3D bioprinting of collagen-based high-resolution internally perfusable scaffolds for engineering fully biologic tissue systems

Abstract

Organ-on-a-chip and microfluidic systems have improved the translational relevance of in vitro systems; however, current manufacturing approaches impart limitations on materials selection, non-native mechanical properties, geometric complexity, and cell-driven remodeling into functional tissues. Here, we three-dimensionally (3D) bioprint extracellular matrix (ECM) and cells into collagen-based high-resolution internally perfusable scaffolds (CHIPS) that integrate with a vascular and perfusion organ-on-a-chip reactor (VAPOR) to form a complete tissue engineering platform. We improve the fidelity of freeform reversible embedding of suspended hydrogels (FRESH) bioprinting to produce a range of CHIPS designs fabricated in a one-step process. CHIPS exhibit size-dependent permeability of perfused molecules into the surrounding scaffold to support cell viability and migration. Lastly, we implemented multi-material bioprinting to control 3D spatial patterning, ECM composition, cellularization, and material properties to create a glucose-responsive, insulin-secreting pancreatic-like CHIPS with vascular endothelial cadherin⁺ vascular-like networks. Together, CHIPS and VAPOR form a platform technology toward engineering full organ-scale function for disease modeling and cell replacement therapy.