The investigation of tendon ECM alterations in response to stress relaxation for improving the Ponseti method

Congenital clubfoot or congenital talipes equinovarus (CTEV) is a complex paediatric foot deformity which will lead to long-term disability, deformity, and pain if left untreated. At present, the Ponseti method composed of a series of manipulation and casting is recognized as the standard treatment...

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Autor principal: Lee, MH
Altres autors: Czernuszka, J
Format: Thesis
Idioma:English
Publicat: 2022
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Sumari:Congenital clubfoot or congenital talipes equinovarus (CTEV) is a complex paediatric foot deformity which will lead to long-term disability, deformity, and pain if left untreated. At present, the Ponseti method composed of a series of manipulation and casting is recognized as the standard treatment for clubfoot. However, the evaluation for the treatment outcome is based primarily on the clinical examinations and functional parameters while no work has explored the material response and the alterations of extracellular matrix (ECM) of a clubfoot tendon in response to the treatment – a long term stress relaxation. Ex vivo stress relaxation experiments discovered time-dependent tendon lengthening and ECM alterations including crimp angle reduction and elastin fragmentation, which illustrated the mechanism behind the treatment – a material-based tissue lengthening resulted from elastin fragmentation. This proposed mechanism was further supported by the relaxation results using elastin-digested tendons which also found a positive contribution to stress relaxation and relaxation rate from elastin. As the changes in crimp and elastin structures will be influential in the function and health of the tendon tissue, the capability of recovery of these ECM alterations in a tendon became a critical examination. The in vivo results derived from stress-relaxed tendons of young rabbits observed restoration of the above-mentioned ECM alterations along with increased elastin and vascularity level, and the existence of inflammation, indicating process of healing and recovery from the tendon in reaction to the treatment over time. While the increased vascularity and persisted inflammation may potentially bring concerns to the tendon health, they are both important biological adaptation in response to the mechanical treatment. Additionally, cellular response derived from the in vitro experiment discovered increased gene expressions of COL1A1 and ELN, supporting the incidence of recovery. Overall, this study reveals the treatment mechanism and proves the efficacy of the Ponseti method to correct clubfoot from an ECM-oriented perspective.