Starting date ASAP
Position 1
"Mechanically driven cellular self-organization and soft tissue patterning in bone healing."
Background
Although bone is able to self-repair, in many situations its regeneration potential is impaired leading to delayed functional restoration or even non-unions. One of those situations concerns large bone defects which, if left untreated, results in limited bone tissue formation and unsuccessful healing. A peculiarity of this healing situation is that natural bone tissue patterning results in the formation of a bone capsule enclosing the medullary cavity. We have previously observed that this bone formation pattern follows collagen fiber organization that occurs much earlier during healing. The reason for this soft tissue patterning was found in cellular self-organization based on the traction forces generated by the individual cells. We have also observed that in large compared to small defects, there is a significant reduction in the levels of limb-loading induced mechanical strain under which the regeneration process takes place. Such local strains are also known to influence the structural organization of the tissue. However, it remains unknown to what extend both, traction force induced patterning and local mechanical strains within the healing region, interfere or synergistically contribute to soft tissue patterning with consequences for bone regeneration.
The aim of this project is to investigate how the two above-described mechanical aspects influence cellular and soft tissue organization representing different clinically relevant bone defect sizes. In particular, we will investigate how the mechanical/geometrical constrains in a large bone defect influence the spatial distribution of mechanical signals within the regenerating region and how those signals dictate cellular organization and soft tissue formation. We will also investigate potential ways to manipulate the mechanical environment of the healing region to influence cellular and tissue organization and prevent marrow encapsulation.
We will use an existing in vitro clamp setup to investigate cellular organization under controlled mechanical conditions which aim to replicate the physical/geometrical constrains in a large bone defect. Bioreactors will be used to apply in vivo-like cyclic mechanical loading signals and the influence of load magnitude and frequency on tissue patterning will be investigated. In vitro experiments will be coupled to computer models that determine the local mechanical strains surrounding individual cells and to better understand the dynamics of cellular self-organization and soft tissue formation under load.
Profile
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Position 2
"Multiscale Computer Modeling of Bone Regeneration."
Background
Although bone is able to self-repair after a fracture, in many situations its regeneration capacity is impaired, leading to delayed or non-unions, followed by expensive and painful secondary interventions. The unique process of bone healing is highly complex and dynamic and spans many different time and length scales. Processes at the intracellular, cellular and tissue scales are coordinated and interact to achieve bone restoration. At the intracellular level, a complex array of signalling molecules interact giving rise to the activation of specific genes which ultimately determine cell function. At the cellular level, cells proliferate, migrate, differentiate and synthesize extracellular matrix. At the tissue level bone, cartilage and fibrous tissue are organized providing the extracellular environment for the cells. Elucidating how the different processes interact between and within the different scales and how they are altered in impaired conditions might provide a unique opportunity in the design of clinical strategies for the treatment of bone fractures. Therefore, in this project we will develop and utilize multiscale computer models of bone healing to investigate the biological interactions taken place during bone regeneration and explore possible mechanisms leading to impaired conditions.
Profile
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As a PhD student you will be associated to the Berlin-Brandenburg School of Regenerative Therapies and benefit from the interaction with international students.
Starting date: as soon as possible.
Interested candidates should send a resume, a brief letter discussing future goals and fit for the position, and two references that could be contacted. Please email the application to Prof. Dr. Sara Checa (sara.checa@charite.de).
