Growth Plate Regeneration

描述（由申请人提供）：生长板，也称为骺板或骺板，是儿童和青少年长骨末端附近的生长组织区域，决定了成熟骨的未来长度和形状。儿童长骨的软骨生长板骨折可能导致生长停滞，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损处形成了一个骨条，它作为一个系绳来阻止进一步的纵向生长。如果生长棒很大或位于生长板的中心部分，则完全生长停滞。位于骺板栓系的周边部分的杆不对称地生长，产生肢体的进行性成角畸形。一旦骨骺棒形成，手术切除在技术上是困难的，并且恢复进一步生长是相当可变的。 以往的实验性生长板损伤的研究主要集中在生长板缺损导致生长条形成的组织学事件上。然而，我们对生长板软骨细胞增殖和分化的调节因素以及软骨组织工程原理的理解在过去十年中急剧增加。这些进展现在提供了一个独特的机会，发展战略，正常骺软骨严重生长板损伤后的再生。 生长板软骨结构在体内的成功再生将对儿科骨科手术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地受损的生长板的能力，而且还提供了在骨骼成熟年龄之后恢复个体纵向生长的可能性。 我们的假设是，软骨细胞和成骨细胞共培养植入胫骨骨缺损体内将重演正常生长板的功能，导致柱状骨骺结构的重建和纵向生长的恢复。将通过使用组织工程方法来测试该假设，以确定该优化的骨骺结构在植入完全生长板缺损后在体内复制正常生长板功能的程度。 公共卫生相关性：在过去的十年中，我们对生长板软骨细胞增殖和分化的调节因素以及软骨组织工程原理的理解急剧增加。这些进展现在提供了一个独特的机会，发展战略的正常骺板软骨生长板损伤后的再生。生长板软骨结构在体内的成功再生将对儿科骨科手术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地受损的生长板的能力，而且还提供了在骨骼成熟年龄之后恢复个体纵向生长的可能性。

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. PUBLIC HEALTH RELEVANCE: 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 growth plate injury. 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.