Holographic Display-Based Control for High-Accuracy Photolithography of Cellular Micro-Scaffold With Heterogeneous Architecture

Abstract

Engineered three-dimensional (3D) tissues that replicate composite in-vivo architectures have shown great potential for use in biomedical research. Cell-encapsulated hydrogel micro-scaffolds have been applied widely as basic building blocks to construct these artificial tissues. However, accurate reproduction of heterogeneous hierarchical structures and different regional mechanical properties inside a single integrated micro-scaffold that mimics physiologically relevant complex tissues presents a major challenge. Here, we propose a novel fabrication control algorithm to achieve high-accuracy photolithography of micro-scaffolds that recapitulate the high fidelity of native tissues by adjusting a 3D digital mask using holographic imaging feedback. By performing digital holographic reconstruction to express the hydrogel photocuring process in a matrix form and presetting the curing duration for each discrete point, the 3D digital mask was predefined to represent the required customized micro-scaffold. During fabrication, the UV exposure area was divided into microscaled grids with relatively uniform irradiance to control the photocuring process discretely for every local region in the entire architecture. The holographic imaging feedback allowed the curing duration of each grid to be adjusted in real-time, which enabled accurate reproduction of a 3D construct integrated with different microstructural morphologies and mechanical properties. Finally, PEGDA and GelMA, as typical biomaterials, were used to fabricate the heterogeneous hierarchical micro-scaffold. The structural accuracy was improved from 65 m to 12 m and the Youngs modulus was controlled flexibly in the 27.93.5 to 91.23.5 kPa range. With different local mechanical properties, cell migration in the micro-scaffold from soft to stiff areas is observed successfully.