Tissue engineering plays an important role in the production of skin equivalents for the therapy of chronic and especially burn wounds. Actually, there exists no (cellularized) skin equivalent which ...might be able to satisfactorily mimic native skin. Here, we utilized a laser-assisted bioprinting (LaBP) technique to create a fully cellularized skin substitute. The unique feature of LaBP is the possibility to position different cell types in an exact three-dimensional (3D) spatial pattern. For the creation of the skin substitutes, we positioned fibroblasts and keratinocytes on top of a stabilizing matrix (Matriderm®). These skin constructs were subsequently tested in vivo, employing the dorsal skin fold chamber in nude mice. The transplants were placed into full-thickness skin wounds and were fully connected to the surrounding tissue when explanted after 11 days. The printed keratinocytes formed a multi-layered epidermis with beginning differentiation and stratum corneum. Proliferation of the keratinocytes was mainly detected in the suprabasal layers. In vitro controls, which were cultivated at the air-liquid-interface, also exhibited proliferative cells, but they were rather located in the whole epidermis. E-cadherin as a hint for adherens junctions and therefore tissue formation could be found in the epidermis in vivo as well as in vitro. In both conditions, the printed fibroblasts partly stayed on top of the underlying Matriderm® where they produced collagen, while part of them migrated into the Matriderm®. In the mice, some blood vessels could be found to grow from the wound bed and the wound edges in direction of the printed cells. In conclusion, we could show the successful 3D printing of a cell construct via LaBP and the subsequent tissue formation in vivo. These findings represent the prerequisite for the creation of a complex tissue like skin, consisting of different cell types in an intricate 3D pattern.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture ...or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Publication bias is a major problem in evidence based medicine. As well as positive outcome studies being preferentially published or followed by full text publication authors are also more ...likely to publish positive results in English-language journals. This unequal distribution of trials leads to a selection bias in evidence l level studies, like systematic reviews, meta-analysis or health technology assessments followed by a systematic failure of interpretation and in clinical decisions. Publication bias in a systematic review occurs mostly during the selection process and a transparent selection process is necessary to avoid such bias. For systematic reviews/meta-analysis the PRISMA-statement (formerly known as QUOROM) is recommended, as it gives the reader for a better understanding of the selection process. In the future the use of trial registration for minimizing publication bias, mechanisms to allow easier access to the scientific literature and improvement in the peer review process are recommended to overcome publication bias. The use of checklists like PRISMA is likely to improve the reporting quality of a systematic review and provides substantial transparency in the selection process of papers in a systematic review.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Retroviruses are the original source of oncogenes. The discovery and characterization of these genes was made possible by the introduction of quantitative cell biological and molecular techniques for ...the study of tumour viruses. Key features of all retroviral oncogenes were first identified in src, the oncogene of Rous sarcoma virus. These include non-involvement in viral replication, coding for a single protein and cellular origin. The MYC, RAS and ERBB oncogenes quickly followed SRC, and these together with PI3K are now recognized as crucial driving forces in human cancer.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The increased availability of mapped environmental data calls for better tools to analyze the spatial characteristics and information contained in those maps. Publicly available, user-friendly and ...universal tools are needed to foster the interdisciplinary development and application of methodologies for the extraction of image object information properties contained in digital raster maps. That is the overarching goal of GuidosToolbox, which is a set of customized, thematically grouped raster image analysis methodologies provided in a graphical user interface and for all popular operating systems. The Toolbox contains a wide selection of dedicated algorithms and tools, which are complemented by batch-processing and pre- and post-processing routines, all designed to objectively describe and quantify various spatial properties of image objects in digital raster data. While first developed for the analysis of remote sensing data in environmental applications, the Toolbox now provides a generic framework that is applicable to image analysis at any scale and for any kind of digital raster data.
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is up-regulated in cancer. PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, is mutated in almost equal to30% of tumors of ...the prostate, breast, cervix, and endometrium. The most prominent of these mutants, represented by single amino acid substitutions in the helical or kinase domain, show a gain of enzymatic function, activate AKT signaling, and induce oncogenic transformation. We have carried out a genetic and biochemical analysis of these hot-spot mutations in PIK3CA. The results of this study suggest that the helical and kinase domain mutations trigger gain of function through different mechanisms. They show different requirements for interaction with the PI3K regulatory subunit p85 and with RAS-GTP. The gain of function induced by helical domain mutations is independent of binding to p85 but requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding but is highly dependent on the interaction with p85. We speculate that the contrasting roles of p85 and RAS-GTP in helical and kinase domain mutations reflect two distinct states of mutated p110α. These two states differ in mutation-induced surface charges and also may differ in conformational properties that are controlled by interactions with p85 and RAS-GTP. The two states do not appear mutually exclusive because the helical and kinase domain mutations act synergistically when present in the same p110α molecule. This synergism also supports the conclusion that the helical and kinase domain mutations operate by two different and independent mechanisms.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background
Magnesium-based bioabsorbable osteosynthesis material continues to receive increasing attention. The following study documents our experience with bioabsorbable magnesium screws in ...scaphoid fracture treatment in hopes to capture further evidence and successful application.
Methods
Eight acute scaphoid fractures and four nonunions were treated with the magnesium-based bioabsorbable compression screw MAGNEZIX
®
. Objective outcome was assessed by X-ray imaging and/or CT scan for bone healing. Clinical assessment was achieved using the modified Mayo Wrist Score. Patient-reported outcome measure was performed threefold via QuickDASH, PRWE, and EQ-5D-5L questionnaires in all patients. Follow-up was 32.5 months (SD 18.7) in the acute fracture group and 31 months (SD 7.4) in the nonunion group.
Results
Bone healing was achieved in all eight patients with acute scaphoid fractures and in three of four patients with scaphoid nonunion. The modified Mayo Wrist Score was 95 (SD 7.1) in fractures and 80 (SD 7.1) in nonunion patients during follow-up. QuickDASH score was 3.9 (SD 5.8) in fracture and 19.3 (SD 10.6) in nonunion patients. All but one patient (87,5%) with scaphoid fractures presented with a full health state during follow-up (EQ-5D-5L). Nonunion patients had problems in 10 out of 19 dimensions in EQ-5D-5L. Acute fractures presented with a score of 3.9 (SD 7.9) and nonunions with a score of 19.7 (SD 32.4) in PRWE total scoring during follow-up.
Conclusions
Magnesium-based implants have excellent clinical outcomes when used for scaphoid fractures in eight presented cases and good to moderate clinical outcomes when used for nonunions in three of four presented cases. Additional studies are required to further analyze the differentiated applicability in scaphoid nonunion as well as overall performance when compared to non-absorbable screws in larger cohorts.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve ...injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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