Wang Wantao, Liu Lei, Ma Wenzheng, Zhao Lei, Huang Lin, Zhou Dan, Fan Jinghao, Wang Jianru, Liu Hongmei, Wu Decheng, Zheng Zhaomin
Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, 510080, People's Republic of China.
Pain Research Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
Bioact Mater. 2024 Jul 26;41:355-370. doi: 10.1016/j.bioactmat.2024.07.031. eCollection 2024 Nov.
Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.
氧化应激和衰老导致髓核(NP)细胞进行性衰老,从而引发椎间盘(IVD)退变(IVDD)。在某些情况下,退变的IVD可进一步导致腰痛(LBP)。多项研究证实,延缓和逆转NP细胞衰老可减轻IVDD。然而,IVD相对封闭的组织结构给抗衰老药物的局部应用带来了挑战。在此,我们通过将苯基硼酸修饰的甲基丙烯酰化明胶(GP)与槲皮素偶联制备了一种抗衰老水凝胶,以通过清除衰老的NP细胞来减轻IVDD。该水凝胶具有可注射性、生物可降解性、显著的生物相容性以及在病理条件下槲皮素的响应性释放。体外实验表明,该水凝胶可降低衰老标志物的表达并恢复衰老NP细胞的代谢平衡。体内研究证实,在大鼠模型中原位单次注射该水凝胶可维持IVD组织结构并减轻对有害机械力的敏感性,表明这是一种改善IVDD和LBP的潜在治疗方法。这种方法有助于预防与全身给药相关的潜在全身毒性,并降低因向IVD重复注射游离药物而导致的发病率,为IVDD治疗提供了一种新策略。