一种天然多酚/普兰尼克凝胶在硬膜修复及神经保护中的应用基础研究

Dura injury is an intractable problem encountered during spine surgeries. Dural sealant gel is effective for aiding dura repair and diminishing postoperative complications. However, a more optimal dural sealant gel is still needed in clinical practice. On the other hand, comparing with dura injury, acute nerve injury is usually a more important problem in spine surgeries. Except for surgical decompression, other effective treatments for further improving neural functional prognosis are still absent. Therefore, it is clinical valuable to exploiting a novel dural sealant gel with effect of neuroprotection. Tannic acid is a group of natural polyphenol compound with effect of neuroprotection. In our previous work, a novel gel with excellent viscosity was synthesized with tannic acid and a polymer “Pluronic”. The components of this gel are simple and safe, which can avoid the probable drawback of difficulty for clinical translation while exploiting multifunctional materials. In this study, based on in vitro experiments as well as animal model of acute spinal cord injury and dura defect, we will investigate the effect and mechanism of neuroprotection, neural function improving and dura repair of this novel gel. Biocompatibility and biodegradation of this gel will also be investigated. We aim to prove the potential of this novel gel for treating acute spinal nerve injury and dura injury, so as to supply a new option for further improving the treatment results of these patients.

硬膜损伤是脊柱外科术中的棘手问题，而硬膜封闭凝胶是协助硬膜修复，减少术后并发症的有效手段，但目前临床上对于性能更优化的硬膜封闭凝胶仍存在需求。另一方面，急性神经损伤经常是脊柱术中更需要关注的问题。除去手术减压，临床上尚缺乏进一步改善神经损伤预后的有效手段。因此，开发一种兼具神经保护作用的新型硬膜封闭凝胶具有重要的临床意义。单宁酸是一种具有神经保护作用的天然多酚化合物。我们前期的研究发现，其可与聚合物普兰尼克反应形成凝胶，并具有较强的粘性。且该凝胶组分简单、安全无毒，避免了多功能材料研发时临床转化困难的可能弊端。本课题拟通过体外实验以及急性脊髓损伤和硬膜缺损的动物模型研究该凝胶的神经保护、促进神经功能恢复，以及粘合修复硬膜的治疗作用和机制，同时分析其生物相容性和生物降解等性能。最终证明其对脊柱急性神经损伤和硬膜损伤的治疗潜能。为临床上进一步提高脊柱神经和硬膜损伤的治疗效果提供新的选择。

硬膜损伤是脊柱外科术中的棘手问题，而硬膜封闭凝胶是协助硬膜修复，减少术后并发症的有效手段，但目前临床上对于性能更优化的硬膜封闭凝胶仍存在需求。另一方面，急性神经损伤经常是脊柱术中更需要关注的问题。除去手术减压，临床上尚缺乏进一步改善神经损伤预后的有效手段。因此，开发一种兼具神经保护作用的新型硬膜封闭凝胶具有重要的临床意义。单宁酸是一种具有神经保护作用的天然多酚化合物。我们将其与聚合物普兰尼克混合反应形成凝胶，通过体外实验以及基于急性脊髓损伤和硬膜缺损动物模型的体内实验，证明该凝胶具有良好的粘合封闭性能，可以有效粘合修复损伤的硬膜组织，防止脑脊液渗漏，并促进组织愈合。并且该凝胶可通过氧自由清除，神经细胞凋亡抑制，炎症调控，促进胶质瘢痕形成等作用机制发挥神经保护作用，从而促进小鼠急性脊髓损伤后的神经功能恢复。此外由于该凝胶组分简单、生物安全性高，合成方法简易，材料来源成本低廉。因此具有良好的进一步临床应用转化的潜能。