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Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process. Manual production steps require experienced personnel, are challenging to standardize and to scale up. Automated manufacturing has the potential to overcome these challenges, toward an increasing cost-effectiveness. One major obstacle for automation is the control and risk prevention of cross contaminations, especially when handling parallel production lines of different patient material. These critical steps necessitate validated effective and efficient cleaning procedures in an automated system. In this perspective, possible technologies, concepts and solutions to existing ATMP manufacturing hurdles are discussed on the example of a late clinical phase II trial TEP. In compliance to Good Manufacturing Practice (GMP) guidelines, we propose a dual arm robot based isolator approach. Our novel concept enables complete process automation for adherent cell culture, and the translation of all manual process steps with standard laboratory equipment. Moreover, we discuss novel solutions for automated cleaning, without the need for human intervention. Consequently, our automation concept offers the unique chance to scale up production while becoming more cost-effective, which will ultimately increase TEP availability to a broader number of patients.

Efficient heat transfer is essential for the economically sustainable operation of heat exchangers. Therefore, the internal flow is influenced systematically in various ways, for example by introducing macrostructures on the pipe surface. Since these measures may negatively affect the cleanability of the heat exchanger, it is necessary to investigate not only the increase in heat transfer, but also their impact on cleaning processes. For this purpose, the cleaning of sour milk in dimple-structured pipes is investigated experimentally. Both macroscopic and microbial cleaning tests are conducted to assess the influence of the surface’s macrostructure on cleanability. Two geometry variations of dimple-structured pipes are investigated and compared to a straight pipe Although fouling is enhanced by the dimple structures, a higher macroscopic cleaning rate can be achieved with the optimized dimple. Moreover, the residual microbial contamination decreases significantly due to the introduction of dimples. All in all, the cleaning experiments confirm the positive influence of the dimple structures on cleanability.

Microscopic and physico-chemical methods were used for a comprehensive surface characterization of different mechanically modified stainless steel surfaces. The surfaces were analyzed using high-resolution confocal microscopy, resulting in detailed information about the topographic properties. In addition, static water contact angle measurements were carried out to characterize the surface heterogeneity of the samples. The effect of morphological anisotropy on water contact angle anisotropy was investigated. The correlation between topography and wetting was studied by means of a model of wetting proposed in the present work, that allows quantifying the air volume of the interface water drop-stainless steel surface.

YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors. The molecular mechanisms driving proliferation in the pediatric brain cancer epdendymoma are poorly understood. Here the authors show that a YAP1- MAMLD1 fusion drives tumor formation in mice and show that the fusion protein can collaborate with the TEAD and NFI transcription factors.