3D Printing of Gradient Biomimetic Scaffold via Electrochemical Molecular Lock for Tissue Regeneration

Abstract Gradient structures are widely present in tissues. The natural gradient exhibits an accuracy of 10 nm and possesses a four‐level multi‐scale structure (10nm–1cm). The accuracy of biological 3D printing is approximately 5um, which presents huge challenges in simultaneously replicating multi‐scale anisotropy and continuous gradient structures in vitro. Here, a fabrication method termed as electrochemical training of gelatin‐based hydrogel is reported that leverages gradient ion coordination and molecular locking to achieve the rapid assembly of disordered hydrogel to fill this gap. This ETH (electrochemical training hydrogel) scaffold exhibits multi‐scale anisotropic gradient structure from 5nm to 2cm, marking the first successful integration of multi‐scale anisotropy with continuous gradient structures. More importantly, this method constructed a tough gelatin‐based hydrogel scaffold with a strength of 12.67 MPa, which increased by 937 times (13.5 kPa to 12.67 MPa). This study proposes a novel method for constructing bio‐grade gradient hydrogel scaffolds, paving the way for new avenues in engineering biomimetic tissue scaffolds.