An Approach for Fabricating Hierarchically Porous Cell‐Laden Constructs Utilizing a Highly Porous Collagen‐Bioink

Abstract

In bioprinting procedures, bioinks typically comprise hydrogels, necessitating a balance between printability and bioactivity. Achieving good printability requires a relatively high hydrogel viscosity, but this can reduce bioactivity due to poor cell‐to‐cell interactions of the encapsulated cells. Therefore, developing hydrogels with excellent printability and bioactivity is a significant challenge in bioprinting. Here, a collagen‐based bioink with excellent printability and bioactivity is developed. The bioink is prepared through a two‐step process: first, by subjecting the bioink to whipping to create a non‐homogeneous porous structure, and subsequently, by employing centrifugation to refine this porous structure into a uniform and relatively smaller microscale porous structure (with a specific diameter of 15.7 ± 9.2 µm). Using the designed bioink, a hierarchical porous structure is fabricated without any special equipment or supporting/sacrificing materials. To demonstrate the feasibility of the collagen bioink laden with human adipose stem cells, a hierarchical cell construct is fabricated using a bioprinter. The construct exhibits significantly enhanced cellular activities and superior osteogenic differentiation compared to the bioprinted cell constructs using normal collagen bioink. These findings suggest that collagen‐based bioinks, which are both printable and bioactive, hold significant promise for extensive utilization in a variety of tissue regeneration applications.