The native helical alignment of myocardial fibers is essential for efficient cardiac pumping, yet replicating this architecture at scale remains a major challenge in biofabrication. Here, we present flow-led assembly for spiral hierarchical structures (FLASH), a microfluidic platform that assembles high-cell-density microfibers with a cardiomyocyte-laden collagen/Matrigel core and an endothelial cell-laden alginate sheath. FLASH integrates microfluidic spinning with dual-axis fiber collection on a rotating mandrel, enabling programmable helical alignment with high spatial fidelity. Axial confinement induces cardiomyocyte alignment and functional fiber contraction, while the enzymatic removal of the alginate sheath softens the niche and facilitates endothelial network formation. FLASH achieves > 90% cardiomyocyte alignment, tunable mechanical anisotropy, and a threefold improvement in spatial resolution/time-for-manufacturing (RTM) over conventional bioprinting techniques. Resulting helical ventricular models display coordinated chamber-scale contractions. In a rat myocardial infarction model, FLASH-derived uniaxially aligned cardiac patches improve cardiac function and reduce fibrosis.

DNA offers exceptional information density and long-term stability, yet its practical deployment is limited by destructive readout and the absence of a reusable, physically addressable architecture that connects nanoscale molecular information with macroscale device-level data organization. Here, we present a regenerative Living Disk-Drive system based on thermo-responsive engineered living memory microspheroids (ELMMs), in which data-encoded bacteria are encapsulated as discrete, file-level living storage units. Each ELMM contains a clonal bacterial population carrying both an information plasmid, which encodes 26 × 26 pixel icon payloads and one- to three-color intracellular fluorescent retrieval indices, and a help plasmid that enables CRISPR-Cas12a/λ-Red rewriting of the data sequence and retrieval tag. A lyophilized ELMM database forms the Living Disk, which is coupled to an Optical Retriever and desktop-scale Living Drive for closed-loop retrieval, regeneration, and database replenishment. Released bacteria regrow for downstream readout or rewriting, while a fraction is re-encapsulated into new ELMMs. The tested system retains retrieval, regrowth, and sequence recovery after four months of ambient dry storage and 13 lyophilization-rehydration cycles. Model-based performance estimates are reported only as theoretical architecture-level bounds. These results establish an experimentally bounded yet extensible architecture for physically manageable and regenerative DNA memory.

With rapid advances in regenerative medicine, disease modeling, and personalized medicine, bone organoids have emerged as an innovative and promising platform in tissue engineering. These in vitro generated 3D multicellular constructs recapitulate key structural, cellular, and biochemical features of native bone tissue, offering unique opportunities to study bone development, pathology, and repair. Recent progress has demonstrated the utility of bone organoids in elucidating disease mechanisms, enhancing bone regeneration, and enabling high‐throughput drug screening. This review provides a comprehensive and up‐to‐date overview of bone organoid research published over the past 5 years, covering their definition, characteristic features, fabrication strategies, and applications in bone tissue engineering and bone‐related disease research. We highlight key enabling technologies underlying bone organoid development and systematically compare organoid‐based strategies with conventional bone tissue engineering approaches, with particular emphasis on their ability to simulate the native bone microenvironment. Finally, we discuss current challenges and future development trends of bone organoids, aiming to offer insights that may facilitate their translational application and promote the development of innovative therapeutic strategies for bone regeneration and disease treatment.

Manufacturing graded woodpile structures by Material Extrusion (MEX) requires coordinated control of open porous networks, spatially varying filament geometry, and curved or nonplanar interfaces. Although nonplanar slicing, process-level filament modulation, and adaptive-resolution extrusion have each advanced, they remain only loosely connected for translating continuous structural designs into executable toolpaths for stackable graded architectures. Here, we present a MEX-compatible design-to-manufacturing framework for graded woodpile structures with nonplanar interfaces. Using a rotary rectangular nozzle as the extrusion hardware, the framework converts geometry-field-defined voxel units into feasible executable segment records and G-code through structured-domain design, printable-envelope screening, and calibrated inverse process mapping. The rotary rectangular nozzle achieved an approximately 2.5-fold expansion of the accessible filament-width range and enabled calibrated height-width decoupling; based on this process basis, a continuous-gradient woodpile lattice was fabricated without compensation layers, giving a final build-height error of −2%, while adaptive curved-surface slicing reduced ramp-interface profile roughness by approximately 80%. A meniscus-shaped graded prototype further demonstrates that radial pore-size programming and curved-boundary slicing can be integrated within a single open woodpile lattice, providing a reusable route for fabricating graded woodpile structures with nonplanar interfaces.

Embedded printing is a highly promising approach for creating complex structures within a yield-stress support bath. However, the accurate prediction and control of printability remain fundamental challenges due to the complex interactions between inks and support baths. Here, we present an artificial intelligence (AI)-driven framework that interprets and predicts embedded printability using rheological data. Using a standardized workflow, we extracted 21 rheological descriptors and established 12 indicators to evaluate structural continuity and geometric fidelity. Interpretable machine learning models revealed that direction-dependent defects are governed by the synergistic interplay among ink yield stress, support bath zero-shear viscosity, flow behavior index, and time constant. To enable the prediction of printability in a generalizable manner, we further developed a cascaded neural network, which achieved mean relative prediction errors below 15

Given its exceptional durability and high information density, deoxyribonucleic acid (DNA) has the potential to meet the escalating global demand for data storage if it can be stored efficiently and accessed randomly in exabyte-to-yottabyte-scale databases. Here, this work introduces the Engineered Living Memory Microspheroid (ELMM) as a novel material for DNA data storage, retrieval, and management. This work engineers a plasmid library and devises a random access strategy pairing plasmid function with DNA data in a key-value format. Each DNA segment is integrated with its corresponding plasmid, introduced into bacteria, and encapsulated within matrix material via droplet microfluidics within 5 min. ELMMs can be stored at room temperature following lyophilization and, upon rehydration, each type of ELMM exhibits specific functions expressed by the plasmids, allowing for physical differentiation based on these characteristics. This work demonstrates fluorescent expression as the plasmid function and employs fluorescence-based sorting access image files in a prototype database. By utilizing N optical channels, to retrieve 2N file types, each with a minimum of 10 copies. ELMM offers a digital-to-biological information solution, ensuring the preservation, access, replication, and management of files within large-scale DNA databases.

Myocardial infarction (MI) is a challenging condition that results in scar formation on the ventricular wall, causing myocardial damage and ventricular thinning. Engineered cardiac patches (ECPs) designed to regenerate myocardial tissue have been proposed to repair the ventricular wall and replenish myocardial cells. However, their clinical use is limited by manufacturing and fixation challenges. This study introduces a manufacturing strategy for a composite ECP, which comprises an antiadhesion shell layer, a conductive myocardial tissue, and an exosome-laden microneedle substrate. The ECP can anchor to the infarcted myocardium through its microneedle substrate. Meanwhile, its outer shell prevents nonspecific adhesion, enabling stable and suture-free attachment. Using this microneedle substrate, we applied a 3D-printed ECP in a rat model of post-MI repair. Our results showed that this strategy reduced left ventricular damage, improved cardiac ejection fraction, decreased the fibrotic area, increased ventricular wall thickness, improved microvascular recovery, and thus facilitated the repair of maladaptive ventricular remodeling post-MI. This microneedle substrate holds great promise for use in the fixation of patches during the repair of myocardial tissue and other organs, thereby promoting the clinical application of tissue-engineered patches.

Craniofacial bone defects, particularly those of substantial size, require a significant quantity of cells for effective regeneration. Although developmental engineering strategies using bone mesenchymal stem cells (BMSCs) aggregates have demonstrated potential, they do not fully replicate natural cellular processes. In contrast, periosteal mesenchymal stem cells (PMSCs) exhibit superior efficacy for craniofacial bone regeneration compared to BMSCs. This study aims to engineer periosteum-derived organoids (PDOs) by integrating PMSCs with osteogenic induction centers in 3D-printed polycaprolactone (PCL) scaffolds. Cell condensation was initiated with fibroblast growth factor 8b (FGF8b) and Vitamin C (Vc) to develop a high-density bioink possessing strong osteogenic differentiation capabilities, thereby mimicking osteoblast condensation integral to craniofacial bone repair. Composite scaffolds comprising PCL/beta-TCP and naringin-loaded GelMA hydrogel bio-ink were fabricated, successfully forming calcification centers. Transcriptomic analysis revealed the molecular mechanisms underlying the formation and osteogenic differentiation of PDOs in vitro. This study presents a novel approach to biomimetic periosteum-based bone regeneration in vitro and highlights a promising strategy for scaffold fabrication incorporating calcified centers. These innovations contribute to the ongoing efforts to address the clinical challenge of repairing large craniofacial bone defects, offer valuable insights into the potential of 3D bioprinting for creating biomimetic bone structures, and explore the incorporation of traditional Chinese medicine compounds into bone tissue engineering.

As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies, human disease therapy has witnessed a great leap forward. In particular, three-dimensional (3D) bioprinting stands as a landmark in this setting, by promising the precise integration of biomaterials, cells, and bioactive molecules, thus opening up a novel avenue for tissue/organ regeneration. Curated by the editorial board of Bio-Design and Manufacturing, this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting, by elucidating the intricate challenges encountered in the manufacturing of transplantable organs. We further delve into the translational pathway from scientific research to clinical application, emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control measures. Finally, this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.

Multicolor fluorescent encryption systems that respond to specific stimuli have drawn widespread attention to data storage and encryption due to their low cost and facile data access. However, existing encryption systems are limited by encryption materials, restricting their encryption depth. This study uses DNA molecules as encryption materials that offer exceptional specificity and encryption depth within sequences. With inkjet-printed microarrays on a solid-phase interface, a multicolor fluorescent data storage system based on DNA hybridization and strand displacement is developed, achieving an encryption system with high encryption depth and flexibility. DNA strands, modified with different fluorescent labels, are delivered onto solid-phase interfaces containing a DNA self-assembled monolayer (SAM) via inkjet printing, forming multicolor fluorescent data microarrays. Data storage and encryption are achieved through the hybridization of fluorescent DNA strands for data presentation and interference with the DNA SAM at the interface between the solid phase and droplets. Interference DNA strands can be removed by DNA strand displacement for decryption. The encryption depth of this system is determined by the design of the DNA sequences and the combination of multiple DNA strands, showcasing its outstanding encryption ability. Meanwhile, high-throughput inkjet printing accelerates the data writing process, further enhancing the system efficiency. With DNA solid-phase reaction in inkjet-printed microarrays, this system provides a scalable and robust strategy for high-depth and efficient data encryption.

As commercial spaceflight becomes increasingly accessible, the demand for deep-space exploration and space-based medical solutions is rapidly growing. Space-based three-dimensional (3D) bioprinting provides a transformative platform to fabricate biomimetic tissues in microgravity, enabling precise assessment of spaceflight-induced physiological changes and in situ regenerative interventions during extended missions. Despite progress in modalities such as magnetic levitation and extrusion-based and projection-based printing, space bioprinting remains in its infancy. This perspective examines the unique challenges of the space environment, highlights recent technological advances, and identifies emerging opportunities. We emphasize future directions, including next-generation smart bioinks, integration with microfluidics and macrofluidics, multimodal in situ monitoring, and convergence with artificial intelligence (AI). AI-driven automation, real-time sensing, and adaptive control can enable intelligent, self-sufficient biofabrication platforms for extraterrestrial deployment. Collectively, these efforts will accelerate the transition of space bioprinting from concept to practical application, advancing deep-space medicine, regenerative therapies, and space-based pharmaceutical innovation.

Despite rapid advances in the field of bone tissue engineering, cranial bone defects of critical size remain difficult to repair due to the limited self-regeneration capacity of the bone. Developmental engineering with mesenchymal stem cells (MSCs) aggregates has shown promise for enhanced bone regeneration; however, these MSCs aggregates require extended in vitro osteogenic induction time and lack sufficient vascularization to enable rapid in situ osteogenesis. To address these issues, a novel strategy is introduced for the large-scale generation of prevascularized bone organoids with self-organized vascularization and enhanced osteogenic properties by combining MSCs, human umbilical vein endothelial cells, and osteogenic microparticles. The osteogenic differentiation effects across different microparticles were systematically evaluated and identified graphene oxide as the most effective, which primarily promoted osteogenesis through the focal adhesion and PI3K/Akt pathway. Further, the prevascularized bone organoid-laden hydrogels can be 3D printed into complex tissue constructs with high cell density and osteogenic capacity. In vivo experiments confirmed that this approach promoted rapid vascularized bone tissue formation, achieving effective in situ regeneration and repair of cranial bone defects. This innovative developmental engineering strategy provides a promising, scalable, and effective approach to bone regeneration, advancing developmental tissue engineering for therapeutic applications.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Macrophages are implicated in the fibrotic process, but exhibit remarkable plasticity in the activated immune environment in vivo, presenting significant challenges as therapeutic targets. To explore the influence of macrophages on IPF and develop macrophage-targeted therapies, we engineered a micro-lung chip with a lung epithelium-interstitium tissue unit to establish a controlled immune environment containing only macrophages. We discovered that macrophages exacerbated inflammation and fibrosis by comparing microchips treated with bleomycin (BLM) in the presence and absence of macrophages. Based on the duration of BLM treatment, we established pathological models corresponding to inflammation and fibrosis stages. Transcriptome analysis revealed that activation of the PI3K-AKT signalling pathway facilitates the transition from inflammation to fibrosis. However, LY294002, a PI3K inhibitor, not only suppressed fibrosis and decreased the accumulation of M2 macrophages but also intensified the severity of inflammation. These findings suggest that macrophages play a pivotal role in the potential development at the tissue level. The micro-lung chip co-cultured with macrophages holds significant potential for exploring the pathological progression of IPF and elucidating the mechanisms of anti-fibrotic drugs.

In recent years, engineered conductive myocardium patches have gained increasing attention for their potential in repairing myocardial infarction. However, the traditional fabrication process for these patches often includes the use of toxic conductive monomers and crosslinking agents, along with harsh physical treatments such as low-temperature drying. These elements not only hinder the effective in situ loading of myocardial cells but also limit the efficiency and retention of cell seeding post-fabrication. To address these challenges, we have developed an innovative approach using a granular composite hydrogel, comprised of myocardial cell-laden microgels integrated with an interstitial conductive matrix, capable of being printed into 3D complex electroactive cardiac patches. We used microfluidic technology to encapsulate cardiomyocytes in microgels. Furthermore, we integrated the conductive polymer PEDOT:PSS into a GelMA prepolymer to fabricate a conductive matrix. This matrix was subsequently combined with microgels to form a conductive bioink, which was then utilized for printing a conductive myocardial patch. The results demonstrated that the myocardial cell-laden microgels within the patches maintained robust viability and functionality. Moreover, the patches exhibited electrical conductivity aligned with physiological levels and possessed the requisite mechanical properties for structural support to the infarcted heart. We found that these conductive cell-laden patches significantly improved left ventricular remodelling and heart function post-infarction in a rat model of myocardial infarction. We believe that the design and engineering of conductive cellular myocardium patches represent a significant advancement in the treatment of myocardial infarction.

On-orbit 3D bioprinting offers a more accurate replication of complex tumor environments under space conditions than current 2D and 3D cell models. This technology holds great promise for uncovering regulatory pathways of tumorigenesis and tumor suppression in space, thus accelerating the development of innovative cancer treatments on Earth.

DNA data storage has emerged as a promising information storage technology by encoding information down to base molecules. However, it remains a challenge to structure the DNA data with ease of recording, retrieving, and reading. Here, a primer-disk-enabled hierarchical DNA data storage system is introduced, which allows for the multiple immobilizations of DNA molecules and the generation of corresponding QR codes for retrieving. The primer disk is pre-engineered to present multiple primers, on which encoded DNA molecules with complementary primers can be covalently immobilized on demand via solid-phase PCR. Each DNA file can be retrieved by inkjet printing a fluorescent QR code. A primer disk with up to 10 primers is used. The results show that different DNA files can be subsequently stored on the disk. One can have readily access to the index via fluorescent QR codes and decode information after sequent imaging, convention, and recognition. To this end, the recorded DNA files can be randomly read via solid-phase PCR with sufficient copies of collected DNA for up to 20 reads. Together, this work provides a new DNA data storage system with index and record-many-read-many features, paving the way for the practical use of DNA data storage.

Granular composite (GC) hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties. However, the lack of comprehensive design guidelines has limited their optimal engineering, as the factors influencing their mechanical performance and printability remain largely unexamined. In this study, we developed GC hydrogels by integrating microgels with interstitial matrices of photocrosslinkable gelatin methacrylate (GelMA). We utilized confocal microscopy and nanoindentation analyses to investigate the spatial distribution and mechanical behavior of these hydrogels. Our findings indicate that the mechanical and rheological properties of GC hydrogels can be precisely tailored by adjusting the volume fraction and size of the microgels. Furthermore, hydrogen bonds were identified as significant contributors to compressive performance, although they had minimal effect on cyclic mechanical behavior. Compared to bulk GelMA hydrogels, GC hydrogels demonstrated enhanced printability and remarkable superelasticity. As a proof of concept, we illustrated their dual printability in embedded printing to create prosthetic liver models for preoperative planning. This study provides valuable insights into the design and optimization of GC hydrogels for advanced biomedical applications.

The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine. Currently, existing in vitro tumor models often do not accurately replicate the human gastric cancer environment and are unsuitable for high-throughput therapeutic drug screening. In this study, droplet microfluidic technology is employed to create novel gastric cancer assembloids by encapsulating patient-derived xenograft gastric cancer cells and patient stromal cells in Gelatin methacryloyl (GelMA)-Gelatin-Matrigel microgels. The usage of GelMA-Gelatin-Matrigel composite hydrogel effectively alleviated cell aggregation and sedimentation during the assembly process, allowing for the handling of large volumes of cell-laden hydrogel and the uniform generation of assembloids in a high-throughput manner. Notably, the patient-derived xenograft assembloids exhibited high consistency with primary tumors at both transcriptomic and histological levels, and can be efficiently scaled up for preclinical drug screening efforts. Furthermore, the drug screening results clearly demonstrated that the in vitro assembloid model closely mirrored in vivo drug responses. Thus, these findings suggest that gastric cancer assembloids, which effectively replicate the in vivo tumor microenvironment, show promise for enabling more precise high-throughput drug screening and predicting the clinical outcomes of various drugs.

Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), β-tricalcium phosphate (β-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.

Three-dimensional (3D) bioprinting, which has been applied in tissue engineering and regenerative medicine, uses biomaterials, cells, and other essential components to manufacture organs and tissues with specific biological functions and complex structures. Over the past 30 years, researchers have developed new 3D bioprinting technologies with improved manufacturing capabilities and expanded applications. Chinese research teams contributed significantly to this process. In this paper, we first reviewed the development history and major milestones in 3D bioprinting, categorizing them into two main strategies: "biomaterial-based indirect assembly" and "living cell-based direct assembly". This review further delved into the technical principles, recent advancements, advantages, disadvantages, and applications of each type of bioprinting technology. Finally, the challenges and future directions of 3D bioprinting were summarized to guide future research in China and foster advancements in this dynamic field.