, which can helpful to achieve good performance on blood absorption and water vapor transmission. To the best of our knowledge, cellulose-based multifunctional hydrogel dressing was rarely reported. It is well accepted that cellulose and other biopolymers are promising building blocks of sustainable materials with tailored characteristics (Fan et al., 2017).

In this article, we presented a novel design for a CNF/G/Ag nanoparticles hydrogel as a wound dressing which did meet the controlling of evaporative water loss, the stopping hemorrhage, and the good antibacterial and biocompatible properties to promote wound healing. The physical and chemical properties, bactericidal activities, safety as well as the wound healing efficiency were comparatively investigated.