Biofabrication involves the creation of complex 3D structures using bioinks made of biomaterials or living cells, with advanced light-based techniques, such as two-photon polymerization, digital light processing and volumetric bioprinting, offering advantages in resolution, speed or scalability (see Review by Jason Burdick and colleagues). These methods hold promise for regenerating functional tissues, improving disease modelling, and developing affordable, scalable medical solutions. However, the theoretical resolution limits of these systems remain difficult to achieve with cell-laden constructs, in which light scattering, oxygen inhibition and radical diffusion compromise feature fidelity, as discussed by Yong He and colleagues. Moreover, the relationship between fabrication parameters and cellular responses remains poorly understood. Although increasingly complex structures can be generated at faster speeds, the ability to predict and control cell behaviour within these constructs lags behind.

The recent introduction of dynamic interface printing (DIP)1 represents an innovative approach to addressing long-standing issues of vat polymerization such as material sedimentation and contamination risks. The acoustically modulated air–liquid interface of DIP enables in situ fabrication of high-resolution supportless structures in standard laboratory containers within seconds, overcoming the need for mechanical separation forces that often compromise delicate scaffolds.

The integration of light or photoacoustic waves as a control mechanism extends beyond initial fabrication. As highlighted by Cole DeForest and colleagues, light is an essential tool for manipulating living systems with high spatiotemporal precision. In addition, advanced chemistries have expanded the toolkit for creating dynamic matrices for post-fabrication modification of mechanical properties and biochemical functionalization through light-triggered reactions. Yet, the cytotoxicity of photoinitiators and the generation of radicals during photopolymerization remain concerns, particularly for sustained or sequential modification processes.

Precision in biofabrication is not merely about achieving finer resolution but also about maintaining biological viability, while integrating fidelity and scalability. Sarah Heilshorn and colleagues discuss organoid bioprinting as an exemplar of this integration. Organoids, with their self-organizing capabilities, mimic tissue complexity but have limited scalability and reproducibility. Bioprinting addresses these limitations by enabling spatial control over cell and organoid placement for disease modelling and drug discovery. However, current approaches still struggle to recapitulate the full complexity of organ-specific vascular networks and to maintain metabolic functionality in larger constructs. The challenge of scaling organoids beyond the diffusion limit remains a barrier to creating clinically relevant tissue constructs.

Although scalability, reproducibility and cost-efficiency remain crucial barriers to the clinical translation of printed constructs, biofabrication is already finding its way into commercialized products. For example, Soumya Rahima Benhabbour discusses the use of continuous liquid interface production (CLIP) — a 3D printing technology combining UV light, oxygen and a liquid resin to print computationally aided designed (CAD) objects — to produce intravaginal rings at high manufacturing speed. Notably, the implementation of a stepwise drug incorporation process enables complete separation between device manufacturing and drug incorporation, thus avoiding drug exposure to UV, post-thermal processing (CLIP 3D printing) and high heat or pressure. Similarly, pharmaceuticals can be 3D printed at scale to tailor dosages, thereby preventing under- or overdosing, or to implement controlled-release formulations2.

“Precision in biofabrication is not merely about achieving finer resolution but also about maintaining biological viability, while integrating fidelity and scalability”

From high-resolution tissue models to dynamic, scalable constructs, the field of biofabrication continues to push the boundaries of our capacity to manipulate biological systems and to create ever more intricate structures. These advancements hold the potential to revolutionize treatment strategies and disease modelling, addressing crucial medical needs on a global scale.