Fabrication of channeled scaffolds through polyelectrolyte complex (PEC) printed sacrificial templates for tissue formation

One of the pivotal factors that limit the clinical translation of tissue engineering is the inability to create large volume and complex three-dimensional (3D) tissues, mainly due to the lack of long-range mass transport with many current scaffolds. Here we present a simple yet robust sacrificial strategy to create hierarchical and perfusable microchannel networks within versatile scaffolds via the combination of embedded 3D printing (EB3DP), tunable polyelectrolyte complexes (PEC), and casting methods. The sacrificial templates of PEC filaments (diameter from 120 to 500 μm) with arbitrary 3D configurations were fabricated by EB3DP and then incorporated into various castable matrices (e.g., hydrogels, organic solutions, meltable polymers, etc.). Rapid dissolution of PEC templates within a 2.00 M potassium bromide aqueous solution led to the high fidelity formation of interconnected channels for free mass exchange. The efficacy of such channeled scaffolds for in vitro tissue formation was demonstrated with mouse fibroblasts, showing continuous cell proliferation and ECM deposition. Subcutaneous implantation of channeled silk fibroin (SF) scaffolds with a porosity of 76% could lead to tissue ingrowth as high as 53% in contrast to 5% for those non-channeled controls after 4 weeks. Both histological and immunofluorescence analyses demonstrated that such channeled scaffolds promoted cellularization, vascularization, and host integration along with immunoregulation.