Pengyu Huang

Acute myeloid leukaemia (AML) urgently requires more reliable in vitro platforms for drug evaluation, as existing models often fail to maintain the phenotypic, metabolic, and pharmacologic features of primary leukaemic cells. To address this limitation, we developed a rapidly assembled, screening‐compatible three‐dimensional (3D) bioprinting platform. It encapsulates patient‐derived bone marrow mononuclear cells within a gelatin‐hyaluronic acid hydrogel, whose mechanical properties are tuned to match those of native bone marrow. Within this controlled 3D microenvironment, primary AML cells better maintain an in vivo‐like state, showing enhanced viability, sustained proliferative capacity, preservation of stem‐like subpopulations, and drug responses that more closely mirror clinical behaviour. Transcriptomic profiling further revealed robust activation of MYC target programs and mTORC1 signalling, accompanied by elevated oxidative phosphorylation and glycolytic activity, indicative of the highly proliferative and metabolically active state exhibited by AML cells in vivo. These findings demonstrate that our patient‐specific, 3D bioprinted system provides a high‐fidelity model. This model faithfully recapitulates AML physiology and metabolic features while capturing inter‐patient variability. Consequently, it offers a more reliable and predictive platform for preclinical drug assessment.

The liver is central to drug metabolism and a critical site of disease progression, making vascularized in vitro liver models essential for disease modeling, drug discovery, and mechanistic research. However, recapitulating dynamic in vivo drug responses while maintaining clinical relevance remains a major challenge for bioartificial liver systems. In acute myeloid leukemia (AML), patients frequently develop leukemic liver infiltration and chemotherapy-induced hepatotoxicity, both of which compromise therapeutic efficacy and prognosis. Human-relevant experimental models that dynamically simulate these processes are urgently needed. Here, we developed a dynamic perfusable human vascularized liver module (DPHV-LM), constructed from in vitro–expanded primary human hepatocytes within a perfusable scaffold. Perfusion of AML patient–derived cells reproduced leukemic infiltration of liver tissue. Using the DPHV-LM for drug screening and validating findings in AML mouse models, we identified ammonium glycyrrhizinate (AMGZ) as an agent that reduces cytarabine-induced hepatotoxicity and suppresses leukemic infiltration without impairing antileukemic efficacy. The hepatoprotective trends observed in the DPHV-LM were qualitatively concordant with findings from an independent retrospective clinical cohort. Collectively, these results demonstrate the transplantational potential of this platform for modeling leukemic liver pathology and for the development of hepatoprotective therapeutic strategies.

Three-dimensional (3D) bioprinting is an emerging strategy for constructing tissues and organs in vitro . Here, we achieved long-term expansion of primary mouse hepatocytes using a defined medium and constructed liver tissue using 3D bioprinting. The 3D-printed liver tissue demonstrated several essential liver functions and was able to prolong the survival of mice with acute liver failure due to extreme hepatectomy after in vivo transplantation, and the transplanted artificial liver tissue showed distinct functional partitioning. Overall, our results develop a method for long-term in vitro culture of primary hepatocytes and demonstrate the potential of 3D bio-printed liver tissue for clinical translational applications.

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age‐related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual’s physiological and molecular state, across diverse Chinese cohorts. This Perspective outlines the core objectives, methodological framework and key deliverables of the X-Age Project, including cohort recruitment, standardized sample collection, multimodal data acquisition and clock model development. By integrating interdisciplinary expertise, we aim to provide a practical and scalable platform for understanding aging complexity and heterogeneity, early detection of accelerated aging and evaluation of aging interventions.

The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions.

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro–expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.

X-ray scattering/diffraction tensor tomography techniques are promising methods to acquire the 3D texture information of heterogeneous biological tissues at micrometre resolution. However, the methods suffer from a long overall acquisition time due to multi-dimensional scanning across real and reciprocal space. Here, a new approach is introduced to obtain 3D reciprocal information of each illuminated scanning volume using mathematic modeling, which is equivalent to a physical scanning procedure for collecting the full reciprocal information required for voxel reconstruction. The virtual reciprocal scanning scheme was validated by a simulated 6D wide-angle X-ray diffraction tomography experiment. The theoretical validation of the method represents an important technological advancement for 6D diffraction tensor tomography and a crucial step towards pervasive applications in the characterization of heterogeneous materials.

The construction of bioartificial livers, such as liver organoids, offers significant promise for disease modeling, drug development, and regenerative medicine. However, existing methods for generating liver organoids have limitations, including lengthy and complex processes (taking 6–8 weeks or longer), safety concerns associated with pluripotency, limited functionality of pluripotent stem cell‐derived hepatocytes, and small, highly variable sizes (typically ≈50–500 µm in diameter). Prolonged culture also leads to the formation of necrotic cores, further restricting size and function. In this study, a straightforward and time‐efficient approach is developed for creating rapid self‐assembly mini‐livers (RSALs) within 12 h. Additionally, primary hepatocytes are significantly expanded in vitro for use as seeding cells. RSALs exhibit consistent larger sizes (5.5 mm in diameter), improved cell viability (99%), and enhanced liver functionality. Notably, RSALs are functionally vascularized within 2 weeks post‐transplantation into the mesentery of mice. These authentic hepatocyte‐based RSALs effectively protect mice from 90%‐hepatectomy‐induced liver failure, demonstrating the potential of bioartificial liver‐based therapy.