Thermal Shrinking of Biopolymeric Hydrogels for High Resolution 3D Printing of Kidney Tubules

AbstractThe effective replication of microtubular structures in tissue engineering remains a great challenge. In this study, the temperature‐responsive characteristics of poly(N‐isopropylacrylamide) (pNIPAM) to create intricate, high‐resolution tubular structures through a shrinking mechanism is investigated by exploring 2 thermosensitive hydrogels–gelatin methacryloyl (gelMA) and silk fibroin methacryloyl (silkMA)–combined with pNIPAM. Systematic investigations revealed precise control of shrinking behavior at elevated temperatures (33–37 °C) as a function of polymer concentration. The hydrogel sizes reduce by ≈15% from room temperature (RT) to 33 °C and ≈40% from RT to 37 °C for both hydrogel types. The shrinking affects the mechanical properties, increasing the compressive modulus by ≈2.8‐fold for gelMA‐pNIPAM gels and ≈5.1‐fold for silkMA‐pNIPAM gels at 37 °C. Combined with volumetric printing, these materials achieve resolution enhancements of ≈20% for positive features and ≈70% for negative features, enabling the creation of complex, high‐resolution structures within seconds, with open channels (≈50 µm). GelMA‐pNIPAM hydrogels show better cell compatibility compared to silkMA‐pNIPAM hydrogels, promoting cell adhesion and viability. This study demonstrates the thermosensitive hydrogels' capability to engineer intricate, high‐resolution tubular structures with volumetric printing–an efficient route to fabricate microenvironments mimicking native tissues with potential for developing relevant in vitro models.