H2020Индивидуална стипендия2022–2024

MechanoHealing · Bone healing mechanomics in a mouse model of accelerated aging.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Механичните стимули влияят върху възстановяването на счупените кости, като например физическото натоварване може да ускори или забави процеса. Разбирането на тези механизми и промените им при стареенето помага за подобряване на лечението при трудни за заздравяване фрактури.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Bone healing mechanomics in a mouse model of accelerated aging.

In over 100 years, the remarkable ability of bone to adapt to its mechanical environment has been a source of scientific fascination. Bone adapts to its mechanical environment by forming bone at sites of mechanical loading and resorbing bone at sites of mechanical unloading. Multiple cell types are recognized to be mechano-sensitive and respond to mechanical stimuli through the activation of specific molecular signalling pathways. Fracture healing has been shown to be highly dependent on the mechanical environment at the fracture site. It has been demonstrated that mechanical stimuli can either accelerate or impede healing. Despite the fundamental importance of the mechanical environment in influencing fracture healing, the molecular mechanisms underlying this phenomenon are complex and poorly understood. This has prevented wider-scale harnessing of the mechano-sensitivity of the healing process in clinical applications. The use of mechanical intervention therapies to augment the healing response is of particular relevance in challenging fractures. Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures, presenting a significant challenge in regenerative medicine. Moreover, the prevalence of these challenging fractures is significantly greater in elderly populations. However, the field has yet to achieve consensus on whether bone exhibits age-associated declines in mechano-sensitivity. The objectives of this project were: (i) to develop a molecular-based understanding of bone healing mechanobiology and (ii) to investigate how this mechano-sensitivity is compromised with age.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures and present a challenging problem in regenerative medicine. Bone healing is a mechano-sensitive process; thus, mechanical stimuli can either enhance or impair fracture healing. The molecular mechanisms underlying this phenomenon are complex and poorly understood. Consequently, clinical applications which harness this mechano-sensitivity to enhance healing are limited. It has also contributed to a lack of consensus on whether bone exhibits age-associated declines in mechano-sensitivity. With this in mind, I present a multi-scale, multi-disciplinary approach to develop a molecular-based understanding of bone healing mechanobiology and to investigate how this mechano-sensitivity is compromised with age. Using an established femur defect model in young and aged mice, my proposed approach will apply state-of-the-art techniques to spatially map: (i) the local mechanical environment, (ii) the molecular profiles of single cells, and (iii) the local tissue nanostructure within the fracture callus. By combining single-cell “omics” technologies with established tissue-scale models of bone mechanobiology, MechanoHealing will quantify how mechanical stimuli are translated by individual cells and subcellular components to form bone. MechanoHealing will also permit investigations into potential pathways by which mechanical stimuli influence formation of the nanostructure of bone – a key determinant of the overall fracture resistance of bone. Identification of the molecular mechanisms of mechanically-driven bone formation will lead to new strategies and novel therapeutic targets to promote better and faster repair. Specifically, it will drive the development of safe, targeted and individualized mechanical intervention therapies. Furthermore, insights into age-associated declines in mechano-sensitivity will better equip surgeons to optimize outcomes in compromised healing environments.

Оригинален текст от CORDIS (на английски).

Участници

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichКоординаторШвейцария