Growth Plate Regeneration

描述（由申请人提供）：生长板，也称为骨骺板或骨骺，是儿童和青少年长骨末端附近的生长组织区域，决定未来成熟骨的长度和形状。通过儿童长骨软骨生长板的骨折可能导致生长停滞，随之而来的腿长不均匀和进行性畸形。这种生长停滞是由于在创伤性生长板缺陷上形成骨棒，作为一种绳索来阻止进一步的纵向生长。如果棒材很大或位于生长板的中心部分，则会发生完全的生长停滞。位于身体外围部分的一根杆状物不对称地生长，产生肢体的进行性角状畸形。一旦骨骺块形成，手术切除在技术上是困难的，恢复进一步生长的情况也很不稳定。以往对生长板损伤的研究主要集中在生长板缺损导致棒状形成的组织学事件上。然而，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。这些进展为发展严重生长板损伤后正常骨骺软骨再生策略提供了独特的机会。体内生长板软骨结构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、感染或辐照而不可逆转损伤的生长板的能力，而且还提供了恢复骨骼成熟年龄以上个体纵向生长的可能性。我们的假设是，将共培养软骨细胞和成骨细胞植入体内胫骨骨缺损，将重现正常生长板的功能，并导致柱状骨骺结构的改造和纵向生长的恢复。这一假设将通过使用组织工程方法进行验证，以确定在植入完整的生长板缺陷后，这种优化的物理结构在体内复制正常生长板功能的程度。

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.