High-Density, Extrudable Collagen Types I and II Microfiber-Based Inks for Tissue Engineering Applications

Extrusion-based 3D-printing of collagen currently relies almost exclusively on solubilizing collagen, restricting ink formulations to low-density hydrogels that typically contain less than 1% (10 mg/mL) collagen. This low collagen content results in poor mechanical properties, which limit print stability at room temperature and pose significant challenges for engineering scaffolds for high load-bearing tissues. Here, we introduce a method that leverages collagen's electrostatic properties to generate extrudable inks composed of intact, insoluble collagen across a broad range of densities, including 20% (200 mg/mL). These inks preserve native collagen fiber architecture, can be prepared at neutral pH, and allow for room-temperature printing without additional stabilization procedures. Our approach is applicable to both type I collagen and type II collagen, enabling scaffolds to be fabricated with collagen in a form and at contents that more closely reflect those of a variety of tissues. By overcoming limitations associated with soluble, atelocollagen hydrogels, these high-density, insoluble collagen microfiber-based inks provide a new platform for developing physiologically relevant scaffolds for tissue-engineering applications.