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Traumatische Nervenverletzungen gehen mit einer hohen Morbiditat und langen Rehabilitationszeiten einher. Das Ausmas der Nervenschadigung mit dem damit verbundenen Regenerationspotenzial kann oft erst im Verlauf eingeschatzt werden, wobei das Zeitfenster fur erfolgreiche chirurgische Interventionen begrenzt ist. Inzidenz und Verteilung traumatischer Nervenlasionen, Darstellung von Algorithmen zur Therapieentscheidung. Auswertung von Statistiken aus dem TraumaRegister DGU® sowie internationalen Registern. Diskussion von Grundlagenarbeiten und Expertenempfehlungen zu Diagnostik und Therapie. Ein strategisches Vorgehen bei der konservativen und operativen Behandlung von Nervenlasionen in Abhangigkeit vom Ausmas der Schadigung und dem resultierenden Regenerationspotenzial ist empfohlen. In Zusammenschau mit dem klinischen Verlauf konnen elektrophysiologische und bildgebende Diagnostik wie die Nervensonographie helfen, zwischen Neurapraxie, Axonotmesis und Neurotmesis zu unterscheiden.

Polytraumatisierte Brandverletzte stellen ein seltenes Patientenkollektiv dar und erfordern aufgrund der besonderen Kombinationsverletzung ein eigenes Behandlungskonzept. Vor dem Hintergrund dieses speziellen Verletzungsmusters stellt sich die Frage nach einem interdisziplinaren Behandlungsalgorithmus, insbesondere wenn tiefgradige Verbrennungen uber der Frakturzone lokalisiert sind. Grundlagen des vorliegenden Beitrags sind eine PubMed-basierte Literaturrecherche und eigene Erfahrungen eines universitaren Traumazentrums fur Schwerbrandverletzte mit Darstellung der besonderen therapeutischen Anforderungen und Zielsetzungen anhand eines Fallbeispiels. Die Auswertung der Literaturrecherche und eigener Behandlungsergebnisse kommt zu dem Ergebnis, dass Amputationen und Infektionen bei rechtzeitiger und interdisziplinarer Einbindung des plastischen Chirurgen durch fruhe kombinierte Frakturstabilisierung, Nekrosektomie und sofortige Hauttransplantation in Haufigkeit und Ausmas reduziert werden konnen. Plastisch-rekonstruktive Eingriffe ermoglichen zudem eine funktionelle und asthetische Wiederherstellung mit optimierter Prothesenversorgung. Polytraumatisierte Schwerbrandverletzte erfordern einen interdisziplinaren Behandlungsansatz, wobei Langenerhalt, Funktionalitat und Asthetik der betroffenen Extremitaten unter Vermeidung von Knochen- und Weichteilinfektionen oberstes Behandlungsprimat sind.

Traumatic nerve injuries are associated with a high morbidity and long rehabilitation times. The extent of a nerve lesion and the related regeneration potential can often only be estimated during the course, whereby the time window for successful surgical interventions is limited.The incidence and distribution of traumatic nerve lesions are reported. Algorithms for treatment decisions are presented.Statistics from the German TraumaRegister DGU® as well as international registers were evaluated. The results of basic research and expert recommendations for diagnostics and treatment are discussed.A strategic approach to conservative and surgical treatment of traumatic nerve injuries depending on the extent of injury and resulting regeneration potential is recommended. In conjunction with the clinical course, electrophysiology and imaging diagnostics, e.g. nerve sonography, can help to differentiate between neurapraxia, axonotmesis and neurotmesis.HINTERGRUND: Traumatische Nervenverletzungen gehen mit einer hohen Morbidität und langen Rehabilitationszeiten einher. Das Ausmaß der Nervenschädigung mit dem damit verbundenen Regenerationspotenzial kann oft erst im Verlauf eingeschätzt werden, wobei das Zeitfenster für erfolgreiche chirurgische Interventionen begrenzt ist.Inzidenz und Verteilung traumatischer Nervenläsionen, Darstellung von Algorithmen zur Therapieentscheidung.Auswertung von Statistiken aus dem TraumaRegister DGU® sowie internationalen Registern. Diskussion von Grundlagenarbeiten und Expertenempfehlungen zu Diagnostik und Therapie.Ein strategisches Vorgehen bei der konservativen und operativen Behandlung von Nervenläsionen in Abhängigkeit vom Ausmaß der Schädigung und dem resultierenden Regenerationspotenzial ist empfohlen. In Zusammenschau mit dem klinischen Verlauf können elektrophysiologische und bildgebende Diagnostik wie die Nervensonographie helfen, zwischen Neurapraxie, Axonotmesis und Neurotmesis zu unterscheiden.

In the field of tissue engineering, spherical phosphorescent microprobes are well suited to quantify the oxygen content in close proximity to the cells during their growth phase. When using standard seed trays like glass dishes, probe excitation and signal acquisition can be realized by applying a fluorescence microscope. However, when using a bulky bioreactor a custom-built optics system with a laser as the excitation source had to be employed. Here we describe the basic principles of spherical optical oxygen microprobes for use in standard cell cultures and the system modifications with a laser, which were required in order to perform similar measurements from a distance in bioreactor cultures.

Different families of snakes possess specialized infrared sensory organs which have evolved for thermoregulation as well as prey and predator detection. The sensor, a specialized “pore” found in the keratinized epidermal layer, is activated by infrared thermal radiation and transmits signals via the neuronal system through the trigeminal nerve. Here we present findings from anatomical and physiological studies of the infrared sensor of pit viper, python and boa using histology, optical coherence tomography, laser microdissection and capillary electrophoresis to identify and characterize a lipoprotein and its important role during sensor activation. Furthermore, the mechanism for signal detection and enhancement as well as reduction of background noise was simulated using neural network analysis based on the findings from histology. A high density of free nerve endings and multiple neural (i.e. dendrite) connections in the sensor organ are crucial for signal detection and processing and work as a filter to overcome background noise.

Noise is considered an artefact, in the practical use it is overcome by cool down the system in general at 77 K. We consider three biological examples which overcome noise by filtering the ratio between the signals and noise by using a distribution system. Noise is considered here in statistical terms poison, where the incident photon or otherwise in a detector and the detector has not influence and cannot increase.

In the present study we tested magnetosomes isolated from the magnetic bacterium Magnetospirillum gryphiswaldense for their magnetic qualities when embedded in three different environmental surroundings: (1) medium (Phosphate buffer saline PBS), (2) gelatin gel matrix and as (3) powder. (3) is used as base line (standard control). We studied the magnetic hysteresis, thermal degradation in relation to theoretical results obtained with natural magnetosomes, by using an indirect analysis with biomimetic principles.

Metabolic pathways are enzyme-catalyzed reactions that can be described by the Michaelis-Menten equation. The inherent problem with Michaelis-Menten kinetics is that the model is not reversible. Reverse catalysis, which is common in metabolic pathways, can be better described by Cell Communication Protocol© which offers a Self-Organizing Map (SOM) for the visualization of the enzyme-catalyze reactions. Neural gas, an algorithm for finding optimal data, is added to the SOM and allows for an increase in the weight space to handle the potential complexity of enzyme-catalysis with the use of back propagation, the system allows for the modeling of reverse reactions.

Human mesenchymal stem cells derived from adipose tissue (AD-hMSCs) represent a promising source for tissue engineering and are already widely used in cell therapeutic clinical trials. Until today, an efficient and sustainable cell labeling system for cell tracking does not exist. We evaluated transient transfection through electroporation for cell labeling and compared it with lentiviral transduction for AD-hMSCs. In addition, we tested whether nonsense DNA or a reporter gene such as enhanced green fluorescent protein (EGFP) is the more suitable label for AD-hMSCs. Using electroporation, the transfection efficiency reached a maximal level of 44.6 ± 1.1% EGFP-positive cells after selective and expansive cultivation of the mixed MSC population, and was 44.5 ± 1.4% after gene transfer with Cyanin3-marked nonsense-label DNA, which remained stable during 2 weeks of nonselective cultivation (37.2 ± 4.7% positive AD-hMSCs). Electroporation with both nonsense DNA and pEGFP-N1 led to a slight growth retardation of 45.2% and 59.1%, respectively. EGFP-transfected or transduced AD-hMSCs showed a limited adipogenic and osteogenic differentiation capacity, whereas it was almost unaffected in cells electroporated with the nonsense-label DNA. The nonsense DNA was detectable through quantitative real-time polymerase chain reaction for at least 5 weeks/10 passages and in differentiated AD-hMSCs. EGFP-labeled cells were trackable for 24 h in vitro and served as testing cells with new materials for dental implants for 7 days. In contrast, lentivirally transduced AD-hMSCs showed an altered natural immune phenotype of the AD-hMSCs with lowered expression of two cell type defining surface markers (CD44 and CD73) and a relevantly decreased cell growth by 71.8% as assessed by the number of colony-forming units. We suggest electroporation with nonsense DNA as an efficient and long-lasting labeling method for AD-hMSCs with the comparably lowest negative impact on the phenotype or the differentiation capacity of the cells, which may, therefore, be suitable for tissue engineering. In contrast, EGFP transfection by electroporation is efficient but may be more suitable for cell tracking within cell therapies without MSC differentiation procedures. Since current protocols of lentiviral gene transduction include the risk of cell biological alterations, electroporation seems advantageous and sustainable enough for hMSC labeling.

We present a new method for noninvasive real-time oxygen measurement inside three-dimensional tissue-engineered cell constructs in static and dynamic culture settings in a laminar flow bioreactor. The OPAL system (optical oxygen measurement system) determines the oxygen-dependent phosphorescence lifetime of spherical microprobes and uses a two-frequency phase-modulation technique, which fades out the interference of background fluorescence from the cell carrier and culture medium. Higher cell densities in the centrum of the scaffolds correlated with lower values of oxygen concentration obtained with the OPAL system. When scaffolds were placed in the bioreactor, higher oxygen values were measured compared to statically cultured scaffolds in a Petri dish, which were significantly different at day 1–3 of culture. This technique allows the use of signal-weak microprobes in biological environments and monitors the culture process inside a bioreactor.

Ausgedehnte Schadeldefekte entstehen zum einen im Rahmen onkologischer Erkrankungen, posttraumatisch oder postinterventionell. Ein nach der Primar- oder Sekundarversorgung in der Neurochirurgie, Hals-Nasen-Ohren-Heilkunde bzw. Schadelbasischirurgie eintretender komplikationsbehafteter Verlauf mit Weichteilverlusten ergibt die Notwendigkeit eines interdisziplinaren plastisch-chirurgischen Komplikationsmanagements. In diesem Ubersichtsartikel werden beispielhaft die Moglichkeiten der plastischen Weichteilrekonstruktion anhand reprasentativer Fallbeispiele dargestellt.

The fire beetle, Melanophila acuminata (Coleoptera: Buprestidae), senses infrared radiation at wavelengths of 3 and 10–25 microns via specialized protein-containing sensilla. Although the protein denatures outside of a biological system, this detection mechanism has inspired our bottom-up approach to produce single zinc phosphide microwires via vapour transport for IR sensing. The Zn3P2 microwires were immobilized and electrical contact was made by dielectrophoresis. Photoconductivity measurements have been extended to the near IR range, spanning the Zn3P2 band gaps. Purity and integrity of the Zn3P2 microwires including infrared light scattering properties were confirmed by infrared transmission microscopy. This biomimetic microwire shows promise for infrared chip development.

Cellular proliferation and differentiation during angiogenesis and osteogenesis require the communication of different cell types through growth factors and their receptors. Vascular endothelial growth factor (VEGF-A) plays an important role in osteoblast and endothelial cell intercommunication. We have investigated the effect of monocultures and indirect coculture of foetal rat calvarial (FRC) osteoblasts and microvascular endothelial cells (ECs) on nodule formation, proliferation, and mRNA-expression of VEGF-A and its receptors during culturing. Despite increased nodule formation in the presence of dexamethasone (Dex) in monocultures, the number of nodules and alkaline phosphatise activity were decreased in cocultured FRCs. VEGF mRNA expression over the differentiation period showed the expression of most Vegf isoforms is biphasic in both FRCs and ECs, whereas receptor expression was quite variable; however, that of Np-2 in FRCs increased steadily and significantly from 8 h to 14 days after an initial drop in expression. Significant changes in the proportion of Vegfa by Day 14 were noted mainly in the matrix-bound variants Vegf144 and Vegf188 in ECs and osteoblasts, respectively. Less striking results were seen in the expression of the soluble isoforms in either cell type. These results have identified expression of Vegf144 in osteoblasts, suggesting a possible autocrine and/or paracrine role that is affecting osteoblast mineralisation along with Vegf188, as well as possible early roles of these isoforms in initial cell attachment. Further study of VEGF expression in coculture and Vegf144 will lead to better understanding of its role in cell-cell communication and bone development.

Purpose Patients with burns utilise intensive medical care and rehabilitation. Deep dermal burns lead to scar contractures. Virtually no published data exists on costs for treatment of acute burns in comparison to burn sequelae. Our purpose was to collect financial data on burn therapy to estimate the socio-economic burden of thermal injuries. Methods German-DRG for in-patient treatment of burns was collected from our burn center. DRG-related T95.- coding served as a search tool for burn associated sequelae. To include rehabilitation costs, data from the largest health care insurance and a workmen compensation fund were acquired. Findings Acute burn treatment comprised 92% of costs for intensive care with approximately 4.600 EUR per percent total burned surface area (TBSA). Expenses for non-intensive care patients were significantly lower than for burn sequelae. Rehabilitation expenses were 4.4-fold higher than costs for acute burns including 59% for manual therapy and 37% for auxiliary material. Conclusions TBSA multiplied by factor 4600 could serve for cost calculation of severely burned patients. Approximately 0.3 billion EUR in total or 270.000 EUR per patient/year were spent on burn sequelae. Early admission to specialized burn centers is advocated with state-of-the-art treatment to minimize burn sequelae and health care expenses.

We present a laminar flow reactor for bone tissue engineering that was developed based on a computational fluid dynamics model. The bioreactor design permits a laminar flow field through its specific internal shape. An integrated bypass system that prevents pressure build-up through bypass openings for pressure release allows for a constant pressure environment during the changing of permeability values that are caused by cellular growth within a porous scaffold. A macroporous ceramic scaffold, composed of zirconium dioxide, was used as a test biomaterial that studies adipose stem cell behavior within a controlled three-dimensional (3D) flow and pressure environment. The topographic structure of the material provided a basis for stem cell proliferation and differentiation toward the osteogenic lineage. Dynamic culture conditions in the bioreactor supported cell viability during long-term culture and induced cell cluster formation and extra-cellular matrix deposition within the porous scaffold, though no complete closure of the pores with new-formed tissue was observed. We postulate that our system is suitable for studying fluid shear stress effects on stem cell proliferation and differentiation toward bone formation in tissue-engineered 3D constructs.

Vollschichtige Hautdefekte uber funktionellen Strukturen (Sehnen, Gefase) oder denudiertem Knochen an den Extremitaten machen in der Regel aufwandige Weichteilplastiken zur Defektdeckung notwendig. Als neue Option bei der Defektdeckung steht die bovine Kollagen-Elastin-Matrix MATRIDERM® zur Verwendung als Neodermis unter Hauttransplantaten zur Verfugung. Kann die einzeitige Transplantation mit MATRIDERM® und ausgedunnter Vollhaut oder Spalthaut uber denudierten Knochen oder freiliegenden Sehnen eine suffiziente Defektdeckung erreichen? Bei insgesamt 10 Patienten wurde anstatt plastisch-chirurgischer Defektdeckungen, MATRIDERM® in Kombination mit Spalthaut/Vollhaut in einem einzeitigen Deckungsverfahren angewandt. Es wurde die Einheilungsrate der einzeitig und kombiniert verwandten Transplantate auf einem generell mit grosen Hauttransplantatverlusten verbundenem Wundgrund (denudierter Knochen und Sehnen ohne Paratenon) ermittelt. Bei 9 von 10 Patienten konnte mit dem kombinierten Verfahren durch MATRIDERM® und Hauttransplantation eine vollstandige Defektdeckung erzielt werden. Dabei war ein einzeitiger Wundverschluss uber freiliegenden Sehnen ohne Paratenon in 4 von 5 Lokalisationen unter Erhalt der Funktion zu erreichen gewesen. Uber deperiostierten knochernen Defekten war ein einzeitiger komplikationsfreier Verschluss jedoch nur in 2 von 6 Lokalisationen erfolgreich gewesen. Insgesamt konnte jedoch mit einer zweiten Spalthauttransplantation bei vaskularisiertem MATRIDERM® ein vollstandiger Wundverschluss an der Wunde mit freiliegender Sehne und in 3 der 4 knochernen Lokalisationen erzielt werden. Bei einem Patienten mit freiliegendem Olecranon konnte eine lokale Transpositionslappenplastik zum abschliesenden Verschluss angewendet werden. Durch die ein- bzw. zweizeitige Verwendung von MATRIDERM® uber frei liegenden Sehnen sowie Knochen kann ein effektiver Defektverschluss ohne die Notwendigkeit eines komplizierteren plastisch-rekonstruktiven Verfahrens erzielt werden. Einen Ersatz fur Lappenplastiken in Bezug auf ihre Funktionalitat kann dieses Verfahren nicht darstellen. Durch die Verwendung von MATRIDERM® besteht aber in ausgewahlten Fallen eine erweiterte Indikationsmoglichkeit fur Spalthauttransplantationen bei plastisch-rekonstruktiven Eingriffen.

In recent years, there has been a huge increase of injectable filler materials on the aesthetic market to correct wrinkles, aging lines, or volume deficits in the face. Despite their nontoxicity and low immunologic reactivity, they can induce a foreign body reaction and formation of inflammatory nodules or granulomas. We report a case of severe complications with granuloma formation and bacterial superinfection after lip and cheek augmentation with the new injectable filler DermaLive®.

A three-dimensional computational fluid dynamics- (CFD-) model based on a differential pressure laminar flow bioreactor prototype was developed to further examine performance under changing culture conditions. Cell growth inside scaffolds was simulated by decreasing intrinsic permeability values and led to pressure build-up in the upper culture chamber. Pressure release by an integrated bypass system allowed continuation of culture. The specific shape of the bioreactor culture vessel supported a homogenous flow profile and mass flux at the scaffold level at various scaffold permeabilities. Experimental data showed an increase in oxygen concentration measured inside a collagen scaffold seeded with human mesenchymal stem cells when cultured in the perfusion bioreactor after 24 h compared to static culture in a Petri dish (dynamic: 11% O2versus static: 3% O2). Computational fluid simulation can support design of bioreactor systems for tissue engineering application.

Engineered MSCs from Patient-Specific iPS Cells, by Irina Eberle, Mohsen Moslem, Reinhard Henschler, Tobias Cantz Fate of Intravenously Injected Mesenchymal Stem Cells and Significance for Clinical Application, by Beate Wagner, Reinhard Henschler The Implications of Stem Cell Applications for Diseases of the Respiratory System, by Mei Ling Lim, Philipp Jungebluth, Paolo Macchiarini Potential of Mesenchymal Stem Cell Applications in Plastic and Reconstructive Surgery, by Birgit Weyand, Peter M. Vogt General Principles for the Regeneration of Bone and Cartilage, by Michael Jagodzinski, C. Haasper Adult Mesenchymal Stem Cells Explored in the Dental Field, by K. M. Fawzy El-Sayed, C. Dorfer, F. Fandrich, F. Gieseler, M. H. Moustafa, H. Ungefroren Mesenchymal Stem Cell Therapy and Lung Diseases, by Khondoker M. Akram, Sohel Samad, Monica Spiteri, Nicholas R. Forsyth Mesenchymal Stem Cells as Cellular Immunotherapeutics in Allogeneic Hematopoietic Stem Cell Transplantation, by Claudia Papewalis, Daniela Topolar, Barbara Gotz, Stefan Schonberger, Dagmar Dilloo New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes, by Aline M. Betancourt Interactions Between Mesenchymal Stem Cells and Dendritic Cells, by Grazia Maria Spaggiari, Lorenzo Moretta MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential, by Naomi D'souza, Jorge Sans Burns, Giulia Grisendi, Olivia Candini, Elena Veronesi, Serena Piccinno, Edwin M. Horwitz, Paolo Paolucci, Pierfranco Conte, Massimo Dominici Sources of Mesenchymal Stem Cells: Current and Future Clinical Use, by Michela Pozzobon, Martina Piccoli, Paolo De Coppi Role of the EU Framework in Regulation of Stem Cell-Based Products, by Giovanni Migliaccio, Cristina Pintus

Cellular proliferation and differentiation during angiogenesis and osteogenesis require the communication of different cell types through growth factors and their receptors. Vascular endothelial growth factor (VEGF-A) plays an important role in osteoblast and endothelial cell intercommunication. We have investigated the effect of monocultures and indirect coculture of foetal rat calvarial (FRC) osteoblasts and microvascular endothelial cells (ECs) on nodule formation, proliferation, and mRNA-expression of VEGF-A and its receptors during culturing. Despite increased nodule formation in the presence of dexamethasone (Dex) in monocultures, the number of nodules and alkaline phosphatise activity were decreased in cocultured FRCs. VEGF mRNA expression over the differentiation period showed the expression of most Vegf isoforms is biphasic in both FRCs and ECs, whereas receptor expression was quite variable; however, that of Np-2 in FRCs increased steadily and significantly from 8 h to 14 days after an initial drop in expression. Significant changes in the proportion of Vegfa by Day 14 were noted mainly in the matrix-bound variants Vegf144 and Vegf188 in ECs and osteoblasts, respectively. Less striking results were seen in the expression of the soluble isoforms in either cell type. These results have identified expression of Vegf144 in osteoblasts, suggesting a possible autocrine and/or paracrine role that is affecting osteoblast mineralisation along with Vegf188, as well as possible early roles of these isoforms in initial cell attachment. Further study of VEGF expression in coculture and Vegf144 will lead to better understanding of its role in cell-cell communication and bone development.

Novel therapy with mesenchymal stem cells from bone marrow, adipose tissue, or other sources has raised high hopes for treatment of a variety of diseases. For plastic and reconstructive surgery, first pilot studies and clinical trials using stem cells for treatment of chronic wounds, radiation injury, or soft tissue augmentation have furnished encouraging results compared with the limitations of standard therapy, for example autologous fat grafting. Further research must be conducted to reveal the complex physiological interactions between activated stem cells and the host environment. Long-term effects and safety aspects of these novel treatment options also require randomized controlled studies. For future clinical applications, guidelines and standardized procedures for stem cell isolation and preparation, and techniques for application must be established.

The introduction of mesenchymal stem cells (MSC) into the field of tissue engineering for bone and cartilage repair is a promising development, since these cells can be expanded ex vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into different cell lineages. Mesenchymal stem cells isolated from various tissues have been intensively studied and characterized by many research groups. To obtain functionally active differentiated tissue, tissue engineered constructs are cultivated in vitro statically or dynamically in bioreactors under controlled conditions. These conditions include special cell culture media, addition of signalling molecules, various physical and chemical factors and the application of different mechanical stimuli. Oxygen concentration in the culture environment is also a significant factor which influences MSC proliferation, stemness and differentiation capacity. Knowledge of the different aspects which affect MSC differentiation in vivo and in vitro will help researchers to achieve directed cell fate without the addition of differentiation agents in concentrations above the physiological range.

The introduction of mesenchymal stem cells (MSC) into the field of tissue engineering for bone and cartilage repair is a promising development, since these cells can be expanded ex vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into different cell lineages. Mesenchymal stem cells isolated from various tissues have been intensively studied and characterized by many research groups. To obtain functionally active differentiated tissue, tissue engineered constructs are cultivated in vitro statically or dynamically in bioreactors under controlled conditions. These conditions include special cell culture media, addition of signalling molecules, various physical and chemical factors and the application of different mechanical stimuli. Oxygen concentration in the culture environment is also a significant factor which influences MSC proliferation, stemness and differentiation capacity. Knowledge of the different aspects which affect MSC differentiation in vivo and in vitro will help researchers to achieve directed cell fate without the addition of differentiation agents in concentrations above the physiological range.

Novel therapy with mesenchymal stem cells from bone marrow, adipose tissue, or other sources has raised high hopes for treatment of a variety of diseases. For plastic and reconstructive surgery, first pilot studies and clinical trials using stem cells for treatment of chronic wounds, radiation injury, or soft tissue augmentation have furnished encouraging results compared with the limitations of standard therapy, for example autologous fat grafting. Further research must be conducted to reveal the complex physiological interactions between activated stem cells and the host environment. Long-term effects and safety aspects of these novel treatment options also require randomized controlled studies. For future clinical applications, guidelines and standardized procedures for stem cell isolation and preparation, and techniques for application must be established.

The purpose of this study is to improve the design of a bioreactor for growing bone and other three-dimensional tissues using a computational fluid dynamics (CFD) software to simulate flow through a porous scaffold, and to recommend design changes based on the results. Basic requirements for CFD modeling were that the flow in the reactor should be laminar and any flow stagnation should be avoided in order to support cellular growth within the scaffold. We simulated three different designs with different permeability values of the scaffold and tissue. Model simulation addressed flow patterns in combination with pressure distribution within the bioreactor. Pressure build-up and turbulent flow within the reactor was solved by introduction of an integrated bypass system for pressure release. The use of CFD afforded direct feedback to optimize the bioreactor design.

One aspect of tissue engineering represents modelling of the extracellular matrix of connective tissue as the fiber network arrangement of the matrix determines its tensile strength. In order to define the correct position of the e.g. collagen in a structure, an optimized tertiary structure must be characterized. Existing approaches of protein models consider random packing of rigid spheres. We propose an alternative strategy to model protein structure by focusing on the folding. Our model considers (a) segments of amino-acid peptides or beads, (b) hydrogen bond distances, and (c) the distance geometry as functional components rather than minimizing distances between the centers of atoms. We reduced the molecular volume by using concepts from low dimensional topology, such as braids and surfaces, via differential geometry. A braid group maintains the continuity of a sequence while the spatial minimization is performed, and guarantees the continuity during the process. We have applied this approach to different examples of known protein sequences using ab initio protocols of ProteoRubix Systems™. Sequence files of three different proteins types were tested and modeled by ProteoRubix™ and compared to models derived by other methods. ProteoRubix™ created near-identical models with minimal computational load. This model can be expanded to large, multi-molecular network structures.

Mesenchymal stem cells and 3D biomaterials are a potent assembly in tissue engineering. Today, a sizable number of biomaterials has been characterized for special tissue engineering applications. However, diverse material properties, such as soft or hard biomaterials, have a specific influence on cell behavior. Not only the cell attachment and proliferation, but also differentiation is controlled by the microenvironment. Material characteristics such as pore size, stiffness, roughness, and geometry affect not only the cell attachment and proliferation, but also the differentiation behavior of mesenchymal stem cells. Optimization of these features might enable direct differentiation without adjustment of the culture medium by applying expensive growth or differentiation factors. Future aspects include the design of multilayered biomaterials, where each zone fulfills a distinct function. Moreover, the embedding of growth and differentiation factors into the matrix with a controlled release rate might be advantageous to direct differentiation.

Definition. Als Skalp wird die behaarte Kopfhaut bezeichnet, deren Hautdicke mit 3–8 mm die dickste des ganzen Korpers ist. Der Skalp setzt sich aus mehreren Schichten zusammen: Haut (Epidermis und Kutis), Subkutangewebe, Galea aponeurotica, lockeres Bindegewebe, und das darunter liegende Perikranium und angrenzendes Kranium, bestehend aus Tabula externa und Tabula interna, die wiederum nach innen mit den Hirnhauten (Dura mater, Arachnoidea mater, Pia mater) das Gehirn bedeckt (◘ Abb. 13.1).

Fur die Erkennung von latenten und manifesten Vorschaden sind eine genaue Anamneseerhebung, gezielte Befragung und die allgemeine klinische Untersuchung wichtig.

Collagen and ceramic matrices are extracellular scaffolds frequently used for bone tissue engineering. Human mesenchymal stem cells from adipose tissue with their unique properties for multipotent differentiation were cultured on a microporous collagen scaffold (Matriderm) and a macroporous ceramic scaffold (Sponceram) under static culture and in a dynamic flow environment in a laminar flow bioreactor. Both matrices differed in respect to cellular distribution after seeding which depended on pore size of the matrix. Cultivation under dynamic flow conditions influenced cellular morphology, collagen fiber alignment and extracellular matrix deposition compared to static culture. The flow rate had an effect on the amount of extracellular matrix formed by mesenchymal stem cells on the ceramic matrix. Further studies are necessary to reveal the ideal matrix and environmental culture conditions for bone tissue engineering.

Mesenchymal stem cells and 3D biomaterials are a potent assembly in tissue engineering. Today, a sizable number of biomaterials has been characterized for special tissue engineering applications. However, diverse material properties, such as soft or hard biomaterials, have a specific influence on cell behavior. Not only the cell attachment and proliferation, but also differentiation is controlled by the microenvironment. Material characteristics such as pore size, stiffness, roughness, and geometry affect not only the cell attachment and proliferation, but also the differentiation behavior of mesenchymal stem cells. Optimization of these features might enable direct differentiation without adjustment of the culture medium by applying expensive growth or differentiation factors. Future aspects include the design of multilayered biomaterials, where each zone fulfills a distinct function. Moreover, the embedding of growth and differentiation factors into the matrix with a controlled release rate might be advantageous to direct differentiation.

While bone marrow-derived mesenchymal stem cells are known and have been investigated for a long time, mesenchymal stem cells derived from the adipose tissue were identified as such by Zuk et al. in 2001. However, as subcutaneous fat tissue is a rich source which is much more easily accessible than bone marrow and thus can be reached by less invasive procedures, adipose-derived stem cells have moved into the research spotlight over the last 8 years.Isolation of stromal cell fractions involves centrifugation, digestion, and filtration, resulting in an adherent cell population containing mesenchymal stem cells; these can be subdivided by cell sorting and cultured under common conditions.They seem to have comparable properties to bone marrow-derived mesenchymal stem cells in their differentiation abilities as well as a favorable angiogenic and anti-inflammatory cytokine secretion profile and therefore have become widely used in tissue engineering and clinical regenerative medicine.

While bone marrow-derived mesenchymal stem cells are known and have been investigated for a long time, mesenchymal stem cells derived from the adipose tissue were identified as such by Zuk et al. in 2001. However, as subcutaneous fat tissue is a rich source which is much more easily accessible than bone marrow and thus can be reached by less invasive procedures, adipose-derived stem cells have moved into the research spotlight over the last 8 years.

The purpose of this study was to assess the feasibility of combined keratinocyte and dermal scaffold transplantation performed in a single step for treatment of full-thickness wounds. Cultured autologous keratinocytes were suspended in fibrin and grafted together with decellularised human dermis (Alloderm) in a porcine animal model, involving 10 animals over 4 weeks. Wound healing was evaluated by planimetry. Histology included morphological analysis as well as immunohistochemistry at regular intervals (1, 2 and 4 weeks). The results showed both successful histo-integration of the in vivo composite grafts and reduced wound contraction, compared with the control group (plain epithelial grafts). Histologically a neo-epithelium originated from the grafted cells on top of the decellularised dermis, as well as a reconstituted basement membrane. After 4 weeks cellular ingrowth into the dermal matrix could be observed. The successful combination of a keratinocyte-fibrin suspension and acellular dermis applied in a single step onto full-thickness wounds resulted in closure.

Bone is a complex tissue composed of a calcified extracellular matrix with specialized cells that produce, maintain, and resorb the bone. Bone also has a rich vascular and neural supply. Bone has a great capability of regeneration, healing, and remodelling that is influenced by external factors, such as stress forces, and internal regulators that include hormones, vitamins, and growth factors. These factors dictate bone biology, and variations result in pathophysiologic conditions that have clinical implications in hand surgery. Solutions to the challenges in hand surgery rely on a thorough understanding of the biology of bone.

In der Menschenrechtsarbeit von staatlichen wie nichtstaatlichen Organisationen zeigt sich seit einiger Zeit ein deutlicher Paradigmenwechsel. Statt die Einhaltung der Menschenrechte lediglich zu kontrollieren und im Falle ihrer Verletzung zu reagieren, setzt sich zunehmend die Sicht durch, dass ein umfassendes Praventionssystem zur Verhinderung von Menschenrechtsverletzungen von Noten ist. Ein wichtiges Mittel hierzu ist die Menschenrechtsbildung. Mit Hilfe der Vermittlung der Menschenrechte als volkerverbindende Werte- und Rechtsbasis soll die Wahrscheinlichkeit von Menschenrechtsverletzungen verringert werden. Die Hoffnung ist, dass eine „kritische Masse“ von Burgerinnen und Burgern um ihre Rechte weis, sie wertschatzen und fur sie eintreten soll, damit entwurdigende und menschenunwurdige Akte der Barbarei, wie sie sich unzahlig in Vergangenheit und Gegenwart finden, seltener oder sogar unmoglich werden.

A 40-day pot experiment was conducted to study the effect of N fertilizer application (0, 10 and 20 mg N kg−1 soil) on soil N turnover. Soil from a previous experiment was used, in which 4 different mineralization potentials (soil variants I–IV) had been established by stimulating microbial growth (simultaneous supply of C and N).