Analysis of the rib construct for treatment of early-onset spinal deformity with hyperkyphosis

项目摘要/摘要 早发性脊柱畸形(EOSD)是一种常见的儿童早期疾病，脊柱弯曲 不正常的。这种脊柱弯曲会导致虚弱的畸形和继发性的医疗问题。因此， EOSD是一个重要的儿科问题。脊柱侧弯为脊柱侧弯，脊柱侧弯为脊柱侧弯。 前向为后凸。EOSD可以通过手术治疗。有两种广泛使用的增长保留法 EOSD的手术方法：1)生长棒和2)VEPTR(垂直可膨胀钛肋骨)。 这些方法通过重新调整椎体提供了一些立即矫正脊柱畸形的方法，而且它们 可以通过随着时间的推移调节脊柱的生长来提供额外的逐渐矫正畸形。 然而，正如目前可用的那样，后凸过曲的存在使EOSD的手术治疗复杂化。 保留生长的内固定不能提供理想的矢状面畸形控制。此外， 在现有的手术入路中，后凸畸形增加了机械失败率。因此，一种新的外科手术 需要治疗后凸过度畸形的方法。我们正在开发一种新的方法，称为“肋骨结构”，它 利用一系列层状钩子将可伸缩的杆件固定在肋骨上。肋骨结构的优点是 在我们机构的一小部分患者身上和体外生物力学测试中进行了验证。 然而，到目前为止，还没有大规模的动物研究来检验这种行为和机制 在受控的实验室条件下矫正后凸畸形的肋骨结构。中心假说 这项建议的关键是肋骨结构将纠正儿童猪动物模型中的后凸过度畸形。 目的1将评估肋骨结构通过生长调节矫正儿童后凸畸形的能力。 猪的动物模型。我们将肋骨结构植入患有后凸畸形的幼猪体内，并评估其能力。 与标准的椎弓根螺钉治疗相比，矫正椎弓根弯曲。目标2将评估生物 肋骨结构在组织和细胞水平上调节脊柱生长的机制。我们将研究 肋骨构建的生物学机制是通过量化软骨细胞数量和密度以及 通过测量与软骨生成和成骨相关的标记基因和蛋白质的变化。目标3将 评估肋骨结构的生物力学性能。利用计算机模型模拟程序，我们将分析 测量内固定器械、骨和软组织的应力和应变分布，并与前两者进行比较。 传统的外科手术方法。我们将通过进行法向拔出力、弯曲、 以及人和猪身体脊柱的扭转生物力学测试。最后，我们将报告我们的临床 在一项对人类患者的回顾性研究中使用肋骨结构的数据。这个项目的成功可能会 革命性地治疗患有EOSD的儿童。通过提供骨科研究、基础生物学方面的培训 和工程科学，以及转化型医疗器械开发，该奖学金将促进发展 成为一名独特的整形外科学术临床医生/科学家。

Project Summary/Abstract Early-onset spinal deformity (EOSD) is a common affliction of early childhood in which the spine curves abnormally. This spinal curvature can induce debilitating deformity and secondary medical problems. Thus, EOSD is an important pediatric problem. Spinal deformity in the lateral direction is scoliosis, while deformity in the anterior direction is kyphosis. EOSD can be treated with surgery. There are two widely-used growth-sparing surgical methods for EOSD: 1) growing rods and 2) VEPTR (Vertical Expandable Prosthetic Titanium Rib). These methods provide some immediate correction of spinal deformity by realigning vertebral bodies, and they may provide additional gradual correction of the deformity via growth modulation of the spine over time. However, the presence of hyperkyphosis complicates the surgical treatment of EOSD, as currently available growth-sparing instrumentation does not provide ideal control of the deformity in the sagittal plane. Furthermore, hyperkyphosis increases mechanical failure rates in the existing surgical approaches. Thus, a new surgical method of treating hyperkyphosis is needed. We are developing a novel method, called the “rib construct,” which utilizes a series of laminar hooks to anchor extendable rods to the ribs. The merits of the rib construct have been validated anecdotally in a small series of patients and with ex vivo biomechanical testing at our institution. However, to date, there have been no large animal studies that have examined the performance and mechanism of the rib construct for correcting hyperkyphosis under controlled laboratory conditions. The central hypothesis of this proposal is that the rib construct will correct hyperkyphosis in a pediatric porcine animal model. Aim 1 will assess the ability of the rib construct to correct hyperkyphosis via growth modulation in a pediatric porcine animal model. We will implant the rib construct in juvenile pigs with hyperkyphosis and assess its ability to correct the curvature, compared to standard treatment with pedicle screws. Aim 2 will evaluate the biological mechanism of spinal growth modulation with the rib construct at the tissue and cellular level. We will examine the biological mechanism by which the rib construct works by quantifying chondrocyte number and density and by measuring changes in marker genes and proteins related to chondrogenesis and osteogenesis. Aim 3 will evaluate the biomechanics of the rib construct. Utilizing a computer model simulation program, we will analyze the stress and strain distributions on the instrumentation, bone, and soft tissues, then compare them to those of conventional surgical approaches. We will validate these findings by conducting normal pull-out force, bending, and torsional biomechanical testing on human and porcine cadaver spines. Finally, we will report our clinical data on the use of the rib construct in a retrospective study of human patients. Success in this project could revolutionize the treatment of children with EOSD. By providing training in orthopedic research, basic biological & engineering science, and translational medical device development, this fellowship will foster the development of the trainee into a unique orthopedic academic clinician/scientist.