Optimization of protein crosslinking formulations for the treatment of degenerative disc disease.
Optimization of protein crosslinking formulations for the treatment of degenerative disc disease.
复制标题
用于治疗退行性椎间盘疾病的蛋白质交联配方的优化。
DOI：
10.1097/brs.0b013e3181cc3de9
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发表时间：
2011
期刊：
影响因子：
3
通讯作者：
Hedman,Tom
中科院分区：
文献类型：
--
作者：
Slusarewicz,Paul;Zhu,Keng;Kirking,Bryan;Toungate,Justin;Hedman,Tom
研究设计：生物化学研究，旨在优化用于治疗退行性椎间盘疾病的蛋白质交联制剂，并随后对用这些制剂治疗的组织进行生物力学测试。目的：优化用于治疗退行性椎间盘疾病的蛋白质交联制剂。背景资料概要：非手术外源性交联疗法是治疗退行性椎间盘疾病的一种潜在的新的非侵入性技术。该技术是基于注射的蛋白质交联剂到病理盘恢复其机械性能，也有可能增加组织的渗透性，从而促进废物和nutrities.Methods的交换京尼平（GP）的扩散监测注射到椎间盘和表面活性剂对扩散的影响进行了研究。GP和甲基乙二醛（MG）的配方进行了生化优化，并用于治疗牛椎间盘。他们对牛纤维环组织的影响进行了评估，使用周向拉伸试验，而GP配方也进行了测试，其能力，以减少磁盘凸起下load.Results.GP表现出明显的时间依赖性扩散和十二烷基硫酸钠，但不是吐温-20，增强扩散30%。两种交联剂，GP和MG，被胺抑制，但被磷酸根离子增强。这两种制剂可以提高牛纤维环组织的一些物理参数，而GP制剂可以减少椎间盘隆起后注射到spinal discs.Conclusion.配方缺乏胺和含有磷酸根离子似乎是有前途的候选人的交联剂GP和MG的临床应用。
Study Design.Biochemical studies aimed at optimization of protein crosslinking formulations for the treatment of degenerative disc disease and subsequent biomechanical testing of tissues treated with these formulations.Objective.To optimize protein crosslinking formulations for treatment of degenerating spinal discs.Summary of Background Data.Nonsurgical exogenous crosslinking therapy is a potential new, noninvasive technology for the treatment of degenerative disc disease. The technology is based on the injection of protein crosslinking reagents into the pathologic disc to restore its mechanical properties and also to potentially increase the permeability of the tissue and so facilitate the exchange of waste products and nutrients.Methods.Diffusion of genipin (GP) was monitored following injection into spinal discs and the effects of surfactants on diffusion studied. Formulations for GP and methylglyoxal (MG) were biochemically optimized and used to treat bovine spinal discs. Their effects on bovine anulus tissue were evaluated using a circumferential tensile test, while the GP formulation was also tested with respect to its ability to reduce disc bulge under load.Results.GP exhibited a distinct time-dependent diffusion and sodium-dodecyl-sulfate, but not Tween-20, enhanced diffusion by 30%. Two crosslinkers, GP and MG, were inhibited by amines but enhanced by phosphate ions. Both formulations could enhance a number of physical parameters of bovine anulus tissue, while the GP formulation could reduce disc bulge following injections into spinal discs.Conclusion.Formulations lacking amines and containing phosphate ions appear to be promising candidates for clinical use of the crosslinkers GP and MG.