Fracture repair with ultrasound: Clinical and cell-based evaluation
Fracture repair with ultrasound: Clinical and cell-based evaluation
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DOI：
10.2106/jbjs.g.01218
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发表时间：
2008-02-01
影响因子：
5.3
通讯作者：
Laurencin, Cato T.
中科院分区：
文献类型：
--
作者：
Khan, Yusuf;Laurencin, Cato T.
骨折修复在临床领域和基础研究层面继续得到广泛研究，部分原因是 5% 至 10% 的骨折导致延迟愈合或不愈合，具体取决于不完全愈合的持续时间。除了修复的时间延迟之外，骨不连还具有相同的统一特征：所有骨膜和骨内膜修复过程都已停止，骨折无需手术干预即可自行愈合。一种侵入性较小的替代方法——低强度脉冲超声——已显示出作为延迟愈合和不愈合的治疗方法以及促进牵引成骨的方法的前景。在本文中，我们总结了低强度脉冲超声在骨折修复、骨不连治疗和牵引成骨方面的临床有效性，并讨论了大量已发表研究的结果，这些研究试图通过对成骨细胞和成骨细胞前体的低强度脉冲超声暴露的研究来阐明其有效性背后的机制。在临床评估中，低强度脉冲超声被证明可以增强骨修复（最常见的是缩短愈合时间），尽管患者群体的差异阻碍了临床有效性的明确声明。体外细胞评估和动物模型体内研究表明，低强度脉冲超声照射后，细胞增殖、蛋白质合成、胶原蛋白合成、膜通透性、整合素表达、胞质 Ca2+ 水平增加以及其他骨修复指标增加。许多细胞对低强度脉冲超声的反应反映了细胞对流体诱导剪切流的反应，表明两者之间存在联系，是一种潜在的作用机制。关于成骨细胞在低强度脉冲超声照射下的行为已揭示的大量信息表明，其确切的作用机制是复杂的。然而，很明显，在揭示这些机制方面正在取得相当大的进展，这有助于鼓励在新应用中使用低强度脉冲超声。据认为，成功的非侵入性治疗策略（例如低强度脉冲超声）可以与其他传统和新颖的组织再生策略相结合，以开发针对大规模骨缺损的新疗法。
Fracture repair continues to be widely investigated, both within the clinical realm and at the fundamental research level, in part due to the fact that 5% to 10% of fractures result in either delayed union or nonunion, depending on the duration of incomplete healing. Beyond the temporal delay in repair, nonunions share the same unifying characteristic: all periosteal and endosteal repair processes have stopped and the fracture will riot heal without surgical intervention. A less-invasive alternative method-low-intensity pulsed ultrasound-has shown promise as a treatment for delayed unions and nonunions and as a method to facilitate distraction osteogenesis. In this paper, we summarize the clinical effectiveness of low-intensity pulsed ultrasound with regard to fracture repair, treatment of nonunion, and distraction osteogenesis and we discuss the results of a multitude of published studies that have sought to elucidate the mechanisms behind that effectiveness through research on low-intensity pulsed ultrasound exposure on osteoblasts and osteoblast precursors. When evaluated clinically, low-intensity pulsed ultrasound was shown to enhance bone repair (most commonly noted as a decrease in healing time), although variations in patient population hindered a definitive claim to clinical effectiveness. In vitro cellular evaluation and in vivo studies on animal models have revealed an increase in cell proliferation, protein synthesis, collagen synthesis, membrane permeability, integrin expression, and increased cytosolic Ca2+ levels as well as other increased indicators of bone repair in response to low-intensity pulsed ultrasound exposure. Many of the cellular responses to low-intensity pulsed ultrasound mirror the cellular responses to fluid-induced shear flow, suggesting a link between the two as one potential mechanism of action. The considerable amount of information that has been revealed about the behavior of osteoblasts under low-intensity pulsed ultrasound exposure suggests that the exact mechanism of action is complex. It is clear, however, that considerable progress is being made toward uncovering these mechanisms, which has served to encourage the use of low-intensity pulsed ultrasound in new applications. It is posited that successful noninvasive treatment strategies such as low-intensity pulsed ultrasound may be combined with other conventional and novel tissue-regeneration strategies to develop new treatments for large-scale bone defects.