A novel hydrogel based on Bletilla striata polysaccharide for rapid hemostasis: Synthesis, characterization and evaluation

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Abstract

The purpose of this study is to develop a new polysaccharide-based hydrogel. The Box-Behnken design was used to optimize the optimal synthesis conditions of the hydrogel, with the swelling parameters as indicators. The findings of rheologic tests confirm that free radical polymerization and the introduction of linear polymers improved the mechanical strength of the hydrogel. Combined with the characterization results, the gel mechanism of BSP-g-PAA/PVA DN hydrogel was proposed. The intermolecular association and entanglement increase, which effectively dissipates energy, thereby enhancing the mechanical properties of the hydrogel. In vitro blood compatibility experiments show that DN hydrogel has a low hemolysis rate and a good coagulation effect. The material is non-cytotoxic to L929 cells. The hepatic haemorrhage and mouse-tail amputation models of rats and mice were used to further evaluate the in vivo wound sealing and hemostatic properties of the hydrogel. The blood loss and hemostatic time were significantly lower than those of the control group, indicating that the hydrogel has excellent hemostatic effects. Therefore, the obtained BSP-g-PAA/PVA DN network hydrogel has good comprehensive properties and is expected to be used as a hemostatic material or a precursor of a drug carrier and a tissue engineering scaffold.

Introduction

The healing behaviour of wounds, such as incisions, burns and scalds, has attracted worldwide attention due to the high coordination and complexity [1]. Uncontrollable bleeding is one of the tricky conditions, which can lead to haemorrhagic shock, organ failure, and is characterized by high incidence and high mortality [2], [3]. For tissues with abundant capillaries, conventional hemostatic materials such as gauze may cause secondary damage when pressed or peeled off [4]. The ideal hemostatic material should provide sufficient mechanical strength and tissue adhesion to seal the incision site without hindering tissue function or movement [5]. The hydrogel material has the characteristics of high porous density, water retention, good viscoelasticity, and softness, which can achieve rapid hemostasis by promoting platelet aggregation and promoting hemostasis [6]. They are suitable as novel hemostatic materials to assist wound healing and have broad application prospects in the field of wound care.

The general advantages of hydrogel materials are non-toxic, non-sensitizing, and strong water absorption. Hydrogels composed of synthetic materials tend to have better mechanical strength, while hydrogels composed of natural materials have the charm of pharmacological activity [7], [8]. The interpenetrating polymer network can not only ensure good mechanical strength, tissue adhesion, but also reflect pharmacological activity [9], [10], which makes it one of the popular research directions of hydrogel materials.

Some natural polymers are widely used as hydrogel materials due to their structural properties, excellent biocompatibility, low toxicity and biodegradability. B. striata is a traditional astringent hemostatic Chinese herbal medicine with excellent blood clotting ability and has been widely used for treatment of various haemorrhagic diseases, such as gastrointestinal bleeding, cough and haemoptysis, gastric and duodenal ulcer, and traumatic diseases [11], [12]. BSP can provide an environment suitable for wound healing, up-regulate vascular endothelial growth factor, promote the proliferation and migration of vascular endothelial cells and fibroblasts, and the formation of epithelial tissue [13]. However, the lack of mechanical strength and water absorption of BSP limits its application [14], which makes it used be prepared into sponge [15], film [16], drug delivery microneedle [17] and other preparations that do not require high mechanical properties. BSP can be prepared it into fibers by wet spinning, maintaining a certain mechanical strength by means of hydrogen bonds between the fibers [18], [19]. BSP was oxidized and cross-linked to prepare a hydrogel [20]. But these materials have difficulties such as long synthesis time or slightly harsh reaction conditions.

In this study, a one-pot method was used to graft BSP rich in carboxyl and hydroxyl groups with the hydrophilic monomer acrylic acid (AA) [21], and introduced linear polymer polyvinyl alcohol (PVA) to form a double network [22]. This research is proposed to develop a novel polysaccharide-based hydrogel as a wound dressing or drug carrier, focused on the influence of the concentration of each graft-related reagent on the morphology and rheological property es of the obtained hydrogel.

Section snippets

Materials

Tubers of Bletilla striata were purchased from Shanghai Kangqiao Traditional Chinese Medicine Pieces Co., Ltd. The powder of Bletilla striata polysaccharide (BSP) was extracted under optimized conditions, using the same procedure as described by Chen et al [23]. And the detailed information about BSP was supplied in the supplementary materials. Ammonium persulfate (APS), acrylic acid (AA), methylene-bis-acrylamide (MBA), polyvinyl alcohol (PVA) was analytical grade and purchased from Sinopharm

FTIR analysis

The chemical structure of the BSP-g-PAA/PVA DN network hydrogel was displayed by FTIR, as shown in Fig. 1A. The absorption band at 2910–2938 cm−1 is attributed to CH2 group Csingle bondH stretching. And there is a broad and strong absorption peak at 3300 cm−1, which is attributed to hydroxyl group Osingle bondH stretching. The FTIR spectrum of pure BSP is a typical polysaccharide dominant frequency signal at 400–4000 cm−1: glucose has an absorption peak at 1012.6 cm−1 and 1148.8 cm−1, and the peak at 842.7 cm−1

Conclusions

A novel hydrogel based on natural polysaccharide was prepared by the one-pot water polymerization method. The Box-Behnken design was used to optimize the optimal synthesis conditions of the hydrogel, with the gel fraction and the swelling ratio under distilled water and normal saline as indicators. It reflects the evidence that the respective variables have a significant influence on the swelling ability of the hydrogel. After fitting the swelling curves to Schott's pseudo-second-order kinetic

CRediT authorship contribution statement

Jinxi Xiang: Conceptualization, Methodology, Writing-Original draft preparation.

Youjie Wang: Data curation, Software.

Luping Yang: Investigation, Cell-related experiments.

Xiaojia Zhang: Extraction, purification and characterization of polysaccharides.

Yanlong Hong: Supervision.

Lan Shen: Writing- Reviewing and Editing.

Acknowledgement

This work was supported by the Natural Science Foundation of Shanghai (No: 19ZR1457700 and No: 20ZR1458400), the Three-year Action Plan for the Development of Traditional Chinese Medicine funded by Shanghai Municipal Health Planning Commission (No: ZY (2018-2020)-CCCX-2001-03) and the Graduate Student Innovation Ability Project of Shanghai University of Traditional Chinese Medicine, China (No. A2-C202050102040107).

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