The domain of biohybrid robotics attracts significant attention from the scientific community because of its novel approach to combining living and nonliving materials and technical capabilities. Notably, the field intrigues not only natural scientists but also social scientists, ethicists and philosophers, given its distinctive nature and the sociotechnical questions it poses, which transcend disciplinary boundaries. This paper reviews the social, ethical and philosophical dimensions of biohybrid robotics, focusing on recent literature that extends beyond scientific and technical aspects, and presents illustrative cases where the research integrates societal perspectives into its design. The review reveals that, while there are papers addressing ethical debates and various philosophical approaches to understanding living material-integrated robots, there is limited social scientific literature on biohybrid robotics. Importantly, empirical social studies on biohybrid robotics and their communities are lacking. The paper also aims to introduce Science and Technology Studies insights to better situate biohybrid robotics’ potential to shape, and be shaped by, society and its values. By working together and integrating societal values, the biohybrid robotics domain can develop a distinctive path that enriches its foundational growth, enhancing self-understanding through diverse social science perspectives and fostering internal growth.
Advancing in vitro models of immune tissues is a major focus toward answering lingering questions about immunity and developing physiologically relevant drug testing platforms. The composition and structure of the extracellular matrix is an essential consideration in these models as these physical cues can modulate immune cell behavior and ability to mount an immune response. In immune tissues, stromal cells deposit and maintain the extracellular matrix, yet they are often overlooked in existing engineered models. Within, three major strategies for tuning the extracellular matrix in vitro for immune tissue engineering are explored: tunable hydrogel platforms, decellularized tissues, and in-situ deposition of matrix by stromal cells. Overall, the challenge of recapitulating in vivo microenvironments is vast, but the inclusion of stromal cells in the study of extracellular matrix-immune cell dynamics is a vital step forward.
Fluid flow is ubiquitous throughout the immune system. Immune cells exhibit sensitivity to fluid shear stress, altering their activation and behavior in response to the presence, magnitude, and timing of fluid flow. Therefore, understanding how flow regulates the immune response is crucial for understanding the immune system's contribution to homeostasis, disease progression, and therapeutic interventions. Recent developments have indicated Piezo1, a mechanosensitive ion channel protein, is a crucial mechanism for cell sensing and response to shear, but our understanding of how shear impacts immune function is far from complete. Open questions including: how cells respond to acute vs chronic shear stress exposure, how shear influences cell-cell communication, and direct molecular mechanisms require further investigation. In vitro modeling provides one promising approach to fill this gap, and many systems have been recently developed that incorporate flow to investigate the immune response in model organs and disease states. This review discusses recent advances in our understanding of fluid shear stress's impact on immune cell behavior, and we provide a landscape of in vitro models integrating flow and immune cells. To guide future development, we evaluate five critical design considerations: flow directionality, channel cross-section, culture substrate, recirculation strategies, and TEER compatibility.
The translational gap in oncology, particularly in immunotherapy, is largely driven by the inability of traditional preclinical models to accurately represent the dynamic physical and biological aspects of human tumor microenvironment (TME). This review presents the evolution of microphysiological systems, so-called organ-on-a-chip systems from 2021 to 2025 as predictive and analytical tools for immunotherapy efficacy in TME. We highlight advancements in engineered vasculature models that move beyond angiogenesis assays to screen vascular normalization strategies, such as anti-vascular endothelial growth factor and tyrosine kinase inhibitors (TKIs) and dissect immune trafficking mechanisms. Furthermore, we discuss the integration of patient-derived organoids (PDOs) into TME-on-a-chip platform, creating autologous immune organoids that retain donor heterogeneity to predict clinical responses to checkpoint inhibitors and combination therapies. Additional emphasis is placed on the critical shift from static end-point analysis to real-time, noninvasive readouts via integrated biosensors and artificial intelligence-driven high-content analysis, which enable the longitudinal noninvasive tracking of metabolic and physical TME dynamics. Finally, we address the regulatory impact of the 2025 Food and Drug Administration guidance supporting the adoption of non-animal alternatives. In conclusion, we observed how, by recapitulating critical TME factors such as interstitial fluid pressure, hypoxia, and stromal stiffness, these platforms are transitioning from platforms capable of optimizing therapeutic regimens before clinical application.
