Kurth F.,ETH Zurich |
Franco-Obregon A.,National University Hospital Singapore |
Franco-Obregon A.,National University of Singapore |
Casarosa M.,Institute for Biomechanics |
And 2 more authors.
FASEB Journal | Year: 2015
The developmental sensitivity of skeletal muscle to mechanical forces is unparalleled in other tissues. Calcium entry via reputedly mechanosensitive transient receptor potential (TRP) channel classes has been shown to play an essential role in both the early proliferative stage and subsequent differentiation of skeletal muscle myoblasts, particularly TRP canonical (TRPC) 1 and TRP vanilloid (TRPV) 2. Here we show that C2C12 murine myoblasts respond to fluid flow-induced shear stress with increments in cytosolic calcium that are largely initiated by the mechanosensitive opening of TRPV2 channels.Response to fluid flowwas augmented by growth in low extracellular serum concentration (5 vs. 20% fetal bovine serum) by greater than 9-fold and at 18 h in culture, coincident with the greatest TRPV2 channel expression under identical conditions (P < 0.02). Fluid flow responses were also enhanced by substrate functionalization with laminin, rather than with fibronectin, agreeing with previous findings that the gating of TRPV2 is facilitated by laminin. Fluid flow-induced calcium increments were blocked by ruthenium red (27%) and SKF-96365 (38%), whereas they were unaltered by 2-aminoethoxydiphenyl borate, further corroborating that TRPV2 channels play a predominant role in fluid flow mechanosensitivity over that ofTRPC1 andTRPmelastatin (TRPM) 7.-Kurth, F., Franco-Obregón, A., Casarosa, M., Küster, S. K., Wuertz-Kozak, K., Dittrich, P. S. Transient receptor potential vanilloid 2-mediated shear-stress responses in C2C12 myoblasts are regulated by serum and extracellular matrix. © FASEB.
Lehner C.,Paracelsus Medical University |
Gehwolf R.,Paracelsus Medical University |
Hirzinger C.,Paracelsus Medical University |
Stephan D.,Institute for Biomechanics |
And 8 more authors.
American Journal of Sports Medicine | Year: 2013
Background: Toxicity of the local anesthetic bupivacaine (BV) has been a matter of debate across medical fields. Numerous in vitro studies demonstrate considerable toxicity of BV on various cell types. Purpose: This study addresses the question of how tendon tissue responds to BV in vivo and in vitro. Study Design: Controlled laboratory study. Methods: In vitro studies on cultured rat Achilles tendon-derived cells were performed with cell viability assays and cleaved caspase 3 immunocytochemistry. Quantitative reverse transcription- polymerase chain reaction, Western blotting, gelatin zymography, and a biomechanical testing routine were applied on rat Achilles tendons at 1 and 4 weeks after a single unilateral peritendinous injection of 0.5% BV. The BV-mediated cell death in tendons was estimated with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and immunohistochemical detection of cleaved caspase 3. Results: Treatment of rat tendon-derived cells with 0.5% bupivacaine for 10 minutes had detrimental effects on cell viability, which can be reduced by N-acetyl-L-cysteine or reduction of extracellular calcium. In vivo, single peritendinous injections of BV caused apoptosis in endotenon cells and an increase of pro-matrix metalloproteinase-9 after 6 hours. The collagen ratio shifted toward collagen type III after 6 hours and 2 days; scleraxis messenger RNA (mRNA) expression was reduced by 87%. Maximum tensile load was reduced by 17.6% after 1 week. Conclusion: Bupivacaine exerts a severe, reactive oxygen species-mediated effect on tendon cell viability in vitro in a time- and dose-dependent manner, depending on extracellular calcium concentration. Culture conditions need to be taken into account when in vitro data are translated into the in vivo situation. In vivo, administration of BV elicits a marked but temporary functional damage. Clinical Relevance: Local anesthetics cause short-term alterations in rat tendons, which, if occurring in humans to a similar extent, may be relevant regarding decreased biomechanical properties and increased vulnerability to tendon overload or injury. © 2013 The Author(s).
Augat P.,Institute for Biomechanics |
Weyand D.,Institute for Biomechanics |
Panzer S.,Trauma Center Murnau |
Klier T.,Trauma Center Murnau
Archives of Orthopaedic and Trauma Surgery | Year: 2010
Purpose: The aim of this study was to characterize the features of fractures that occur in female patients with osteoporosis in the setting of a typical trauma hospital. Methods: Observational study was conducted on 233 women aged 50 years and above reporting to a trauma center with a fracture. Fracture location, fracture classification and cause of fracture were obtained and compared with bone mineral status assessed by DXA at the spine. Results: Our findings indicate that with increasing patient age, the majority of fractures occur after a minor traumatic event. In more than one-third of all fractures after minor trauma, the patients were diagnosed with osteoporosis. The overall prevalence of osteoporosis in patients older than 50 years with fractures was more than 30% and was increasing with age. Most strikingly, one-third of the patients have had a previous fracture at a location that should have triggered the assessment of bone health status, but only 25% of them had received any form of osteoporosis treatment. Conclusion: For patients older than 50 years reporting to a trauma unit with a fracture, osteoporosis has a considerable prevalence. The large number of patients who have had a previous fracture emphasizes the necessity for an effective implementation of treatment algorithms for elderly patients with osteoporosis in the setting of a trauma hospital. © 2010 Springer-Verlag.
Hogel F.,Institute for Biomechanics |
Hoffmann S.,Institute for Biomechanics |
Panzer S.,BG Unfallklinik Murnau E.V. |
Wimber J.,Aesculap AG |
And 2 more authors.
Archives of Orthopaedic and Trauma Surgery | Year: 2013
Background: Fractures of the proximal tibia occur very often and are a great challenge for trauma surgeons to stabilize. Although locked nails were developed to stabilize these fractures, this technique has not been sufficiently investigated. The purpose of this study was to biomechanically assess the stability of locked intramedullary nailing compared to locked plating. Methods: 16 fresh frozen human cadaveric tibiae were osteotomized in the meta-diaphyseal intersection with an osteotomy gap of 10 mm and a single osteotomy through the medial epicondyle to simulate a 41-C.2 fracture. Stabilization was performed with an angle stable locked Targon-TX nail (n = 8) and two additional canulated screws. The other testing group (n = 8) was treated with two canulated screws and a five-hole LCP-PLT. The bones were tested in a cyclic testing protocol with increasing loads under compression and a load sharing of 60 % through the medial tibial plateau and 40 % to the lateral side. Stiffness and fracture gap movement were measured and failure mode was assessed. Results: No significant differences were found between the two implants regarding load until failure. The stiffness of the intramedullary nailing group (927 N/mm) was statistically significantly higher than the stiffness of the plating group (564 N/mm). No differences were found for fracture gap movement in the z-axis. However, differences were found for dislocation of the proximal-lateral and proximal-medial fragments, with absolute values of 0.099 mm in the plate group and 0.66 mm in the nailing group at 800 N. Prior to failure, fracture gap movement was 0.22 mm for the plating group and 1.66 mm for the nailing group, a difference that was also statistically significantly different. The nailing group failed by screw cut-out while the plating group failed by screw breakage. Conclusion: Nailing of proximal tibia fractures leads to a stiffer implant-bone construct than plating. Since no adverse effects were found after nailing it seems to be a good alternative to plating for intra-articular proximal tibia fractures, especially in patients with soft tissue problems. © 2012 Springer-Verlag Berlin Heidelberg.
Hagenmuller H.,ETH Zurich |
Hitz M.,ETH Zurich |
Merkle H.P.,ETH Zurich |
Meinel L.,ETH Zurich |
And 3 more authors.
Review of Scientific Instruments | Year: 2010
Mechanical loading plays an important role in bone remodeling in vivo and, therefore, has been suggested as a key parameter in stem cell-based engineering of bone-like tissue in vitro. However, the optimization of loading protocols during stem cell differentiation and subsequent bone-like tissue formation is challenged by multiple input factors, which are difficult to control and validate. These include the variable cellular performance of cells harvested from different patients, nonstandardized culture media components, the choice of the biomaterial forming the scaffold, and its morphology, impacting a broader validity of mechanical stimulation regimens. To standardize the cell culture of bone-like tissue constructs, we suggest the involvement of time-lapsed feedback loops. For this purpose we present a prototype bioreactor that combines online, nondestructive monitoring using micro-computed tomography and direct mechanical loading of three-dimensional tissue engineering constructs. Validation of this system showed displacement steps down to 1 μm and cyclic sinusoidal loadings of up to 10 Hz. Load detection resolution was 0.01 N, and micro-computed tomography data were of high quality. For the first time, the developed bioreactor links time-lapsed, nondestructive, and dynamic imaging with mechanical stimulation, designed for cell culture under sterile conditions. This system is believed to substantially improve today's experimental options to study and optimize osteogenic stem cell culture and differentiation at the interface with mechanical stimulation. © 2010 American Institute of Physics.
Hogel F.,Berufsgenossenschaftliche Unfallklinik Murnau |
Hogel F.,Institute for Biomechnics |
Mair S.,Institute for Biomechnics |
Mair S.,Institute for Biomechanics |
And 6 more authors.
Archives of Orthopaedic and Trauma Surgery | Year: 2013
Background: Fractures of the distal radius represent the most common fractures in adults. Volar locked plating has become a popular method for treating these fractures, but has been subject to several shortcomings in osteoporotic bone, such as loss of reduction and screw purchase. In order to overcome these shortcomings, cement augmentation has been proposed. Methods: AO-type 23-A3.3 fractures were made in 8 pairs of fresh frozen osteoporotic cadaveric radial bones. All specimens were treated with volar plating, and divided into cement augmentation or non-augmentation groups (n = 8/group). Constructs were tested dynamically and load to failure, construct-stiffness, fracture gap movement and screw cutting distance were measured. Results: Cement augmentation resulted in a significant increase in cycles and load to failure, as well as construct stiffness at loads higher than 325 N. When compared to the non-augmented group, fracture gap movement decreased significantly at this load and higher, as did screw cutting distance at the holes of the ulnar column. The cycles to failure depend on the BMD in the distal region of the radius. Conclusion: Cement augmentation improves biomechanical properties in volar plating of the distal radius. © 2012 Springer-Verlag Berlin Heidelberg.
Hogel F.,Institute for Biomechanics |
Hogel F.,Traumacenter Murnau e.V. |
Gerber C.,Stryker Osteosynthesis |
Buhren V.,Traumacenter Murnau e.V. |
And 2 more authors.
European Journal of Trauma and Emergency Surgery | Year: 2013
Background: Modern intramedullary implants provide the option to perform compression at the fracture gap in long bone fractures via a compression screw mechanism. The aim of this study was to assess if the application of interfragmentary compression in the intramedullary nailing of tibia fractures could increase the union rate and speed of fracture healing. Methods: Sixty-three patients who suffered from an AO-type 42-A3 or 42-B2 fracture that was treated by reamed intramedullary nailing between 2003 and 2008 were included in this retrospective study. Twenty-five patients were treated with dynamic interlocking without compression while 38 were treated with compression nailing. The compression load of the dynamic proximal screw was calculated by postoperative X-ray and radiographs taken four weeks after operation. Healing was assessed by radiological evaluation until the completion of bony healing or the disappearance of clinical symptoms. Nonunion was defined as the absence of radiological union and the persistence of clinical symptoms after six months. Results: Postoperative compression was applied at a mean load of 1,852 N, and 980 N remained after four weeks. In the compression group, 19 open and 19 closed fractures occurred. In the non-compression group, 25 patients were included (14 closed and 11 open cases). Active compression decreased healing time significantly. Nonunion occurred in one compression patient and three non-compression patients. Conclusion: The results show that additional compression of the fracture gap can improve healing outcome in simple transverse tibial shaft fractures treated with reamed nailing. © 2012 Springer-Verlag Berlin Heidelberg.
PubMed | Institute for Biomechanics, Stryker Osteosynthesis and Traumacenter Murnau e.V.
Type: Journal Article | Journal: European journal of trauma and emergency surgery : official publication of the European Trauma Society | Year: 2016
Modern intramedullary implants provide the option to perform compression at the fracture gap in long bone fractures via a compression screw mechanism. The aim of this study was to assess if the application of interfragmentary compression in the intramedullary nailing of tibia fractures could increase the union rate and speed of fracture healing.Sixty-three patients who suffered from an AO-type 42-A3 or 42-B2 fracture that was treated by reamed intramedullary nailing between 2003 and 2008 were included in this retrospective study. Twenty-five patients were treated with dynamic interlocking without compression while 38 were treated with compression nailing. The compression load of the dynamic proximal screw was calculated by postoperative X-ray and radiographs taken fourweeks after operation. Healing was assessed by radiological evaluation until the completion of bony healing or the disappearance of clinical symptoms. Nonunion was defined as the absence of radiological union and the persistence of clinical symptoms after sixmonths.Postoperative compression was applied at a mean load of 1,852N, and 980N remained after fourweeks. In the compression group, 19 open and 19 closed fractures occurred. In the non-compression group, 25 patients were included (14 closed and 11 open cases). Active compression decreased healing time significantly. Nonunion occurred in one compression patient and three non-compression patients.The results show that additional compression of the fracture gap can improve healing outcome in simple transverse tibial shaft fractures treated with reamed nailing.
Singh N.B.,Institute for Biomechanics |
Konig N.,Institute for Biomechanics |
Arampatzis A.,Humboldt University of Berlin |
Taylor W.R.,Institute for Biomechanics
PLoS ONE | Year: 2013
Background: Evaluation of task related outcomes within geriatric and fall-prone populations is essential not only for identification of neuromuscular deficits, but also for effective implementation of fall prevention strategies. As most tasks and activities of daily living are performed at submaximal force levels, restoration of muscle strength often does not produce the expected benefit in functional capacity. However, it is known that muscular control plays a key role in the performance of functional tasks, but it remains unclear to what degree muscular control and the associated neuromuscular noise (NmN) is age-related, particularly in the lower-extremities. Objectives: The aim of this study was to determine the effects of age and fall-pathology on the magnitude as well as the frequency of NmN during lower extremity force production. Methods: Sixteen young healthy adults, as well as seventy elderly women (36 healthy, 34 elderly fallers), performed force production tests at moderate levels (15% of maximum voluntary isometric contractions). Results: Elderly fallers exhibited the highest magnitude of NmN, while the highest frequency components of NmN tended to occur in the healthy elderly. Young subjects exhibited significantly more power in the low frequency ranges than either of the elderly groups, and had the lowest levels of NmN. Conclusion: These data suggest increased degeneration of muscular control through greater NmN in elderly fallers compared to healthy elderly or young subjects. This could possibly be associated with muscle atrophy and lower levels of motor unit synchronisation. © 2013 Singh et al.
PubMed | Ludwig Maximilians University of Munich and Institute for Biomechanics
Type: Journal Article | Journal: European journal of trauma and emergency surgery : official publication of the European Trauma Society | Year: 2015
It is known that the application of growth factors can enhance fracture healing in defect fractures. The role of bone marrow aspirate (BMA) in combination with BMP-7 and the dosage of rh BMP-7 are still under discussion. Our hypothesis was that the combination of rh-BMP-7 with BMA can heal bone defects more effectively than rh-BMP-7 alone.Twenty-eight rats obtained a 5 mm critical size defect in the diaphysis of the right femur which was stabilized by a plate. Rh-BMP-7 was applied at 10 and 200 g either with collagen or together with collagen and BMA. Collagen only and collagen with BMA served as control groups. Blood flow was assessed by laser Doppler flowmetry in regular time intervals until euthanasia. Callus formation and bone density were measured by micro-computed tomography and biomechanical stability was evaluated by torsional testing at 4 weeks, postoperatively.Blood flow increased at the operated side after surgery until the second postoperative week independent of treatment. Animals treated with high dose BMP-7 showed significantly (p = 0.001) increased mechanical stiffness independent of BMA treatment. Failure loads were lowest for the two control groups (p = 0.001). The reduction of the BMP-7 dose led to less callus tissue and lower biomechanical stability. BMA did not show significant influence on bone healing.The combination of an rhBMP-7 dose that would be equivalent to a dose used clinically in humans with bone marrow aspirate does not heal a critical bone defect more effectively than the same rhBMP-7 dose alone.