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Ausgewählte Publikationen

  • Köhli P, Appelt J, Otto E, Jahn D, Baranowsky A, Bahn A, Erdmann C, Müchler J, Mülleder M, Tsitsilonis S, Keller J

    Effects of CGRP receptor antagonism on glucose and bone metabolism in mice with diet-induced obesity

    Our study was designed to characterize the effects of CGRP antagonism on bone and glucose metabolism in a murine model of diet-induced obesity (DIO). A subcutaneous pellet releasing the CGRP receptor antagonist BIBN 4096 (BIBN; olcegepant) was implanted in WT mice with DIO. Metabolic effects were assessed through body- and organ-weights, oral glucose tolerance (oGT), serum lipids, and gene-expression studies. Bone turnover was assessed through histomorphometry of non-decalcified bone sections and analyses of bone turnover markers in serum samples. BIBN treatment did not alter body weight gain or the levels of serum lipids including triacylglycerol and cholesterol during DIO. BIBN led to a moderate improvement of oGT which was accompanied by an increased expression of stearoyl-CoA desaturase in the liver. In skeletal tissue, BIBN treatment resulted in reduced bone volume. This was explained by decreased parameters of bone formation whereas bone resorption was not affected.

    Bone 2021; 143

  • Borcherding K, Marx D, Gätjen L, Specht U, Salz D, Thiel K, Wildemann B, Grunwald I

    Impact of Laser Structuring on Medical-Grade Titanium: Surface Characterization and In Vitro Evaluation of Osteoblast Attachment

    A laser treatment to structure standard titanium alloy implants for improved osteointegration offers meaningful potential for orthopedic implants. The objective of this study was to characterize the pore structure shape, treatment‐related metallographic changes, cytocompatibility, and attachment of osteoblast‐like cells (MG‐63).The pore dimensions were a bottleneck diameter of 27 μm, an inner pore width of 78 μm, and a pore depth of 129 μm. The introduced energy of the laser changed the metallic structure of the alloy within the heat‐affected region (approximately 66 μm) without any indication of a micro cracking formation. Cell viability was improved on the structured surface compared to pure titanium, indicating good cytocompatibility.

    Materials (Basel) 2020; 13(8)

  • Fleischhacker V, Klatte-Schulz F, Minkwitz S, Schmock A, Rummler M, Seliger A, Willie BM, Wildemann B

    In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes-A Pilot Study

    Mechanical force is a key factor for the maintenance, adaptation, and function of tendons. Investigating the impact of mechanical loading in tenocytes and tendons might provide important information on in vivo tendon mechanobiology. Therefore, the study aimed at understanding if an in vitro loading set up of tenocytes leads to similar regulations of cell shape and gene expression, as loading of the Achilles tendon in an in vivo mouse model. This study showed that the gene expression of tendon markers was similar, whereas significant changes in cell shape and the expression of extracellular matrix (ECM) related genes were detected between in vivo and in vitro loading.
    This first pilot study is important for understanding to which extent in vitro stimulation set-ups of tenocytes can mimic in vivo characteristics.

    Int J Mol Sci 2020; 21(4)

  • Schlundt C, Reinke S, Geissler S, Bucher CH, Giannini C, Märdian S, Dahne M, Kleber C, Samans B, Baron U, Duda GN, Volk HD, Schmidt-Bleek K

    Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration

    There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration Using adoptive TReg transfer, bone healing was consistently improved in mice possessing an inexperienced immune system with low amounts of CD8+ TEFF. In contrast, mice with an experienced immune system (high amounts of CD8+ TEFF) showed heterogeneous bone repair with regeneration being dependent upon the individual TEFF/TReg ratio. Thus, the healing outcome can only be improved by an adoptive TReg therapy, if an unfavorable TEFF/TReg ratio can be reshaped; if the individual CD8+ TEFF percentage, which is dependent on the individual immune experience can be changed toward a favorable ratio by the TReg transfer.

    Front Immunol 2019; 10

  • Bucher C, Schlundt C, Wulsten D, Sass F, Wendler S, Ellinghaus A, Thiele T, Seemann R, Willie B, Volk H, Duda G, Schmidt-Bleek K

    Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing

    Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Bone formation is impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. Considering the immune system's experience level will likely allow a more effective differentiation (stratify) and treatment (immune-modulate) of patients .

    Front Immunol 2019; 10:797.

  • Borgiani E, Figge C, Kruck B, Willie BM, Duda GN, Checa S

    Age-related changes in the mechanical regulation of bone healing are explained by altered cellular mechanoresponse

    We used a combined in vivo/in silico approach to investigate age-related alterations in the mechanical regulation of bone healing and identified the relative impact of altered cellular function on tissue patterns during the regenerative cascade. To modulate the mechanical environment, femoral osteotomies in adult and elderly mice were stabilized using either a rigid or a semirigid external fixator and the course of healing was evaluated using histomorphometric and microCT analyses at 7, 14 and 21 days post-surgery. Computer models were developed to investigate the influence of the local mechanical environment within the callus on tissue formation patterns.

    J Bone Miner Res 2019; doi: 10.1002/jbmr.3801

  • Cilla M, Borgiani E, Martinez J, Duda GN, Checa S

    Machine learning techniques for the optimization of joint replacements: Application to a short-stem hip implant

    The aim of this project was to investigate if the geometry of a commercial short stem hip prosthesis can be further optimized to reduce stress shielding effects and achieve better short-stemmed implant performance. To reach this aim, the potential of machine learning techniques combined with parametric Finite Element analysis was used. The selected implant geometrical parameters were: total stem length (L), thickness in the lateral (R1) and medial (R2) and the distance between the implant neck and the central stem surface (D). The results show that the total stem length was not the only parameter playing a role in stress shielding. An optimized implant should aim for a decreased stem length and a reduced length of the surface in contact with the bone.

    PLoS One 2017; 12(9):e0183755.

  • Agres AN, Chrysanthou M, Raffalt PC

    The Effect of Ankle Bracing on Kinematics in Simulated Sprain and Drop Landings: A Double-Blind, Placebo-Controlled Study.

    The efficacy of external ankle braces to protect against sudden inversion sprain has yet to be determined while taking into account the possible placebo effect of brace application. To assess the protective effect of an external ankle brace on ankle kinematics during simulated inversion sprain and single-legged drop landings among individuals with a history of unilateral lateral ankle sprain. The primary hypothesis was that active and placebo external braces would reduce inversion angle during simulated inversion sprain. Sixteen participants with ankle instability and previous sprain performed single-legged drop landings and sudden inversion tilt perturbations. Kinematics of the affected limb were assessed in 3 conditions (active bracing, passive placebo bracing, and unbraced) across 2 measurement days. Participators and investigators were blinded to the brace type tested. The effect of bracing on kinematics was assessed with repeated measures analysis of variance with statistical parametric mapping, with post hoc tests performed for significant interactions. Only active bracing reduced inversion angles during a sudden ankle inversion when compared with the unbraced condition. This reduction was apparent between 65 and 140 milliseconds after the initial fall. No significant differences in inversion angle were found between the passive placebo brace and unbraced conditions during sudden ankle inversion. Furthermore, no significant differences were found among all tested conditions in the sagittal plane kinematics at the knee and ankle. During an inversion sprain, only the actively protecting ankle brace limited inversion angles among participants. These results do not indicate a placebo effect of external bracing for patients with ankle instability and a history of unilateral ankle sprain. Furthermore, sagittal plane knee kinematics appear to remain unaffected by bracing during single-legged landing, owing to the limited effects of bracing on sagittal ankle kinematics. These results highlight the role of brace design on biomechanical function during sports-related and injury-prone movements.

    Am J Sports Med 2019; 47(6):1480-1487.

  • Trepczynski A, Kutzner I, Schutz P, Dymke J, List R, von Roth P, Moewis P, Bergmann G, Taylor WR, Duda GN

    Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty

    Total knee arthroplasty aims to mimic the natural knee kinematics by optimizing implant geometry, but it is not clear how loading relates to tibio-femoral anterior-posterior translation or internal-external pivoting. Tibio-femoral loading was measured using an instrumented tibial component in six total knee arthroplasty patients (aged 65-80y, 5-7y post-op) during 5-6 squat repetitions, while knee kinematics were captured using a mobile video-fluoroscope. In the range of congruent tibio-femoral contact the medial femoral condyle remained approximately static while the lateral condyle translated posteriorly by 4.1 mm (median). Beyond the congruent range, the medial and lateral condyle motions both abruptly changed to anterior sliding by 4.6 mm, and 2.6 mm respectively. On average, both the axial loading and pivot position were more medial near extension, and transferred to the lateral side in flexion. However, no consistent relationship between pivoting and load distribution was found across all patients throughout flexion, with R(2) values ranging from 0.00 to 0.65. Tibio-femoral kinematics is not related to the load distribution alone: medial loading of the knee does not necessarily imply a medial pivot location.

    Sci Rep 2019; 9(1):182.

  • Qazi TH, Duda GN, Ort MJ, Perka C, Geissler S, Winkler T

    Cell therapy to improve regeneration of skeletal muscle injuries

    Traumatic muscle injuries represent a heterogeneous spectrum of causes, severity, and intervention options. A common feature of severe muscle injuries is the pathological observation of haematoma, muscle atrophy, fibrotic scar tissue, and fatty infiltration, with associated physical disabilities like functional impairment, limping, soreness, and pain. These pathological features have been replicated in small animal injury models using various approaches and techniques. Cell therapies using MSCs, myoblasts, or MDSCs have shown apparent benefit in pre‐clinical settings, and some have been tested in human clinical trials with promising outcomes. Although few in number, these clinical studies demonstrate the potential to accelerate and significantly improve the healing of traumatic muscle injuries through autologous or allogeneic cell‐based solutions.

    J Cachexia Sarcopenia Muscle 2019; 10(3):501-502.

  • Andrzejewska A, Catar R, Schoon J, Qazi TH, Sass FA, Jacobi D, Blankenstein A, Reinke S, Krüger D, Streitz M, Schlickeiser S, Richter S, Souidi N, Beez C, Kamhieh-Milz J, Krüger U, Zemojtel T, Jürchott K, Strunk D, Reinke P, Duda G, Moll G, Geissler S

    Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

    Currently, it is unclear whether advanced donor age and commonly associated comorbidities affect the properties of ex vivo-expanded BMSCs. Here, we stratified cells from adult and elderly donors from our biobank and compared their phenotypic and functional performance, using multiple assays typically employed as minimal criteria for defining multipotent mesenchymal stromal cells (MSCs). We found that BMSCs from both cohorts meet the standard criteria for MSC, exhibiting similar molecular, cellular, and functional morphology, growth kinetics, gene expression profiles, and pro-angiogenic and immunosuppressive potential and the capacity to differentiate toward adipogenic, chondrogenic, and osteogenic lineages. We conclude that in vitro culture rather than in vivo donor aging influences BMSC characteristics.

    Front Immunol 2019; 10

  • Qazi TH, Mooney DJ, Duda GN, Geissler S

    Niche-mimicking interactions in peptide-functionalized 3D hydrogels amplify mesenchymal stromal cell paracrine effects

    Here, we show that 3D culture in microporous hydrogels that passively promote cell-cell interactions sensitizes MSCs to growth factors, particularly to IGF-1. IGF-1 enhances MSC paracrine secretion activity, and application of secreted factors to myoblasts potently stimulates their migration and differentiation. In contrast, the paracrine activity of MSCs encapsulated in nanoporous (~10 nm) hydrogels remain unchanged. Blocking N-cadherin on MSCs abrogates the stimulatory effects of IGF-1 in microporous but not nanoporous hydrogels. The role of N-cadherin in regulating MSC function is further clarified by functionalizing alginates with the HAVDI peptide sequence that is derived from the extracellular domain of N-cadherin and that acts to mimic cell-cell interactions. MSCs encapsulated in nanoporous HAVDI-gels, but not in gels functionalized with a scrambled sequence, show heightened paracrine activity in response to IGF-1. These findings reveal how interactions with the matrix, neighboring cells, and soluble factors impact and maximize the regenerative potential of MSCs.

    Biomaterials 2020; 230