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

Abstract

The 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.