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.

Public Health Relevance

Early-onset spinal deformity (EOSD) is an important pediatric problem. Currently available forms of surgical instrumentation fail to adequately control hyperkyphotic deformities in the sagittal plane and are plagued by high complication rates. The proposed studies will explore the safety, effectiveness, and mechanism of a novel type of instrumentation called the ?rib construct? to correct these deformities in a hyperkyphotic pediatric porcine animal model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AR076917-01A1
Application #
10068980
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Washabaugh, Charles H
Project Start
2020-07-09
Project End
2022-07-08
Budget Start
2020-07-09
Budget End
2021-07-08
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Pediatrics
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29407