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Murnau am Staffelsee, Germany

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.

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.

News Article
Site: www.biosciencetechnology.com

Researchers in the field of mechanobiology are evolving our understanding of health by revealing new insights into how the body's physical forces and mechanics impact development, physiological health, and prevention and treatment of disease. At the Wyss Institute for Biologically Inspired Engineering at Harvard University, engineers and biomedical scientists have assembled to form collaborative teams that are helping to drive this exciting area of research forward toward real-world applications. Now, a new study suggests mechanically-driven therapies that promote skeletal muscle regeneration through direct physical stimulation could one day replace or enhance drug and cell-based regenerative treatments. Discovered by a team at the Wyss Institute and the Harvard School of Engineering and Applied Sciences, the finding was published on January 25 in the journal Proceedings of the National Academy of Sciences. "Chemistry tends to dominate the way we think about medicine, but it has become clear that physical and mechanical factors play very critical roles in regulating biology," said Harvard bioengineer David Mooney, Ph.D., senior author on the new study, who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "The results of our new study demonstrate how direct physical and mechanical intervention can impact biological processes and can potentially be exploited to improve clinical outcomes. " The multi-disciplinary team spanning the Wyss Institute's Programmable Nanomaterials and Bioinspired Robotics platforms was led by Mooney and also included soft roboticist Conor Walsh, Ph.D., who is a Wyss Core Faculty member, Associate Professor of Mechanical and Biomedical Engineering at Harvard SEAS and Founder of the Harvard Biodesign Lab, and biomechanical engineer Georg Duda, Ph.D., who is a Wyss Associate Core Faculty member, Vice-Director of the Berlin-Brandenburg Center for Regenerative Therapies (BCRT) and the Director of the Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration at Charité-Universitätsmedizin Berlin. In humans, up to half of body mass is made up of skeletal muscle, which plays a key role in locomotion, posture, and breathing. Although skeletal muscles can overcome minor tears and bruising without intervention, major injuries commonly caused by motor vehicle accidents, other traumas, or nerve damage can lead to extensive scarring, fibrous tissue, and loss of muscle function. The team applied combined murine models of muscle injury and hind limb ischemia to investigate two potential mechanotherapies: an implanted magnetic biocompatible gel and an external, soft robotic pressurized cuff. To alleviate severe muscle injuries, the team implanted a magnetized gel called a "biphasic ferrogel" so that it would be in direct contact with the damaged tissue. Another experimental group of mice did not receive the ferrogel implant, but instead were fitted with a soft robotic, non-invasive pressurized cuff over the injured leg. Then, the ferrogel was subjected to magnetic pulses to apply cyclic stimulation to the muscle, while pulses of air allowed the cuff to cyclically massage the hind leg. Both groups received two weeks of localized mechanical perturbation using the two distinct methods. The researchers discovered that cyclic mechanical stimulation provided by either magnetized gel or robotic cuff both resulted in a two-and-a-half-fold improvement in muscle regeneration and reduced tissue scarring over the course of two weeks, ultimately leading to an improvement in regained muscle function and an exciting new finding that mechanical stimulation of muscle alone can foster regeneration. To their surprise, the ferrogel implant and pressurized cuff also resulted in very similar levels of regeneration, suggesting that the use of non-invasive pressurized cuffs or devices could one day help heal patients suffering from severe muscle injuries. "Until now most approaches to muscle regeneration have been biologic, relying on the use of drugs or cells," said Christine Cezar, Ph.D., lead author on the study who completed her doctoral research at the Wyss Institute and Harvard SEAS. "Our finding that mechanical stimulation alone is enough to enhance muscle repair could open the door to new non-biologic therapies, or even combinatorial therapies that employ both mechanical and biological interventions to treat severely damaged skeletal muscles." The direct stimulation of muscle tissue increases the transport of oxygen, nutrients, fluids and waste removal from the site of the injury, which are all vital components of muscle health and repair. And according to Mooney, one of the most exciting aspects of this research is that its translation to the clinic in the form of a stimulatory device could be relatively rapid as compared to drug or cell therapies. Down the road, the principle of using mechanical stimulation to enhance regeneration or reduce formation of scarring or fibrosis could also be applied to a wide range of medical devices that interface mechanical components with body tissues. Currently, clinical devices are often plagued by the formation of thickened tissue capsules that form at the intersection of machine and man. The team plans to explore how the findings can make the jump from the laboratory to the clinic. "This work clearly demonstrates that mechanical forces are as important biological regulators as chemicals and genes, and it shows the immense potential of developing mechanotherapies to treat injury and disease," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is a pioneer and leader in the field of mechanobiology. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard SEAS. "The challenge now is to advance this new mechanotherapeutic approach from the bench to bedside, where the real impact on human lives can occur."

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.

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.

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