Intervertebral disc herniation (IVDH) is a common manifestation of intervertebral disc degeneration (IVDD) characterized by inflammation that results in the rupture of the annulus fibrosus (AF) and herniation of the nucleus pulposus (NP). While current clinical research primarily focuses on regulating the degenerative NP, the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc (IVD) has been overlooked. Resolving immunoregulation and AF repair is imperative to effectively prevent recurrent herniation. Therefore, this study introduces a bioactive sealant (OD/GM/QCS-sEVs), which combines gelatin methacryloyl (GM) and oxidized dextran (OD) with quaternized chitosan (QCS) and incorporates small extracellular vesicles (sEVs). The developed sealant possesses injectability, self-healing capabilities, tissue adhesiveness, and mechanical stability, with an average adhesive strength of 109.63 kPa In vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal IVD. Additionally, the sealant releases sEVs through a pH-responsive mechanism, thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling pathway. This mechanism facilitates immunoregulation and anti-inflammatory effects, and promotes stem cell differentiation into fibrocartilage. Animal experiments confirm the ability of OD/GM/QCS-sEVs to seal defects, prevent proteoglycan loss, inhibit IVDD development, and promote AF regeneration. Overall, OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration.

中文翻译：

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细胞外囊泡负载双网络生物活性密封剂通过免疫调节和纤维环修复治疗椎间盘突出症

椎间盘突出症（IVDH）是椎间盘退变（IVDD）的常见表现，其特征是炎症导致纤维环（AF）破裂和髓核（NP）突出。虽然目前的临床研究主要集中在调节退行性 NP，但 AF 在维持椎间盘（IVD）机械稳定性和代谢平衡中的关键作用却被忽视了。解决免疫调节和房颤修复对于有效预防复发性脑疝至关重要。因此，本研究引入了一种生物活性密封剂（OD/GM/QCS-sEVs），它将明胶甲基丙烯酰（GM）和氧化葡聚糖（OD）与季铵化壳聚糖（QCS）相结合，并结合了小细胞外囊泡（sEVs）。所开发的密封剂具有可注射性、自愈能力、组织粘附性和机械稳定性，平均粘附强度为109.63 kPa。体外实验表明，OD/GM/QCS-sEVs可以有效密封AF缺陷，同时保持与传统密封剂相当的机械性能。正常的 IVD。此外，密封剂通过 pH 响应机制释放 sEV，从而通过 NF-κB 信号通路将巨噬细胞极化调节为 M2 表型。这种机制有利于免疫调节和抗炎作用，并促进干细胞分化为纤维软骨。动物实验证实了 OD/GM/QCS-sEV 具有封闭缺陷、防止蛋白聚糖损失、抑制 IVDD 发育和促进 AF 再生的能力。总体而言，OD/GM/QCS-sEVs有望成为一种创新的生物活性封闭剂，通过解决免疫调节和房颤再生问题来治疗复发性疝气。