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Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.
As IoT systems have increased the number of deployed embedded devices drastically and most of these devices are used in safety or security critical environments, the education of embedded software engineers is more important than ever. A critical part of their education is the development of their intuition for secure and safe software. In this paper 1 1 This research was funded by the city of Vienna (MA-23 call 21, project no. 9). we present an evaluation system used to generate fast and accurate feedback for student submission in, but not limited to, embedded software development courses. The system can be used as a first feedback loop to outline to the students where problems exist in their code and give them the opportunity to analyze and correct their errors. These extra steps ensure that the students can and will be notified early about their mistakes and can search for correct solutions, supporting the student's learning process. We present the implementation of the system and analyze its deployment in a microcontroller software development lecture. This analysis was done by means of surveys of the students and lecturers as well as a statistical analysis of the student submissions. The results show that the students made use of this extra features and even would prefer to have this feedback in other software development lectures as well.