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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR061265-01A1
Application #
8258573
Study Section
Special Emphasis Panel (ZRG1-MOSS-S (02))
Program Officer
Tyree, Bernadette
Project Start
2012-04-11
Project End
2014-03-31
Budget Start
2012-04-11
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$157,000
Indirect Cost
$57,000
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
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