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中山大学深圳校区《Advanced Healthcare Materials》| 超声引导可注射粘附性水凝胶实现深部不可压迫性伤口的靶向止血

  • 2026-05-23 21:04:49
中山大学深圳校区《Advanced Healthcare Materials》| 超声引导可注射粘附性水凝胶实现深部不可压迫性伤口的靶向止血

中山大学深圳校区刘杰团队开发了一种基于席夫碱反应的可注射天然聚合物水凝胶OPH,通过超声引导精准递送实现深部不可压迫性内脏伤口的快速止血与密封。相关成果以“Ultrasound-Guided Injectable Adhesive Hydrogel Enabling  Targeted Hemostasis in Deep and Incompressible Wounds”为题发表在《Advanced Healthcare Materials》期刊上。

亮点:创新性与突破

1、超声引导微创递送:首次将可注射水凝胶与实时超声引导结合,实现深部不可压迫性出血病灶的经皮精准定位与靶向注射,突破了传统止血材料难以到达深部创面的临床局限。

2、多功能一体化设计通过三组分席夫碱反应构建单一体系,同时实现室温快速成胶、强湿态粘附、高爆破压力耐受、自愈合、广谱抗菌及良好生物相容性,无需外源刺激或额外设备。

3、仿生协同止血机制整合物理封堵、共价键合、静电粘附与促凝激活多重作用,在致死性大血管出血模型中验证了优于商业产品的快速止血效能。

WHY:研究背景与意义

闭合性腹部创伤是临床中常见且危及生命的损伤类型,常伴随肝脏、脾脏等器官的大量出血。在手术条件受限的紧急情况下,立即有效地控制出血对提高患者存活率至关重要。然而,现有的临床止血策略(如ChitoFlex、QuikClot、Combat Gauze、Surgicel等传统止血材料)难以到达腹腔内深部且复杂的出血创面,这严重限制了它们的应用效果。与此同时,超声引导技术能够实现无创、实时的深部出血病灶可视化,为精准定位出血点提供了基础。因此,开发一种能够在超声引导下精准递送、适用于深部不可压迫性内脏伤口的止血材料,成为创伤急救领域亟待解决的临床需求。

WHAT:研究内容

本研究设计并构建了一种名为OPH的可注射、生物基止血水凝胶。该水凝胶通过化学修饰天然聚合物(透明质酸、壳聚糖和聚赖氨酸),利用醛基与氨基之间的席夫碱反应在室温下实现即时成胶,采用双联注射器系统无需额外热或光刺激即可完成原位注射。通过优化各组分比例,OPH水凝胶实现了约45 kPa的湿态粘附强度和123 mmHg的爆破压力耐受能力,能够有效抵抗动脉血压。体系中的阳离子组分赋予其对金黄色葡萄球菌和大肠杆菌的抗菌活性。研究进一步在兔肝脏闭合性创伤和致死性创伤模型中验证了该水凝胶的止血效果:在超声引导下,通过经皮穿刺将OPH水凝胶精准注射至出血核心部位,能够快速封闭伤口并控制出血,显著减少手术创伤和并发症。该工作通过快速共价交联、内在阳离子抗菌活性与超声引导精准递送的协同设计,为深部不可压迫性创伤的急救止血提供了一种高性能、微创化的治疗平台。

OPH 水凝胶的组成部分;体内大量肝脏血管出血的建模以及超声引导下的现场止血

HOW:研究方法

研究团队通过以下方法实现了这一创新:

    1、材料合成与表征:通过氧化透明质酸、羟丁基壳聚糖与聚赖氨酸的席夫碱反应构建A/B双组分可注射水凝胶,利用NMR、元素分析和电位滴定表征结构,结合扫描电镜、流变学测试及压缩实验评估微观形貌、凝胶化动力学、自愈合能力和力学性能。

    2、粘附与密封性能评价:采用猪皮搭接剪切实验测定湿态粘附强度,通过猪小肠爆破压力实验评估密封性能,并观察水凝胶溶胀行为以验证交联稳定性。

    3、生物学与止血性能评价:通过CCK-8、活死染色和溶血实验评价细胞毒性与血液相容性,建立体外全血凝血模型测定血液凝固指数,利用扫描电镜观察血细胞粘附形态,并通过抑菌圈法和生长曲线法评估抗菌活性。

    4、体内止血效果验证:在小鼠肝脏切口模型中比较不同材料的出血量与止血时间,通过皮下植入实验观察降解与炎症反应;在兔闭合性和致死性肝创伤模型中,利用超声引导经皮注射OPH凝胶,结合造影增强超声和剖腹探查验证深部止血效果。

    结论

    本文成功开发了一种基于天然聚合物的可注射AB型水凝胶粘合剂OPH,通过醛基与氨基之间的席夫碱反应实现室温快速交联成胶,利用动态亚胺键赋予其优异的自愈合性能;优化组分比例后,该水凝胶对湿组织的粘附强度可达约45 kPa,并能耐受超过动脉血压的爆破压力,同时壳聚糖和聚赖氨酸中的阳离子组分赋予其对革兰氏阳性菌和阴性菌的有效抑制作用;该水凝胶能够促进红细胞和血小板聚集以加速止血过程,在小鼠肝脏出血模型中实现了与商业产品相当的快速止血效果;结合超声引导精准递送技术,OPH水凝胶在兔闭合性和致死性肝脏创伤模型中均能有效定位并封闭出血灶,快速控制深部不可压迫性伤口的出血,为急诊条件下非压迫性出血的微创治疗提供了一种可行的策略。

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    文章来源:https://doi.org/10.1002/adhm.71187

    撰稿人:  巢妍霞

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    1. CONNECT:[ UseTime:0.001045s ] mysql:host=127.0.0.1;port=3306;dbname=c460;charset=utf8mb4
    2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.001698s ]
    3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.000701s ]
    4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.000695s ]
    5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.001465s ]
    6. SELECT * FROM `set` [ RunTime:0.000483s ]
    7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.001611s ]
    8. SELECT * FROM `article` WHERE `id` = 564651 LIMIT 1 [ RunTime:0.002036s ]
    9. UPDATE `article` SET `lasttime` = 1779746677 WHERE `id` = 564651 [ RunTime:0.025290s ]
    10. SELECT * FROM `fenlei` WHERE `id` = 64 LIMIT 1 [ RunTime:0.000723s ]
    11. SELECT * FROM `article` WHERE `id` < 564651 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.001326s ]
    12. SELECT * FROM `article` WHERE `id` > 564651 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.001809s ]
    13. SELECT * FROM `article` WHERE `id` < 564651 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.005721s ]
    14. SELECT * FROM `article` WHERE `id` < 564651 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.008478s ]
    15. SELECT * FROM `article` WHERE `id` < 564651 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.003789s ]
    0.235189s