Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial sealants in aqueous environments. To evaluate the performance of DTA in the range of intracranial pressure typical of healthy and disease states, ex vivo burst pressure testing was conducted until failure after DTA or commercial sealant application on ex vivo porcine dura with a punch biopsy injury. In contrast to commercial sealants, DTA remained adhered to the porcine dura through increasing pressure up to 300 millimeters of mercury and achieved a greater maximum burst pressure. Feasibility of DTA to repair cerebrospinal fluid leak in a simulated surgical context was evaluated in postmortem human dural tissue. DTA supported effective sutureless repair of the porcine thecal sac in vivo. Biocompatibility and adhesion of DTA was maintained for up to 4 weeks in rodents after implantation. The findings suggest the potential of DTA to augment or perhaps even supplant suture repair and warrant further exploration.

中文翻译：

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坚韧的生物粘附水凝胶支持猪和离体人体组织中硬脑膜的无缝密封

硬脑膜对中枢神经系统组织和脑脊液的完全隔离是维持体内平衡和正常器官功能的基础，使得该层的重建成为神经外科手术中的重要步骤。尽管面临技术、微环境和解剖学方面的挑战，但通过缝合修复对硬脑膜进行初步闭合是当前的标准。在这里，我们应用机械坚韧的水凝胶与生物粘合剂配对，用于啮齿动物、猪和人类中枢神经系统组织中的硬脑膜的术中密封。拉伸测试表明，与水性环境中的商用密封剂相比，这种硬脑膜坚韧粘合剂 (DTA) 表现出更高的韧性、更高的最大应力和拉伸力。为了评估 DTA 在健康和疾病状态典型颅内压范围内的性能，在对具有穿刺活检损伤的离体猪硬脑膜进行 DTA 或商业密封剂应用后，进行离体爆裂压力测试直至失败。与商业密封剂相比，DTA 通过将压力增加至 300 毫米汞柱而保持粘附在猪硬脑膜上，并实现了更大的最大爆破压力。在死后的人类硬脑膜组织中评估了 DTA 在模拟手术环境中修复脑脊液漏的可行性。 DTA 支持体内猪鞘囊的有效无缝修复。植入后，DTA 在啮齿类动物中的生物相容性和粘附性可维持长达 4 周。研究结果表明 DTA 具有增强甚至取代缝合修复的潜力，值得进一步探索。