Tunable Microgel-Templated Porogel (MTP) Bioink for 3D Bioprinting Applications

Micropores are essential for tissue engineering to ensure adequate mass transportation for embedded cells. Despite the considerable progress made by advanced 3D bioprinting technologies, it remains challenging to engineer micropores of 100 µm or smaller in cell-laden constructs. Here, a microgel-templated porogel (MTP) bioink platform is reported to introduce controlled microporosity in 3D bioprinted hydrogels in the presence of living cells. Templated gelatin microgels are fabricated with varied sizes (≈10, ≈45, and ≈100 µm) and mixed with photo-crosslinkable formulations to make composite MTP bioinks. The addition of microgels significantly enhances the shear-thinning and self-healing viscoelastic properties and thus the printability of bioinks with cell densities up to 1 × 10⁸ mL^-1 in matrix. Consistent printability is achieved for a series of MTP bioinks based on different component ratios and matrix materials. After photo-crosslinking the matrix phase, the templated microgels dissociated and diffused under physiological conditions, resulting in corresponding micropores in situ. When embedding osteoblast-like cells in the matrix phase, the MTP bioinks support higher metabolic activity and more uniform mineral formation than bulk gel controls. The approach provides a facile strategy to engineer precise micropores in 3D printed structures to compensate for the limited resolution of current bioprinting approaches.