How scientists are fabricating brain-like living tissue from structure to intelligence
image: Characteristics of brain complex structure, classification of biomanufacturing methods, key points of functional reconstruction, and application prospects.
Credit: By Ling Wang, Sen Wang, Yingjie Liu, Bowen Zhang, Zhaoyu Pan, Luge Bai, Siqi Yao, Chenrui Zhang, Huangfan Xie, Jiankang He and Dichen Li
Brain, the material foundation of human intelligence, is the most complex tissue in the human body. Brain diseases are among the leading threats to human life. Yet our understanding of their pathogenic mechanisms and the development of effective drugs remains limited, largely due to the lack of accurate brain-like tissue models that replicate the brain’s complex structure and functions. Therefore, constructing brain-like models—in both morphology and function holds significant scientific value for advancing brain science and pathological pharmacology research, representing the frontiers in biomanufacturing.
Published in the International Journal of Extreme Manufacturing, Prof. Dichen Li and Ling Wang’s team from Xi’an Jiaotong University systematically reviewed the frontier developments in the field of bio-manufacturing brain-like living tissue. It is of great significance to understanding the brain, treating brain diseases, and developing brain-like intelligence.
This review outlines the primary requirements and major challenges in building brain-like tissue and summarizes current biomanufacturing methods and strategies. It also highlights recent research on brain repair, development, disease modeling, and brain-inspired computing. The paper ends with a look at future directions, aiming to move from building structures to achieving intelligent functions.
Replicating brain-like tissue in the lab involves mimicking the brain’s complex structure and restoring its function. Key challenges include replicating the multiscale architecture and diverse cell types, reconstructing the physiological microenvironment of the extracellular matrix (ECM), and achieving functional performance that can be evaluated from multiple dimensions.
“Each biomanufacturing method comes with trade-offs,” the researchers explain. Extrusion-based printing supports multiple cell types and is cost-effective, but lacks precision. Electrospinning and photopolymerization achieve microscale accuracy but often focus on single-cell-type structures. Photopolymerization can also pose UV-induced cytotoxic risks. Inkjet printing balances precision and multicellular tissue construction but often results in low cell density. Achieving both fine structure and cell viability remains a central challenge in this field.
To support neural regeneration, scaffolds help treat central nervous system (CNS) injuries by delivering bioactive substances and extracellular vesicles, offering structural support and guiding tissue repair. Traditional fabrication techniques, such as gas foaming, freeze-drying, and solution casting, efficiently produce scaffolds with uniform porosity and oriented structures. However, they lack interconnectivity and fail to integrate active microstructural designs. Electrospinning facilitates bioactive scaffold construction with nanoscale orientation but struggles with precision in cell encapsulation and material distribution. “By integrating cells directly into the scaffold materials, extrusion-based printing enables better control over cell placement and biological cues,” the team notes. These advancements contribute to building vascularized, ECM-like scaffolds for more effective nerve regeneration.
Recent brain-like models aim to replicate specific brain structures and functions in vitro. By combining neural cells, supportive biomaterials, and essential microenvironmental factors, these models enable interactions similar to those in living brain tissue. Current approaches include 2D patterned brain chips, 3D zoned brain models, vascularized models with blood-brain barrier (BBB) features, self-organizing brain organoids, and disease-specific models—each tailored for distinct research needs.
Among these, the brain-like functional neural network model (BFNNM) stands out as a particularly advanced design. It integrates brain-derived cells with high-precision neuroelectronic interfaces and mimics key features of natural brain neural networks, enabling advanced behaviors such as logical reasoning, decision-making, and self-learning, all while consuming less energy compared to conventional computing models.
Despite these developments, no existing model can fully replicate the brain's complexity. “To move forward, we need a better understanding of how material properties, biological signals, and neuronal networks interact,” the researchers explain. They also emphasize the need to improve consistency and reproducibility in the manufacturing process and to establish standardized evaluation methods. “Ultimately, future brain-like systems should not only replicate brain form and function,” said Prof. Ling Wang, “but also move toward intelligent responses, adaptive learning, and deeper integration with sensing and computing technologies.”
About IJEM:
International Journal of Extreme Manufacturing (IF: 16.1, consecutive 1st in the Engineering, Manufacturing category) is a multidisciplinary and double-anonymous peer-reviewed journal uniquely publishing original articles and reviews of the highest quality and impact in the areas related to extreme manufacturing, ranging from fundamentals to process, measurement, and systems, as well as materials, structures, and devices with extreme functionalities.
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