4D Printed Hydrogel Expanders for Personalized and Accelerated Soft Tissue Regeneration

Controllable tissue expansion is critical in regenerative medicine to address skin or mucosal defects. Tissue expanders based on isotropic water filling or swelling offer a clinical solution but face challenges in addressing individual anatomical complexities. Here, a 4D printing biocompatible hydrogel expander with customizable designs is reported. Water-swellable polymer sheets with non-swellable elastomer frameworks are synthesized via digital photocuring. The sheets buckle upon adsorption of tissue fluids to execute anisotropic and programmable morphing, forming predesigned 3D structures with time as the fourth dimension for the shape changing. With an initial thickness of 1.0 mm, which is remarkably thinner than previous devices (typically 3-5 mm), the expander enabled minimally invasive implantation in the rat scalp. After 5 days' implantation, the skin area and weight respectively increase to two and three folds without tissue damage, illustrating that the buckling-based strategy provides a safer yet accelerated expansion effect over previous devices. RNA sequencing indicates that the buckling-induced regeneration involving epithelial-to-mesenchymal transition (EMT) may be affected by the PI3K-AKT pathway. This work provides an inspiring strategy for personalized regeneration medicine.