Bone morphogenetic protein delivery systems
Bone morphogenetic protein delivery systems
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DOI：
10.1097/00007632-200208151-00005
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发表时间：
2002-08-15
期刊：
影响因子：
3
通讯作者：
Li, R
中科院分区：
文献类型：
--
作者：
Seeherman, H;Wozney, J;Li, R
研究设计。进行了一项审查。回顾使用载体系统将骨形态蛋白运送到骨科修复部位的基本原理，并讨论常用的载体。背景资料摘要。脊柱融合术中骨形态发生蛋白的载体用于增加这些成骨因子在治疗部位的保留，并作为骨形成细胞的骨传导基质，同时保持骨形成的空间或体积。本文对相关文献进行了综述和讨论。尽管骨形态发生蛋白在小动物模型中以配方缓冲液的形式递送时可以诱导骨形成，但在大型动物模型和人体临床试验中，载体通常用于维持治疗部位成骨因子的浓度，使成骨细胞在足够的时间内向损伤区域迁移并增殖和分化。对于脊柱融合，载体也需要作为骨形成细胞的骨传导基质，同时保持骨形成的空间或体积。运载材料主要有四大类，分别是无机材料、合成聚合物、天然聚合物和前三种材料的复合材料。此外，同种异体骨已被用于将成骨因子输送到骨科修复部位。成骨载体组合的疗效往往是部位、特异性和物种特异性的。对成骨因子超生理浓度的要求可能与递送系统在治疗部位增加滞留时间和克服严格调控的能力有关。这些因素的抑制剂。在大型动物模型中，剂量的增加也可能与反应细胞数量的减少和骨形成速度的减慢有关。正在评估的新给药系统包括仓库给药系统、病毒载体系统、结合成骨因子给药系统和口服小分子靶点。输送系统在使用成骨因子增强脊柱融合和其他骨科修复中发挥重要作用。
Study Design. A review was conducted.Objectives. To review the rationale for the use of carrier systems to deliver bone morphogpnetic protein's to sites of orthopedic repair, and to discuss commonly used carriers.Summary of Background Data. Carriers for bone morphogenetic protein in spine fusion are used to, increase the retention of these osteogenic factors at the treatment site and to serve as an osteoconductive matrix for bone forming cells while maintaining a space or volume in which bone formation can occur.Methods. The literature is reviewed and discussed.Results. Although bone morphogenetic proteins can induce bone formation when delivered in formulation buffer in, small animal models, carriers often are used in larger animal models and human clinical trials to maintain the concentration of osteogenic factors at the treatment site,for a sufficient period to callow, bone-forming cella to migrate to the area of injury and to proliferate and differentiate. For spine fusion, carriers also are required to serve as an osteoconductive matrix for bone-forming cells While maintaining a space or volume in which bone formation Can occur. Four major categories of carrier materials are used for osteogenic factor delivery, inorganic materials, synthetic polymers, natural polymers, and composites, of the first three materials. In addition, allograft bone has been used to deliver osteogenic factors to I the-site of orthopedic repairs. The efficacy of osteogenic carrier combinations often is site, specific and species specific. The requirement for supraphysiologic concentrations of osteogenic factors may be related to the ability of the delivery system to increase the retention time, at the treatment site and overcome tight regulation. of these factors by their inhibitors. Dose escalation in large animal models also may be related to a decrease in the number of responding cell's and a slower rite of bone formation. New delivery systems being evaluated include depot delivery systems, viral vector systems, conjugated osteogenic factor delivery systems, and oral small molecule targets.Conclusions. Delivery systems play an important role in the use of osteogenic factors to augment spine fusions and other orthopedic repairs.