Off-the-Shelf Granular Microtissue Bioinks: Long-Term Preserved Cellularized Porous Microgels with Enhanced Cell...

Off-the-shelf cellularized products greatly advance the therapeutic practice for tissue engineering and regenerative medicine. However, it remains a challenge to achieve long-term preservation and superior biological outcomes. Here, the cryo-gelation methodology is optimized to develop a cellularized porous microgel platform that allows for long-term cryopreservation on the shelf (up to 14 months) and favors tissue growth due to the presented subvoxel interfaces. The modular granular microtissues serve as an injectable formulation for non-invasive therapy and innovative printable bioinks for precise biofabrication, free of on-site operations on cell isolation and preparation. The internal biomaterial interfaces down to the microtissue building blocks significantly enhance cell growth and function, compared to the conventional bulk counterpart. The ready-to-use potential of months-preserved hMSC-laden modules is demonstrated through subcutaneous injection and critical-sized skull defect repair in rats, which confirms the benefits of subvoxel interfaces for tissue regeneration. These off-the-shelf granular cellularized blocks enable highly accessible and on-demand use in cell-based regenerative medicine.