Growth Plate Regeneration

描述(申请人提供)：生长板，也被称为骨骺板或生长板，是儿童和青少年长骨末端附近生长组织的区域，它决定了成熟骨未来的长度和形状。儿童长骨的软骨生长板骨折可能会导致生长停滞，随后出现腿长不等和进行性畸形。这种生长停滞是由于在创伤性生长板缺陷上形成了一根骨条，起到了抵抗进一步纵向生长的系绳作用。如果棒状物很大或位于生长板的中央部分，则会发生完全的生长停滞。位于生长板外围的一根杆不对称地束缚着生长，导致肢体的进行性角度畸形。一旦生长板形成，手术切除在技术上是困难的，而且进一步生长的恢复也是非常不稳定的。以往对实验性生长板损伤的研究主要集中在生长板缺损处的组织学事件，导致条状结构的形成。然而，在过去的十年里，我们对调控生长板软骨细胞增殖和分化的因素以及软骨组织工程的原理的了解有了很大的提高。这些进展为严重生长板损伤后正常生长板软骨的再生提供了独特的机会。生长板软骨结构在体内的成功再生将对儿科整形外科的实践产生变革性的影响，不仅首次提供了替换因创伤、感染或辐射而不可逆转地损坏的生长板的能力，而且提供了在超过骨骼成熟年龄后恢复个体纵向生长的可能性。我们的假设是，将共培养的软骨细胞和成骨细胞植入体内的胫骨缺损区，将重现正常生长板的功能，并导致柱状生长板结构的改变和纵向生长的恢复。这一假设将通过使用组织工程学方法来验证，以确定在植入完全生长板缺陷后，这种优化的生长板结构在多大程度上复制了体内正常生长板的功能。

DESCRIPTION (provided by applicant): The growth plate, also known as the epiphyseal plate or physis, is the area of growing tissue near the end of the long bones in children and adolescents that determines the future length and shape of the mature bone. Fractures through the cartilage growth plates of the long bones of children may result in growth arrest with subsequent leg length inequality and progressive deformity. This growth arrest is due to formation of a bony bar across the traumatic growth plate defect that acts as an tether to resist further longitudinal growth. If the bar is large or is located in the central portion of the growth plate, a complete growth arrest ensues. A bar located in the peripheral portion of the physis tethers growth asymmetrically, producing a progressive angular deformity of the limb. Once a physeal bar forms, surgical excision is technically difficult and resumption of further growth is quite variable. Previous studies of experimental growth plate injury have focused on the histological events in the growth plate defect leading to bar formation. However, our understanding of the factors that regulate the proliferation and differentiation of growth plate chondrocytes, as well as the principles of cartilage tissue engineering, have increased dramatically over the past decade. These advances now provide a unique opportunity to develop strategies for regeneration of normal physeal cartilage following serious growth plate injuries. Successful regeneration of growth plate cartilage architecture in vivo would have a transformational impact on the practice of pediatric orthopaedic surgery, providing for the first time not only the ability to replace growth plates irreversibly damaged by trauma, infection or irradiation, but also the possibility of restoring longitudinal growth in individuals beyond the age of skeletal maturity. Our hypothesis is that co-cultured chondrocytes and osteoblasts implanted into tibial bone defects in vivo will recapitulate the function of the normal growth plate and result in the reformation of columnar physeal architecture and resumption of longitudinal growth. This hypothesis will be tested by using a tissue engineering approach to determine the degree to which this optimized physeal construct replicates the function of the normal growth plate in vivo following implantation into a complete growth plate defect.