Cheng Xueliang, Zhang Zhen, Ren Hui, Zou Zheng, Zhang Yu, Qu Yang, Chen Xuesi, Zhao Jianwu, He Chaoliang
CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Department of Orthopedics, The Second Norman Bethune Hospital of Jilin University, Changchun 130014, China.
Natl Sci Rev. 2024 Apr 30;11(6):nwae160. doi: 10.1093/nsr/nwae160. eCollection 2024 Jun.
Dural defects and subsequent complications, including cerebrospinal fluid (CSF) leakage, are common in both spine surgery and neurosurgery, and existing clinical treatments are still unsatisfactory. In this study, a tissue-adhesive and low-swelling hydrogel sealant comprising gelatin and -phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) is developed via the OPA/amine condensation reaction. The hydrogel shows an adhesive strength of 79.9 ± 12.0 kPa on porcine casing and a burst pressure of 208.0 ± 38.0 cmHO. The hydrogel exhibits a low swelling ratio at physiological conditions, avoiding nerve compression in the limited spinal and intracranial spaces. In rat and rabbit models of lumbar and cerebral dural defects, the 4aPEG-OPA/gelatin hydrogel achieves excellent performance in dural defect sealing and preventing CSF leakage. Moreover, local inflammation, epidural fibrosis and postoperative adhesion in the defect areas are markedly reduced. Thus, these findings establish the strong potential of the hydrogel sealant for the effective watertight closure of dural defects.
硬膜缺损及随后的并发症,包括脑脊液(CSF)漏,在脊柱手术和神经外科手术中都很常见,而现有的临床治疗仍不尽人意。在本研究中,通过邻苯二甲醛(OPA)/胺缩合反应开发了一种由明胶和OPA封端的四臂聚乙二醇(4aPEG-OPA)组成的组织粘合剂和低膨胀水凝胶密封剂。该水凝胶在猪肠衣上的粘附强度为79.9±12.0 kPa,破裂压力为208.0±38.0 cmH₂O。该水凝胶在生理条件下具有低膨胀率,可避免在有限的脊柱和颅内空间中压迫神经。在大鼠和兔的腰椎和脑硬膜缺损模型中,4aPEG-OPA/明胶水凝胶在硬膜缺损密封和预防脑脊液漏方面表现出色。此外,缺损区域的局部炎症、硬膜外纤维化和术后粘连明显减少。因此,这些发现表明水凝胶密封剂在有效水密闭合硬膜缺损方面具有巨大潜力。