Placenta-specific trophoblast and tumor cells exhibit many common characteristics. Trophoblast cells invade maternal tissues while being tolerated by the maternal immune system. Similarly, tumor cells can invade surrounding tissues and escape the immune system. Importantly, both trophoblast and tumor cells are supported by an abetting microenvironment, which influences invasion, angiogenesis, and immune tolerance/evasion, among others. However, in contrast to tumor cells, the metabolic, proliferative, migrative, and invasive states of trophoblast cells are under tight regulatory control. In this review, we provide an overview of similarities and dissimilarities in regulatory processes that drive trophoblast and tumor cell fate, particularly focusing on the role of the abetting microenvironments.

Obesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a) into a pegylated lipid nanoparticle (PEG-LNP) formulation by a single-step microfluidic-assisted synthesis step. For the miRNA-loaded LNPs, the following system properties were determined: particle size, zeta potential, miRNA complexation efficiency, and cytotoxicity. We have used a human preadipocyte cell line to address the transfection efficiency and biological effects of the miRNA candidates at the gene and protein level. Our findings revealed that the upregulation of miR27a in preadipocytes inhibits adipogenesis by the downregulation of PPARγ and the reduction of lipid droplet formation. In contrast, miR26a transfection in adipocytes induced white adipocyte browning detected as the upregulation of uncoupling protein 1 (UCP1) as a marker of non-shivering thermogenesis. We conclude that the selective delivery of miRNAs by PEG-LNPs to adipocytes could offer new perspectives for the treatment of obesity and related metabolic diseases.

Neurostimulation employing photoactive organic semiconductors offers an appealing alternative to conventional techniques, enabling targeted action and wireless control through light. In this study, organic electrolytic photocapacitors (OEPC) are employed to investigate the effects of light‐controlled electric stimulation on neuronal networks in vitro and in vivo. The interactions between the devices and biological systems are characterized. Stimulation of primary rat cortical neurons results in an elevated expression of c‐Fos within a mature neuronal network. OEPC implantation for three weeks and subsequent stimulation of the somatosensory cortex leads to an increase of c‐Fos in neurons at the stimulation site and in connected brain regions (entorhinal cortex, hippocampus), both in the ipsi‐ and contralateral hemispheres. Reactivity of glial and immune cells after semi‐chronic implantation of OEPC in the rat brain is comparable to that of surgical controls, indicating minimal foreign body response. Device functionality is further substantiated through retained charging dynamics following explantation. OEPC‐based, light‐controlled electric stimulation has a significant impact on neural responsiveness. The absence of detrimental effects on both the brain and device encourages further use of OEPC as cortical implants. These findings highlight its potential as a novel mode of neurostimulation and instigate further exploration into applications in fundamental neuroscience.

Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship between scaffold mechanical properties and reactions at the biological interface remains poorly understood. This study examines the attachment and integration of soft hydrogels on the CAM using an accessible ex ovo system. Composite hydrogels of polyvinyl alcohol and Phytagel were fabricated by sterile freeze-thawing. CAM assays, as an alternative to traditional in vivo models, enabled the evaluation of the compatibility, attachment, and biointegration of hydrogels with three distinct compositions. The mechanomimetic properties of the hydrogels were assessed through cyclic compression-tension tests, with nominal peak stresses ranging from 0 . 26 to 2 . 82 kPa in tension and - 0 . 33 to - 2 . 92 kPa in compression. Mechanical attachment to the CAM was measured by pull-off tests after five days of incubation. On the first day, the interface strength was similar for all hydrogel compositions. On day 5 , softer hydrogels showed the greatest increase ( p = 0 . 008 ), followed by intermediate hydrogels ( p = 0 . 020 ), while the denser hydrogels showed negligible changes ( p = 0 . 073 ). Histological analyses revealed cell infiltration in 100 % of soft, 75 % of intermediate, and 13 % of dense hydrogels, suggesting that softer hydrogels integrate better into the CAM by facilitating cell migration and enhancing interface strength. Chicken embryo survival rates and cytotoxicity assays confirmed the biocompatibility of the hydrogels and supported their potential for use in soft, hydrated three-dimensional scaffolds that mimic tissue environments in dynamic biological systems. Statement of significance Current research on soft scaffold materials for cell cultures often overlooks the critical relationship between mechanical properties and biological integration of these materials with host tissues. Although hydrogels, as soft porous materials, hold promise for creating physiologically relevant environments, the mechanisms driving their attachment and biointegration, especially on the chorioallantoic membrane (CAM), remain largely unexplored. This study addresses this gap by investigating the interaction between soft hydrogels and the CAM, providing valuable insights into how material properties and microstructure influence cellular responses. Our findings emphasize the importance of understanding these dynamics to develop biocompatible scaffolds that better mimic tissue environments, advancing applications in three-dimensional cell cultures on CAM assays and other biological systems.

Soft biomaterials strongly influence cellular behavior by transmitting mechanical cues via well‐characterized mechanotransduction pathways. However, translating insights from simplified in vitro systems to complex in vivo responses remains a challenge. This review provides a framework for assessing the translational relevance of mechanobiological studies across different scales—from single cells and organoids to tissues and organs. First, we categorize soft biomaterials based on their architecture and mechanical features to establish consistent terminology. We then investigate how cells interpret the transmitted mechanical signals in advanced in vitro systems that simulate physiologically relevant mechanical environments. To discuss the translational potential, we present a scoring system and a comparative analysis demonstrating that physiological specificity, rather than experimental complexity, determines predictive value. Simple systems can yield highly translatable outcomes when mechanical cues mimic native conditions, while advanced models require careful validation to ensure their relevance. By integrating biomechanics, electrophysiology, and systems biology, we outline principles and validation strategies that enhance the predictive utility of mechanobiological findings and ultimately support the design of more effective biomaterials and tissue‐engineered systems.

Summary: Manufacturing red blood cells (RBCs) from human induced pluripotent stem cells (iPSCs) can improve our understanding of embryonic erythropoiesis, foster innovative treatments for RBC-related diseases, and ultimately address clinical blood supply shortages. However, existing systems face low efficiency, enucleation failure, and uncertainty about the develop-mental wave of cultured RBCs. We successfully used self-organized hemanoids to improve iPSC-derived RBC generation. Based on the hypothesis that cellular interactions and 3D organization promote hematopoietic cell fate, we aimed to thoroughly characterize hemanoids. We visualized the spatiotemporal emergence of hematopoiesis by generating a CD43-GFP reporter iPSC line. Imaging and spatial transcriptomics analysis provided de-tailed insight into the hemanoid architecture, identifying stromal cells and hepatoblasts as potential erythropoiesis-supportive elements. The developmental stage mirrors extraembryonic hematopoiesis. Given the difficulties of accessing these early stages in vivo, our system offers a platform not only for further clinical translation but also for exploring hu-man embryonic blood wave dynamics.