Stem cell fate is influenced by a number of factors and interactions that require robust control for safe and effective regeneration of functional tissue. Coordinated interactions with soluble factors, other cells, and extracellular matrices define a local biochemical and mechanical niche with complex and dynamic regulation that stem cells sense. Decellularized tissue matrices and synthetic polymer niches are being used in the clinic, and they are also beginning to clarify fundamental aspects of how stem cells contribute to homeostasis and repair, for example, at sites of fibrosis. Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.

/pdf/growth-factors-matrices-and-forces-combine-and-control-stem-4daxw4e632.pdf

Growth Factors, Matrices, and Forces Combine and Control Stem Cells

Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.

/pdf/nuclear-lamin-a-scales-with-tissue-stiffness-and-enhances-m0l552r7vs.pdf

Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation

The application of nanotechnology concepts to medicine joins two large cross-disciplinary fields with an unprecedented societal and economical potential arising from the natural combination of specific achievements in the respective fields. The common basis evolves from the molecular-scale properties relevant to the two fields. Local probes and molecular imaging techniques allow surface and interface properties to be characterized on a nanometer scale at predefined locations, while chemical approaches offer the opportunity to elaborate and address surfaces, for example, for targeted drug delivery, enhanced biocompatibility, and neuroprosthetic purposes. However, concerns arise in this cross-disciplinary area about toxicological aspects and ethical implications. This Review gives an overview of selected recent developments and applications of nanomedicine.

Nanomedicine--challenge and perspectives.

Osteoarthritis (OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.

/pdf/osteoarthritis-toward-a-comprehensive-understanding-of-2mospktvs7.pdf

Osteoarthritis: toward a comprehensive understanding of pathological mechanism.

Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

https://www.cell.com/biophysj/pdf/S0006-3495(12)03025-1.pdf

The nanomechanical signature of breast cancer

WISSENSCHAFTLICHER BEITRAG: 8. GOTS-Schweiz Tagung Universität Basel, 2. Februar 2006: Sportfähigkeit nach Verletzungen und Operationen

The comparison of electromyograms represents a challenge for data analysis. The aim of the project was to present a method that uses a minimal computational effort to resolve small but significant changes in the muscular activity that occur while walking with and without a knee brace. The wavelet transformed electromyograms were represented as intensity patterns that resolve the power of the signal in time and frequency. The intensity pattern of each electromyogram defines single points in a pattern space. The distance between these points in pattern space were used to detect and show the separation between the groups of electromyograms that were recorded while walking with and without a knee brace. The method proposes a distance versus angle representation to visually discriminate the intensity patterns. Once it has been shown that the differences are statistically significant, one can visualize the result in a difference intensity pattern that indicates at what time and at what frequency the electromyograms vary between the two conditions tested. It is to be expected that interventions that are more intrusive than a knee brace will reveal even more distinct differences

https://doc.rero.ch/record/299900/files/bmt.2004.009.pdf

Analyse der Veränderungen von Wavelet-transformierten elektromyographischen Signalen, wie sie beim Tragen einer Kniebandage entstehen = Analysis of wavelet transformed electromyographic signals that were altered by wearing a knee brace

The main purpose of this study is to evaluate the performance of different optical fibers after coupling an Er:YAG laser through them. This allows us to evaluate the feasibility of using them in future for minimally invasive ablation of bone, where a fiber has to be guided inside an endoscopic device. We coupled a high-power Er:YAG laser (λ = 2.94 μm) in different fibers separately. We analyzed the features and benefits of each fiber during the coupling process. The laser was operated at repetition rates of 1, 5, and 10 Hz in the energy range of 10-830 mJ. We used hollow-core, fluoride, sapphire and germanium oxide fibers with core sizes of 500, 450, 425 and 450 μm, respectively. The coupling efficiencies were determined by comparing the measured input and output energies for all the fibers. The resistance of each fiber to the input energy was evaluated by monitoring the stability of the measured output energy over time. From our observations, the coupling efficiencies for all the fibers were in the range 70 to 81 %. Due to the high coupling efficiency, all fibers have the potential to be used in endoscopic applications. However, their use will mostly depend on the individual need of a specific application.

Measurements of coupling efficiency of high power Er:YAG laser in different types of optical fibers

Biomechanics, treatment, and rehabilitation of cruciate ligament injuries

Operationsziel Wiederherstellung der anatomischen Achse der distalen Fibula zur Vermeidung oder Verlangsamung einer Arthrosebildung im oberen Sprunggelenk. Indikationen
 Posttraumatische Verkurzung der distalen Fibula, die meist kombiniert mit einer Ausenrotations- und Abduktionsfehlstellung des Ausenknochels auftritt. Fehlende, leichte oder nur masig fortgeschrittene Arthrose im oberen Sprunggelenk. Kontraindikationen
 Stark fortgeschrittene Arthrose im oberen Sprunggelenk. Gleichzeitiges Vorliegen eines Status nach lateraler Pilonimpressionsfraktur mit nicht wiederhergestellter Gelenkflache. Prekare Weichteilsituation nach Infektion oder Algodystrophie. Operationstechnik
 Lateraler Zugang zum Ausenknochel unter Beachtung alter Narben. Fibulaosteotomie (quer, schrag oder Z-formig). Befreiung der distalen Fibula und der Incisura fibularis tibiae von Narben, Osteophyten und Knochenfragmenten bis zur Fibulaspitze. Ein eventueller “Konflikt” im Bereich des medialen Knochels wird durch eine mediale Inzision angegangen (Narbenbefreiung, freie Knochenfragmente, Osteotomie Innenknochel). Anschliesend Korrektur von Lange, Rotation und Abduktion des Ausenknochels und Fixierung der Fragmente mit (AO-)Rekonstruktions- oder (AO-)LC-DC-Platte. Temporare Fixierung der Fibula in der Incisura fibularis tibiae mit zwei Kirschner-Drahten. Ergebnisse
 Alle acht operierten Patienten, drei Frauen und funf Manner in einem Durchschnittsalter von 43,5 (24–64) Jahren, wurden nach 3,9 (1,5–8,3) Jahren nachuntersucht. Sie waren ausnahmslos mit dem Resultat der Operation zufrieden und wurden den Eingriff erneut durchfuhren lassen. Radiologisch zeigte sich bei funf von sechs Patienten eine nur langsam fortschreitende Zunahme bereits praoperativ vorhandener arthrotischer Veranderungen. Bei zwei Patienten ohne praoperative radiologische Veranderungen fanden sich auch bei der letzten Nachkontrolle keine Arthrosezeichen. Die Art der Osteotomie (quer, schrag oder Z-formig) scheint auf das Endergebnis keinen Einfluss zu haben. Unsere Resultate bestatigen diejenigen alterer Studien. Die guten Ergebnisse waren unabhangig von der Lange des Intervalls zwischen Erstbehandlung und Korrekturosteotomie, der Art der Erstbehandlung und dem Alter der Patienten. In jedem Fall verlangsamte die Fibualosteotomie eine bis zum Zeitpunkt der Korrektur progressive Arthrose. Der Erfolg einer Verlangerungsosteotomie scheint einzig vom Ausmas der vor dem Korrektureingriff vorhandenen degenerativen Veranderungen im oberen Sprunggelenk abzuhangen.

Korrekturosteotomie der distalen Fibula bei posttraumatischer Fehlstellung

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