Micro/Nano-Scale Cell Printing Precisely Regulates the Microenvironment to Achieve Tissue Functional Regeneration
Release time:
2026-04-13
Imagine if construction workers could not only erect skyscrapers but also, like knitting a sweater, sculpt "nanofibers" at the microscopic scale to guide cell growth. What a scene that would be! Recently, Professor He Jiankang's team at Xi’an Jiaotong University published a groundbreaking review in the top materials science journal Advanced Materials, systematically elaborating on the latest advances in micro/nano-scale 3D bioprinting technology. This technology is striving to break the limitations of macroscopic scaffolds, "writing" cells into the micro/nano world and opening new pathways for tissue regeneration and drug screening.

From "Building Blocks" to "Knitting Sweaters": Breaking the 100-Micron Limit
The sophistication of natural tissues lies in their microstructure: Haversian canals in bone tissue, nanofibers in the cornea, spirally arranged collagen in the myocardium... These micro/nano structures (typically less than 100 micrometers) serve as the "headquarters" regulating cell behavior. However, conventional bioprinting often has a resolution greater than 100 micrometers, allowing only the construction of macroscopic scaffolds—like playing with "building blocks"—and failing to replicate the fine topology of the extracellular matrix (ECM).
Professor He Jiankang's team points out that the rise of micro/nano-scale 3D bioprinting is changing this situation. Through three major technological approaches—photocuring (DLP/TPP), extrusion printing (DIW/EP), and inkjet printing (EHDP/Inkjet)—scientists can now achieve precise construction at submicron or even single-cell resolution. Among them, two-photon polymerization (TPP) uses femtosecond lasers to achieve nanoscale fabrication beyond the diffraction limit, while electrohydrodynamic printing (EHDP) can eject cell-laden fibers as thin as 30 micrometers in diameter.
Mechanics + Topography: Installing a "Navigation System" for Cells
Simply creating tiny structures is not enough; the key lies in how to "direct" the cells. The review highlights the dual regulation of cell fate through "structural signals" and "mechanical signals."
On one hand, shear stress, magnetic fields, or electric fields are used to induce fiber alignment in situ during printing. For example, magnetic field-assisted printing can align magnetic particles in the bioink into chain-like arrangements, guiding stem cells to align and differentiate in specific directions—achieving near-complete muscle fiber regeneration in animal experiments. On the other hand, adjusting hydrogel stiffness can influence cell migration and invasion. This "mechanical-topographical" dual guidance transforms engineered tissues from simple cell aggregates into active organs with physiological functions.
From Regenerative Medicine to "Organoid" Chips
Currently, this technology has demonstrated remarkable potential in multiple fields. In regenerative medicine, skeletal muscle constructs printed with conductive bioink, after eight weeks of implantation, showed electrical signal transmission and paw-print contact area approaching normal levels. In the construction of in vitro models, scientists have used digital light processing (DLP) to print models with liver lobule microstructures, inducing stem cells to form larger multicellular spheroids. Moreover, using 3D droplet printing, they have constructed bilayer cerebral cortex-like tissues and observed functional connections between neurons and host tissues.
Future: AI-Empowered "4D" Biomanufacturing
Despite the promising prospects, challenges remain. How can multi-scale integration of macro- and microstructures be achieved? How can printed tissues dynamically deform during culture (4D printing)? Professor He Jiankang's team envisions that future micro/nano bioprinting will deeply integrate artificial intelligence. AI will be used to optimize printing parameters, discover new bioinks, and even enable real-time monitoring and closed-loop control.
As depicted in the review's future blueprint—from smart bioink preparation to hybrid printing processes and stimulated maturation and development—micro/nano-scale 3D bioprinting is steadily bringing the dream of "custom-made organs" closer to reality.
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