Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells. Keywords: adipose tissue; alopecia; burn wounds; diabetic ulcers; micro-tissues; stem cell

In Vitro and In Vivo Effects of IGF-1 Delivery Strategies on Tendon Healing: A Review

Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors have been under view for decades. Insulin-like growth factor-1 (IGF-1) is one of the used growth factors and has been applied to tenocyte in vitro cultures as well as in animal preclinical models and to human patients due to its anabolic and matrix stimulating effects. In this narrative review, we cover the current literature on IGF-1, its mechanism of action, in vitro cell cultures (tenocytes and mesenchymal stem cells), as well as in vivo experiments. We conclude from this overview that IGF-1 is a potent stimulus for improving tendon healing due to its inherent support of cell proliferation, DNA and matrix synthesis, particularly collagen I, which is the main component of tendon tissue. Nevertheless, more in vivo studies have to be performed in order to pave the way for an IGF-1 application in orthopedic clinics. Keywords: tenocytes; stem cells; growth factor; collagen; PI3K/Akt/mTOR pathway; Ras-MAPK pathway; PLC pathwa

Retrograde Free Venous Flaps for Extremity Reconstruction: A Roadmap

Background and Objectives: Retrograde free venous flaps represent a separate entity among free venous flaps: their physiology is still unclear, but they provide an immediate visible refill after reconnection, with a similar behaviour to conventional flaps. Therefore, the dimensions and the indications of these flaps can be extended beyond what was previously believed, and they can be easily customized, including with respect to tendons and nerves. Nevertheless, they are still debated and regarded as unsafe. Materials and Methods: From 2012 to 2019, we performed 31 retrograde free venous flaps on 31 patients to reconstruct hands, digits, and in one case the heel. All the flaps were arterialized in a retrograde manner; the donor site was the forearm in 28 cases, the foot in 2 cases, and the calf in 1 case. We recorded the size, vein architecture, donor site, donor artery, donor morbidity, function for composite and non-composite flaps, immediate complications, late complications, survival rate, and the number of revisions. We recorded the hand function when appropriate. A total of 10 flaps were also intraoperatively studied with indocyanine green to monitor their hemodynamical behaviour. Results: All the patients were followed for an average of 8 months (6-15). The flap dimensions ranged from 6 cm$^{2}$ to 136 cm$^{2}$. All the flaps, except two that had complete necrosis, survived. Two flaps had partial necrosis. There was no correlation between necrosis and the size of the flap, with one case of necrosis and one of partial necrosis in the small flaps (<10 cm$^{2}$). None of the cases with partial necrosis needed a new flap. Two flaps developed a late arterio-venous shunt that was ligated. Conclusions: The retrograde free venous flaps proved to be a useful tool for complex reconstructions of the hand and extremities. They can provide a large island of pliable skin and composite tissue with tendons and nerves, but surgeons must be aware of some caveats

In-vivo Measurement of Wrist Movements During the Dart-Throwing Motion Using Inertial Measurement Units

Background: This study investigates the dart-throwing motion (DTM) by comparing an inertial measurement unit-based system previously validated for basic motion tasks with an optoelectronic motion capture system. The DTM is interesting as wrist movement during many activities of daily living occur in this movement plane, but the complex movement is difficult to assess clinically. Methods: Ten healthy subjects were recorded while performing the DTM with their right wrist using inertial sensors and skin markers. Maximum range of motion obtained by the different systems and the mean absolute difference were calculated. Results: In the flexion-extension plane, both systems calculated a range of motion of 100◦ with mean absolute differences of 8◦ , while in the radial-ulnar deviation plane, a mean absolute difference of 17◦ and range of motion values of 48◦ for the optoelectronic system and 59◦ for the inertial measurement units were found. Conclusions: This study shows the challenge of comparing results of different kinematic motion capture systems for complex movements while also highlighting inertial measurement units as promising for future clinical application in dynamic and coupled wrist movements. Possible sources of error and solutions are discusse

Delineation of the healthy rabbit kidney by immunohistochemistry - A technical note.

Pre-clinical animal models are needed to investigate and study kidney injuries and diseases. The rabbit kidney model is frequently used because various important parameters can be assessed with it. For example, histology and immunohistochemistry are indispensable as tissue morphology and composition can be investigated qualitatively as well as quantitatively. Here, different histological and immunohistochemical stainings were performed in the rabbit healthy naïve kidney tissue. First, overnight formalin fixation followed by paraffin embedding and cryopreservation with a subsequent 10-minute formalin fixation prior to staining were compared. Cryosections showed a more pronounced staining pattern, with clear borders at low magnifications, but blurred borders at higher magnifications. Then, antigen retrieval (AR) for paraffin embedded sections resulted in more prominent corresponding signals compared to stainings without AR. Moreover, several advantages and disadvantages of chromogenic versus immunofluorescence stainings were considered. Chromogenic staining was advantageous compared to immunofluorescence for collagen I and III, and to a minor degree for fibronectin. Finally, distinct structures, such as the pelvis, the calices, the glomeruli and tubuli, were stained in serial sections with diverse immunohistochemical stainings in order to delineate their composition. The following stainings were performed: standard Haematoxylin&Eosin and Elastica van Gieson staining, collagen I, collagen III, fibronectin, α-SMA, ki-67 and protease-activated receptor-2 (PAR-2). While chromogenic stainings of collagen I and collagen III were particularly useful to depict kidney structures in paraffin sections compared with cryosections, cryosections immunofluorescently stained for α-SMA were superior to paraffin sections, particularly at higher magnifications. With regard to specific structures, we found renal vessel walls positive for fibronectin and α-SMA, while the Bowman's capsule was only positive for fibronectin and α-SMA showed only tiny spots. The mesangial cells of the glomeruli and the distal tubuli were PAR-2 positive, while the proximal tubuli were PAR-2 negative

Cutaneous Invasive Fungal Infections with Saksenaea Species in Immunocompetent Patients in Europe: A Systematic Review and Case Report

Invasive fungal infections from Saksenaea, a fungus belonging to the Mucorales, have been rarely reported in central European climate zones. This study aims to raise awareness of invasive cutaneous infections with Saksenaea species. The first case of a cutaneous infection was diagnosed in Switzerland in an immunocompetent 79-year-old patient. A minor skin trauma of her left lower leg led to a fulminant infection causing necrosis and extensive loss of tissue. The combination of surgical debridement and administration of antifungal agents averted a prolonged course with a possible worse outcome. A pedicled hemisoleus muscle flap was used to reconstruct the defect and treatment was continued for 63 days. Methods: A systematic review in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis guidelines was conducted to identify all European cases of infection with Saksenaea species in immunocompetent hosts. The epidemiology, clinical presentation, microbiological diagnosis, and management of cases reported in Europe were summarized and analyzed. Conclusions: The prognosis of soft tissue infections with Saksenaea species. depends on early diagnosis and appropriate antifungal and surgical treatment. Reconstruction can be successful under ongoing antifungal treatment

Comparison of a New Inertial Sensor Based System with an Optoelectronic Motion Capture System for Motion Analysis of Healthy Human Wrist Joints

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p-values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings

Comparison of a New Inertial Sensor Based System with an Optoelectronic Motion Capture System for Motion Analysis of Healthy Human Wrist Joints

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p-values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings

Delineation of the healthy rabbit heart by immunohistochemistry - A technical note

Heart failure poses a big health problem and may result from obesity, smoking, alcohol and/or growing age. Studying pathological heart tissue demands accurate histological and immunohistochemical stainings in animal models, including chromogenic and fluorescent approaches. Moreover, a reliable set of healthy heart stainings and labeling are required, in order to provide a reference for the pathological situation. Heart and brain tissue of a healthy rabbit were collected, and different histological key steps were compared, such as paraffin embedding after formalin fixation versus cryopreservation; an antigen retrieval (AR) step in processing paraffin sections versus the same procedure without AR; or a chromogenic with a fluorescent detection system, respectively. Using serial sections, we stained the same morphological structure with classic approaches (HE, Masson Goldner Trichrome (GT) and Elastica van Gieson (EL)) and with different markers, including collagen I, collagen III, fibronectin, α-SMA, protease-activated receptor-2 (PAR-2) which is an inflammation-related marker, and ki67 for proliferating cells. Differences between conditions were quantitatively assessed by measuring the color intensity. Generally, cryosections exhibited a more prominent signal intensity in immunohistochemically labeled sections than in paraffin sections, but the strong staining was slurry, which sometimes impeded proper identification of morphological structures, particularly at higher magnifications. In addition, the advantage of an AR step was observed when compared to the condition without AR, where signal intensities were significantly lower. Different stainings of the heart arteries and the myocardium revealed a clear distribution of extracellular matrix components, with prominent collagen III in the artery wall, but an absence of collagen III in the myocardium. Moreover, paraffin-embedded sections provided more distinct structures compared to cryosections after collagen III, ki67, fibronectin, and α-SMA labeling. As for the Purkinje cells that were depicted in the heart and the cerebellum (Purkinje neurons), we found GT staining most suitable to depict them in the heart, while HE as well as EL staining was ideal to depict Purkinje neurons in the cerebellum. In sum, we provide useful reference images with different stainings for researchers using the rabbit heart or brain model. Such images can help to decide which of the immunohistochemical protocols are valuable to reach a specific aim. Recommendations are given for the best visualization of the target structures and specific (immunohistochemical) staining