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生物制剂递送至椎间盘的代谢修复:当前趋势。

Current trends in biologics delivery to restore intervertebral disc anabolism.

机构信息

Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.

Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.

出版信息

Adv Drug Deliv Rev. 2015 Apr;84:146-58. doi: 10.1016/j.addr.2014.08.008. Epub 2014 Aug 29.

Abstract

Low back pain is generally attributed to intervertebral disc (IVD) degeneration. This is a multifactorial disease induced by genetic and environmental factors and that progresses with aging. Disc degeneration is characterized by a limited ability of IVD cells to produce functional matrix while producing abnormal amounts of matrix-degrading enzymes. The prolonged imbalance between anabolism and catabolism in degenerative discs alters their composition and hydration. In turn, this results in increased angiogenesis and the loss of the disc's ability to maintain its aneural condition. Inflammation in the IVD, in particular the presence of pro-inflammatory cytokines, was found to favor innervation and also sensitization of the nociceptive pathways, thereby exacerbating degenerative symptoms. In this review, we discuss anti-inflammatory approaches to encounter disc catabolism, potential treatments to lower discogenic pain and pro-anabolic approaches in the form of protein delivery, gene therapy and cell delivery, to trigger regeneration in the IVD.

摘要

下腰痛通常归因于椎间盘(IVD)退变。这是一种由遗传和环境因素引起的多因素疾病,并随着年龄的增长而进展。椎间盘退变的特征是 IVD 细胞产生功能性基质的能力有限,同时产生异常数量的基质降解酶。退化椎间盘中合成代谢和分解代谢的长期失衡改变了它们的组成和水合作用。反过来,这导致血管生成增加和椎间盘维持其无神经状态的能力丧失。IVD 中的炎症,特别是促炎细胞因子的存在,被发现有利于神经支配,并使伤害感受途径敏感化,从而加重退行性症状。在这篇综述中,我们讨论了对抗炎症的方法来应对椎间盘的分解代谢,潜在的治疗方法来降低椎间盘源性疼痛,以及以蛋白质输送、基因治疗和细胞输送的形式促进椎间盘再生的促合成代谢方法。

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