Thermally reversible hydrogels printing of customizable bio-channels with curvature

Abstract

Replicating intricate bio-channels, akin to expansive vascular networks, offers numerous advantages including self-repair, replacing damaged bio-channels, testing drugs, and biomedical devices. But, crafting multi-sized, editable bio-channels with specific curvatures, particularly using natural polymer-based bio-inks, poses a significant challenge. To address this, this study introduces a temperature-driven indirect printing method, exemplified by the diploic vein. Here, K-carrageenan (kca)-silk fiber (SF)-hyaluronic acid (HA)/hFOB 1.19 (SV40 transfection of human osteoblasts) and kca-collagen-HA/HUVECs (human umbilical vein endothelial cells) are employed to fabricate vascular-like walls and lumens, utilizing their thermoreversible properties to create multi-stage bifurcated lumens. Precise spatial curvature was generated by heating the vascular network wrapped in poly(N-isopropyl acrylamide) (PNIPAAm)-poly(ethylene glycol) diacrylate (PEGDA). Since temperature is specific to the thermal material carrying the cells, the rheological properties of bioinks, modeling temperature parameters, and their impact on printing size was explored. Additionally, mechanical properties and curvature response were characterized to determine the necessary process parameters for achieving the desired size. Ultimately, in vitro bioprinting experiments involving HUVECs and hFOB 1.19 demonstrate cell viability, adhesion, proliferation, and migration within the intraluminal hydrogel scaffold. This approach allows for customizing bio-channel content and controlling curvature programming, providing new prospects for in vitro biochannel production, with potential benefits for pathology research.