There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relationship between an individual's immune reactivity and healing outcome. Our study revealed that delayed fracture healing significantly correlated with enhanced levels of terminally differentiated CD8(+) effector memory T (TEMRA) cells (CD3(+)CD8(+)CD11a(++)CD28(-)CD57(+) T cells) in peripheral blood. This difference was long lasting, reflecting rather the individual's immune profile in response to lifelong antigen exposure than a post-fracture reaction. Moreover, CD8(+) TEMRA cells were enriched in fracture hematoma; these cells were the major producers of interferon-γ/tumor necrosis factor-α, which inhibit osteogenic differentiation and survival of human mesenchymal stromal cells. Accordingly, depletion of CD8(+) T cells in a mouse osteotomy model resulted in enhanced endogenous fracture regeneration, whereas a transfer of CD8(+) T cells impaired the healing process. Our data demonstrate the high impact of the individual adaptive immune profile on endogenous bone regeneration. Quantification of CD8(+) TEMRA cells represents a potential marker for the prognosis of the healing outcome and opens new opportunities for early and targeted intervention strategies.

Combined knowledge of the functional kinematics and kinetics of the human body is critical for understanding a wide range of biomechanical processes including musculoskeletal adaptation, injury mechanics, and orthopaedic treatment outcome, but also for validation of musculoskeletal models. Until now, however, no datasets that include internal loading conditions (kinetics), synchronized with advanced kinematic analyses in multiple subjects have been available. Our goal was to provide such datasets and thereby foster a new understanding of how in vivo knee joint movement and contact forces are interlinked - and thereby impact biomechanical interpretation of any new knee replacement design. In this collaborative study, we have created unique kinematic and kinetic datasets of the lower limb musculoskeletal system for worldwide dissemination by assessing a unique cohort of 6 subjects with instrumented knee implants (Charité - Universitätsmedizin Berlin) synchronized with a moving fluoroscope (ETH Zürich) and other measurement techniques (including whole body kinematics, ground reaction forces, video data, and electromyography data) for multiple complete cycles of 5 activities of daily living. Maximal tibio-femoral joint contact forces during walking (mean peak 2.74 BW), sit-to-stand (2.73 BW), stand-to-sit (2.57 BW), squats (2.64 BW), stair descent (3.38 BW), and ramp descent (3.39 BW) were observed. Internal rotation of the tibia ranged from 3° external to 9.3° internal. The greatest range of anterio-posterior translation was measured during stair descent (medial 9.3 ± 1.0 mm, lateral 7.5 ± 1.6 mm), and the lowest during stand-to-sit (medial 4.5 ± 1.1 mm, lateral 3.7 ± 1.4 mm). The complete and comprehensive datasets will soon be made available online for public use in biomechanical and orthopaedic research and development.

BackgroundThe onset and progression of osteoarthritis, but also the wear and loosening of the components of an artificial joint, are commonly associated with mechanical overloading of the structures. Knowledge of the mechanical forces acting at the joints, together with an understanding of the key factors that can alter them, are critical to develop effective treatments for restoring joint function. While static anatomy is usually the clinical focus, less is known about the impact of dynamic factors, such as individual muscle recruitment, on joint contact forces.MethodsIn this study, instrumented knee implants provided accurate in vivo tibio-femoral contact forces in a unique cohort of 9 patients, which were used as input for subject specific musculoskeletal models, to quantify the individual muscle forces during walking and stair negotiation.ResultsEven between patients with a very similar self-selected gait speed, the total tibio-femoral peak forces varied 1.7-fold, but had only weak correlation with static alignment (varus/valgus). In some patients, muscle co-contraction of quadriceps and gastrocnemii during walking added up to 1 bodyweight (~ 50%) to the peak tibio-femoral contact force during late stance. The greatest impact of co-contraction was observed in the late stance phase of stair ascent, with an increase of the peak tibio-femoral contact force by up to 1.7 bodyweight (66%).ConclusionsTreatment of diseased and failed joints should therefore not only be restricted to anatomical reconstruction of static limb axes alignment. The dynamic activation of muscles, as a key modifier of lower limb biomechanics, should also be taken into account and thus also represents a promising target for restoring function, patient mobility, and preventing future joint failure.Trial registrationGerman Clinical Trials Register: ID: DRKS00000606, date: 05.11.2010.Electronic supplementary materialThe online version of this article (10.1186/s12984-018-0434-3) contains supplementary material, which is available to authorized users.