Interaction of biological and mechanical stimuli during bone defect healing

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Identified the importance of the early inflammatory response to the mechanical induced bone regeneration

Despite the intrinsic ability of bone to heal, there are still numerous clinical circumstances where bone healing is defective. Common examples include the delayed and non-union of fractures, and the deficiency to heal large bone defects after trauma, tumor resection or failed arthroplasty. There are several surgical approaches to enhance the healing of human bones, and these have been supplemented in recent years by the introduction of recombinant, human bone morphogenetic proteins, BMP-2 or BMP-7, into clinical practice. Despite these improvements, the clinical management of critical-sized defects remains problematic.

Our project is based on the hypothesis that the healing of critical-sized defects in response to BMP-2 can be dramatically improved by manipulating the local mechanical environment within the defect. Accordingly, with this study we aim to determine whether the BMP-2 enhanced bone regeneration is sensitive to the local mechanical environment through a direct effect on BMPs signaling, or if it will be mediated by the mechanical factors on the production of key cytokines during the inflammatory phase. Moreover, we postulate that the disruption during this phase by mechanical stimuli will alter the initial immune response leading to changes of bone tissue repair through either the osteogenic or chondrogenic lineage. This will not only help us to understand the mechano-biological interplay in bone healing, but it will also have direct consequences on the fixation stability used in order to maximise the regenerative capacity of bone formation while minimising the dose of biological additives required in the clinical settings.