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琥珀酰壳聚糖-氧化透明质酸-氯化钙水凝胶作为止血剂。

-succinyl chitosan-oxidized hyaluronic acid-calcium chloride hydrogel as hemostatic agent.

机构信息

Biomedical Engineering Study Program, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Java, Indonesia.

Institute of Tropical Disease, Universitas Airlangga, Surabaya, Java, Indonesia.

出版信息

Int J Artif Organs. 2024 Nov;47(11):847-857. doi: 10.1177/03913988241280202. Epub 2024 Oct 3.

Abstract

This study aims to develop an effective hemostatic agent in the management of irregular and deep wounds that can accelerate the hemostatic process. The background revealed the importance of rapid treatment of bleeding, with data showing a significant risk of death from blood loss. Current treatments use conventional hemostatic dressings, but they are less effective on irregular surgical wounds. Several studies have developed chitosan, hyaluronic acid, and CaCl-based hydrogels that have hemostatic, regenerative, and antibacterial potential. However, there is still a need to develop hydrogels that are thermally stable, biocompatible, and able to accelerate the hemostatic process. This research will synthesize self-healing hydrogels by modifying the structure of chitosan and hyaluronic acid, using a certain ratio of ingredients. The research procedure was carried out with the preparation of -succinyl chitosan (NSC) and oxidized hyaluronic acid (OHA) as the main ingredients which were then added with CaCl to produce self-healing injectable hydrogel. First, NSC and OHA were dissolved in phosphate buffer solution (pH = 7.4 PBS) to obtain 60 mg/mL NSC and OHA solution respectively. Calcium chloride was then dissolved in water to obtain 120 mg/mL CaCl solution. Then NSC-OHA-CaCl-based hydrogels were synthesized through rapid and full solution mixing above room temperature with the composition of (1-1-0.1; 1-1-0.2; and 1-1-0.3). The targeted findings of this research are sample characterization results that explain and prove the best NSC-OHA-CaCl composition variation that can be used as a hemostatic agent for irregular and deep wounds. The results of the analysis obtained FTIR test data with the formation of C = N functional groups in the four samples; blood clotting time test for sample K0, K1, K2, and K3 with time 4.6, 3.33, 2.66, and 1 s; MTT assay with cell viability percentage of 77.82% for sample K0, 84.18% for sample K1, 89.30% for sample K2, and 89.50% for sample K3; hemolysis index percentage of 0.373% for sample K0, 0.555% for sample K1, 0.625% for sample K2, and 0.201% for sample K3; Viscosity test obtained data of 13 dPa s for sample K0, 15 dPa s for sample K1, 16 dPa s for sample K2, and 18 dPa. The injectability test yielded an injectability percentage of 96.84% for sample K0, 95.03% for sample K1, 94.78% dPa s for sample K2, and 94.61% for sample K3; the DSC test results of the four samples obtained a transition peak at the exothermic peak of 62.27°C for sample K0, 70.23°C for sample K1, 73.77°C for sample K2, and 74.49°C for sample K3; and the characteristic graph of the TGA test results, the weight profile of the hydrogel during heating which showed a mass change of 21.64 mg in sample K0, 16.89 mg in sample K1, 15.37 mg in sample K2, and 11.43 mg in sample K3 (°C).

摘要

本研究旨在开发一种有效的止血剂,用于管理不规则和深部伤口,以加速止血过程。研究背景揭示了快速治疗出血的重要性,数据显示出血导致死亡的风险显著增加。目前的治疗方法使用常规止血敷料,但它们在不规则手术伤口上的效果较差。几项研究已经开发出壳聚糖、透明质酸和基于 CaCl 的水凝胶,具有止血、再生和抗菌潜力。然而,仍需要开发热稳定、生物相容且能够加速止血过程的水凝胶。本研究将通过修饰壳聚糖和透明质酸的结构来合成自修复水凝胶,使用一定比例的成分。研究程序是通过制备 -琥珀酰壳聚糖(NSC)和氧化透明质酸(OHA)作为主要成分来进行的,然后加入 CaCl 以产生自修复可注射水凝胶。首先,将 NSC 和 OHA 溶解在磷酸盐缓冲溶液(pH = 7.4 PBS)中,分别得到 60mg/mL 的 NSC 和 OHA 溶液。然后将氯化钙溶解在水中,得到 120mg/mL 的 CaCl 溶液。然后通过在室温以上快速和完全混合溶液来合成 NSC-OHA-CaCl 基水凝胶,组成分别为(1-1-0.1;1-1-0.2;和 1-1-0.3)。本研究的目标发现是样品特征化结果,解释和证明了最佳的 NSC-OHA-CaCl 组成变化,可作为不规则和深部伤口的止血剂。分析获得的傅里叶变换红外(FTIR)测试数据表明,四个样品中形成了 C = N 官能团;K0、K1、K2 和 K3 样品的凝血时间测试分别为 4.6、3.33、2.66 和 1 s;MTT 测定 K0 样品的细胞存活率为 77.82%,K1 样品为 84.18%,K2 样品为 89.30%,K3 样品为 89.50%;溶血指数百分比 K0 样品为 0.373%,K1 样品为 0.555%,K2 样品为 0.625%,K3 样品为 0.201%;粘度测试得到 K0 样品的 13dPa·s、K1 样品的 15dPa·s、K2 样品的 16dPa·s 和 K3 样品的 18dPa·s。可注射性测试得到 K0 样品的可注射性百分比为 96.84%,K1 样品为 95.03%,K2 样品为 94.78%,K3 样品为 94.61%;四个样品的差示扫描量热法(DSC)测试结果在 62.27°C 处获得放热峰的相变峰,K0 样品为 70.23°C,K1 样品为 73.77°C,K2 样品为 73.77°C,K3 样品为 74.49°C;和热重分析(TGA)测试结果的特征图,水凝胶在加热过程中的重量分布显示 K0 样品的质量变化为 21.64mg,K1 样品为 16.89mg,K2 样品为 15.37mg,K3 样品为 11.43mg(°C)。

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