4D Printed Programmable Shape‐Morphing Hydrogels as Intraoperative Self‐Folding Nerve Conduits for Sutureless Neurorrhaphy

Abstract There are only a few reports of implantable 4D printed biomaterials, most of which exhibit slow deformations rendering them unsuitable for in situ surgical deployment. In this study, a hydrogel system is engineered with defined swelling behaviors, which demonstrated excellent printability in extrusion‐based 3D printing and programmed shape deformations post‐printing. Shape deformations of the spatially patterned hydrogels with defined infill angles are computationally predicted for a variety of 3D printed structures, which are subsequently validated experimentally. The gels are coated with gelatin‐rich nanofibers to augment cell growth. 3D‐printed hydrogel sheets with pre‐programmed infill patterns rapidly self‐rolled into tubes in vivo to serve as nerve‐guiding conduits for repairing sciatic nerve defects in a rat model. These 4D‐printed hydrogels minimized the complexity of surgeries by tightly clamping the resected ends of the nerves to assist in the healing of peripheral nerve damage, as revealed by histological evaluation and functional assessments for up to 45 days. This work demonstrates that 3D‐printed hydrogels can be designed for programmed shape changes by swelling in vivo to yield 4D‐printed tissue constructs for the repair of peripheral nerve damage with the potential to be extended in other areas of regenerative medicine.