Ibrahim Tarik Ozbolat

Cellular alignment through external stimulus offers dynamic control and functional adaptation that static topological or adhesive cues cannot provide. Static alignment strategies can impose defined cellular organization, but these cues are typically fixed after fabrication. By contrast, electric fields provide active bioelectrical cues that can modulate cell orientation, migration, and signaling, making them attractive for regulating cell alignment. However, current electrical‐stimulation platforms still provide limited capability to encode cell organization with microscale spatial precision. Here, we present a new light‐gated bioelectrical stimulation platform enabled by patterned photovoltaic microcell arrays. Those microcells transduce light into localized electric fields for microscale spatial modulation of cell (e.g., fibroblast) behavior pertient to cell orientation and migration. With pulsed light stimulation, the photovoltaic microcell arrays generate a photoelectrical response that can produce local electrical cues associated with pattern‐dependent alignment of fibroblasts perpendicular to the field lines. These results indicate that spatially patterned photovoltaic stimulation can be used not only to stimulate other cell types but also to influence fibroblast alignment and associated molecular responses upon illumination, without wired electrodes. Our study provides a wireless strategy for exploring fibroblast galvanotaxis and suggests a potential approach to guide fibroblast alignment and geometry‐dependent organization, and further tissue morphogenesis.

Microvalve-based bioprinting (MBB) enables precise deposition of bioinks in the form of droplets through the controlled ejection of nanoliter-scale cylindrical ligaments. Despite its increasing use in tissue biofabrication, standardization criteria for assessing bioink printability remain limited. In this study, we present a quantitative printability toolbox for evaluating various bioinks, including fibrinogen, collagen type I, Matrigel, and alginate, in the context of MBB. We systematically analyzed how rheological properties and the contact angle influence ligament formation and droplet ejection. High-speed imaging captured ligament dynamics such as velocity and volume as well as droplet-substrate interactions. The role of Tween 20 (T20) surfactant was further investigated to reduce interfacial aggregation and improve droplet uniformity. Our results revealed viscosity and concentration thresholds specific to each bioink, enabling the construction of a comprehensive printability map correlating bioink properties with ligament stability and droplet printability. This framework provides a practical guide for bioink optimization in MBB towards reproducible fabrication of complex biological structures for biomedical applications.

The field of biofabrication is rapidly evolving, yet it faces persistent challenges, including long manufacturing latency, slow throughput, issues with reproducibility, and scalability limitations. High-throughput biofabrication (HTBF) has emerged as a powerful strategy which is presented here to address these gaps through a structured, three-tier framework. Tier 1 encompasses core HTBF methods, such as multi-modal bioprinting and robotic bioassembly, which enable the rapid fabrication of large, physiologically relevant tissue constructs. Tier 2 comprises assisting platforms, including microfluidics and microphysiological bioreactors, which provide perfusion, mechanical conditioning, multiplexable sensing, and process parallelization. Tier 3 represents HTBF outcomes, including organoids, organ-on-a-chip systems, and engineered tissue grafts that deliver clinically and pharmacologically relevant insights. These advancements enable the development of in-vitro models that streamline drug testing, making it more cost-effective and efficient, while enhancing the accuracy and reliability of preclinical drug evaluation. This review defines HTBF by outlining its core characteristics and framework, presenting insights into recent technological advancements and their applications in regenerative medicine and drug discovery. Additionally, it addresses the regulatory and clinical translation challenges that must be resolved to facilitate the adoption of HTBF in personalized healthcare.

The severe shortage of donor organs and limitations of current disease models highlight the urgent need for transformative strategies in tissue engineering (TE) and regenerative medicine (RM). Bioprinting has emerged as a powerful approach for creating functional tissues and organs, yet current workflows remain labor-intensive, variable, and challenging to scale. The convergence of artificial intelligence (AI), advanced bioprinting technologies, robotics, biosensing, and cutting-edge biological methods is catalyzing the development of self-driving bioprinting laboratories—a fully integrated, autonomous, closed-loop system capable of designing, fabricating, maturing, and assessing living tissue constructs, as well as supporting seamless transplantation, with minimal human intervention. By integrating autonomous cellular farming, on-demand bioink formulation, intelligent optical and digital reconstruction platforms, AI-driven bioprinting, intelligent bioreactors, and robotic transplantation within a sterile, interconnected ecosystem, such platforms can continuously learn, adapt, and optimize workflows, enabling standardized, scalable tissue manufacturing and facilitating a seamless transition from bench to bedside. This perspective outlines the foundational technologies, opportunities, and challenges for realizing self-driving bioprinting, envisioning a future where intelligent, automated platforms transform TE and RM into a scalable, predictive, and clinically integrated discipline at the forefront of precision medicine.

Aligned collagen microstructure is essential for the mechanical and biological function of anisotropic tissues. However, conventional engineering methods often fail to achieve consistent and tunable fiber alignment within complex geometries. In this study, we developed a step‐ladder printing (SLP) approach by incorporating successive segments of channels of variable widths into a custom barrel design, combining controlled extensional flows with 3D bioprinting to enhance collagen fiber alignment. The results revealed that constructs 3D‐printed via SLP demonstrated improved anisotropy of collagen fibers and narrower fiber angle distributions compared to both extrusion‐based bioprinting with a conventional straight nozzle and drop casting methods. Furthermore, SLP effectively guided the directionality of seeded cells, aligning them consistently with underlying collagen fibers. To exemplify the utility of SLP, we built corneal constructs, achieving high transparency and shape fidelity, and articular cartilage constructs, showing mechanical properties within the range of native tissue and supported extracellular matrix production. These results suggest that the SLP approach offers a strategy for fabricating complex anisotropic tissues with integrated fiber alignment and cellular guidance.