Novel 3D printing technique creates hydrogels that mimic natural tissues

Tissues like skin, arterial walls, or cartilage in our body exhibit a non-linear strain-stiffening behavior (a material's ability to regulate its stiffness based on strain) – which means that they harden exponentially after a threshold level of strain is applied on them. This property of living tissues enables them to perform critical physiological functions during dynamic loading. For instance, collagen fibril arrangements realign in response to mechanical strain, so that the skin does not overextend. This property called ‘hierarchical mechanoresponsiveness’ is inherent to natural tissues. However, synthetic hydrogels, which are used as bioimplants, are unable to achieve this behavior along with other crucial properties like structural complexity and scalability.

In this vein, a research group consisting of Professor Zhilu Yang from Southern Medical University, China, and Professor Xuetao Shi from South China University of Technology, China, has previously shown that an engineered polyvinyl alcohol (PVA)-based hydrogel with short alkyl chains (PVA-Cn-DS) forms stable physically cross-linked networks through solvent/non-solvent-exchange-induced phase separation. These hydrogels demonstrated strain-stiffening behavior similar to biological tissues and formed hierarchical microstructures. However, the current casting methods used to create these hydrogels are restricted to simple geometries like films or sheets, functionally limiting their applications. Additionally, these shapes are incompatible with the complicated architecture required for the 3D printing of these hydrogels. So far, there have been no studies that show how 3D printing methods can fabricate hydrogels that exhibit complex architecture while achieving the natural strain-stiffening behavior.

To address this gap, Prof. Yang and Prof. Shi led a team of researchers to systematically evaluate the printing parameters and ink formulations that enable the creation of structurally complex hydrogels with mechanobiological properties. Their developed the immersion phase separation 3-dimensional printing (IPS 3DP), and their findings were published in Volume 8 of the journal Research on June 17, 2025. Sharing the novelty of their work Prof. Yang states, “Leveraging the unique phase separation dynamics of PVA-Cn-DS, we have developed a novel direct ink writing 3D printing technology called IPS 3DP. The innovation lies in the strategic modulation of solvent exchange kinetics (i.e., the rate at which the solvent [e.g., dimethyl sulfoxide (DMSO)] in the polymer ink diffuses into the coagulation bath [nonsolvent, e.g., water], driving phase separation and gelation) through the optimization of the coagulation bath composition.” This means that by controlling the speed at which the 3D printing ink containing a polymer like DMSO flows into a surrounding liquid bath (usually water, which does not dissolve the ink), the research team was able to achieve structurally complex shapes without affecting their mechanical performance.

By analyzing the combinations of ink concentrations and DMSO content, the researchers were able to establish an empirical relationship (20%-30% DMSO v/v) that optimized solvent exchange rates facilitating appropriate gelation timeframes after ink extrusion. “By leveraging dynamic hydrophobic interactions and solvent exchange kinetics, IPS 3DP achieves multiscale control over pore architectures (5 to 200 μm) and anisotropic microchannels while preserving J-shaped stress–strain curves (fracture stress: ~0.7 MPa; elongation: >1,000%),” explains Prof. Shi while elaborating on their findings. Additionally, the fully cross-linked network formed during the IPS 3DP ensures recyclability with >95% material recovery. This limits material waste when printing defects occur during deposition. PVA-Cn-DS containing materials are biologically inert, and the IPS 3DP ink system provides a flexible platform to improve the functionality of these materials by adding inorganic fillers like hydroxyapatite, carbon nanotubes or copper powder. These materials confer diverse functionalities to biomedical devices, like electrical conductivity enhancement or improved osteogenic induction abilities.

Prof. Yang concludes with the future implications of their work and says, “These advancements establish IPS 3DP as a transformative platform for personalized biomedical implants and adaptive soft robotics,” 

Overall, IPS 3DP presents a unique opportunity to achieve structurally complex and functionally sophisticated biomimetic devices that can be personalized for individual patients.

About the Journal

Launched in 2018, Research is the first journal in the Science Partner Journal (SPJ) program. Research is published by the American Association for the Advancement of Science (AAAS) in association with Science and Technology Review Publishing House. Research publishes fundamental research in the life and physical sciences, as well as important findings or issues in engineering and applied science. The journal publishes original research articles, reviews, perspectives, and editorials and has an impact factor of 10.7 and a CiteScore of 13.3.

Sources: https://doi.org/10.34133/research.0742