Multi‐Material Digital Light Processing (DLP) Bioprinting of Heterogeneous Hydrogel Constructs with Perfusable Networks

Abstract The challenges of replicating the complex mechanical and structural diversity of natural tissues in vitro by leveraging multi‐material digital light processing (DLP) bioprinting are addressed. This technique utilizes PEGDA‐AAm bio‐ink to develop multi‐component, cell‐laden hydrogel constructs with varying moduli. These constructs not only possess heterogeneous mechanical properties but also feature complex architectures and precisely engineered surface microstructures. The hydrogel microfluidic chips are successfully fabricated with perfusable microchannels, embedding various cell types within the matrix. This approach enables the bioprinting of intricate cell‐laden structures with unique surface topologies, such as spiral grooves and triply periodic minimal surfaces (TPMS), which effectively influence cell alignment, spreading, and migration. By integrating various cell‐laden PA hydrogels, the diverse mechanical moduli of biological tissues, including bone, liver lobules, and vascular networks are replicated. This technique ensures high‐fidelity differentiation between cell types and regions. These findings provide valuable insights into the impact of substrate modulus and structure on cell behavior, underscoring the potential of multi‐component, multi‐modulus hydrogel constructs in creating sophisticated structures with custom‐tailored mechanical properties. This study significantly advances the field by demonstrating the feasibility and effectiveness of multi‐material DLP bioprinting in developing complex, functionally relevant tissue models for tissue engineering and regenerative medicine.