Materials Science

4D Printed Programmable Shape-morphing Hydrogels as Intraoperative Self-folding Nerve Conduits for Sutureless Neurorrhaphy

Authors

Abstract

Even as four-dimensional (4D) printing of biomaterials evolves as a fascinating technology to engineer complex and dynamic biomimetic parts, the utility of 4D printed hydrogels in addressing clinical needs in vivo has not been established. In this study, a hydrogel system was engineered from tailored concentrations of alginate and methyl cellulose with defined swelling behaviors, which demonstrated excellent printability in extrusion-based three-dimensional (3D) printing and programmed shape deformations post-printing. Shape deformations of the spatially patterned hydrogels with defined infill angles were computationally predicted for a variety of 3D printed structures, which were subsequently validated experimentally. The gels were further coated with gelatin-rich nanofibers by airbrushing to augment cell attachment and growth. 3D printed hydrogel sheets with pre-programmed infill patterns rapidly self-rolled into hollow 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 a potential to be extended in other areas of regenerative medicine.

Content

Thumbnail image of 4D printing_manuscript.pdf

Supplementary material

Thumbnail image of 4D printing_SI file.pdf
SI text file
Contains supporting information on methodology, materials characterization results, and data on the invitro and in vivo responses.
Thumbnail image of Video V1.mp4
Video 1
Different deformations of a 3D printed trapezoid shape geometry over time controlled by varying the infill angle. V1: Bending along the longer axis when infill angle was 0⁰
Thumbnail image of Video V2.mp4
Video 2
Different deformations of a 3D printed trapezoid shape geometry over time controlled by varying the infill angle. V2: Twisting deformation when infill angle was 45⁰
Thumbnail image of Video V3.mp4
Video 3
Different deformations of a 3D printed trapezoid shape geometry over time controlled by varying the infill angle. V3: Bending along the shorter axis when infill angle was 90⁰.
Thumbnail image of Video V4.mp4
Video 4
Different deformation of a 3D printed plus shape geometry over time controlled by varying the infill angle across arms. V4: Demonstrates real-time bending, which resulted from an infill angle of 90⁰ across each arm.
Thumbnail image of Video V5.mp4
Video 5
Different deformation of a 3D printed plus shape geometry over time controlled by varying the infill angle across arms. V5: Demonstrates real-time twisting, which resulted from infill angles of 45⁰ and -45⁰ across opposite arms.
Thumbnail image of Video V6.mp4
Video 6
Different deformations of a 3D printed petal shape geometry over time controlled by varying the infill angle across arms. V6: Demonstrates real-time bending, which resulted from an infill angle of 90⁰ across each arm.
Thumbnail image of Video V7.mp4
Video 7
Different deformations of a 3D printed petal shape geometry over time controlled by varying the infill angle across arms. V7: Demonstrates real-time twisting, which resulted from an infill angle of 45⁰ across each arm.
Thumbnail image of Video V8.mp4
Video 8
Controlling wing movement of a 3D printed butterfly geometry. V8: Real-time deformation of wing closing, which resulted from an infill angle of 0⁰ placed across each wing.
Thumbnail image of Video V9.mp4
Video 9
Controlling wing movement of a 3D printed butterfly geometry. V9: Twisting movement obtained by infill angle of 45⁰ across each wing.
Thumbnail image of Video V10.mp4
Video 10
A 3D printed hollow rectangle geometry deforming into more complicated geometries. V10: Bending deformation across longer axis caused due to infill angle of 0⁰.
Thumbnail image of Video V11.mp4
Video 11
A 3D printed hollow rectangle geometry deforming into more complicated geometries. V11: Twisting deformation caused due to infill angle of 45⁰.