Microgel-Based Hierarchical Porous Hydrogel Patch with Adhesion and Resilience for Myocardial Infarction

While there has been considerable success in the 3D bioprinting of hydrogel scaffolds for tissue engineering, the application of traditional centimeter-scale bulk hydrogels with a dense internal nanoscale network structure remains a particular challenge. Here, we present a microgel-based modular fabrication strategy to engineer programmable hierarchically porous microgel-based hydrogel patches (HPMPs). This strategy generates porous microgels with adjustable porosity and bio/cytocompatibility via gas-shearing microfluidics integrated with an aqueous two-phase system, exhibiting precise model structural fidelity, synergistic tissue adhesion, and architectural resilience. Additionally, the interconnected hierarchical porous structure of HPMP enables rapid formation of functional vascular networks in vitro. To demonstrate the broad biomedical applicability of our modular bioprinting platform, we implemented this strategy in myocardial infarction treatment. We successfully validated the application-driven requirements via iPSC-laden porous microgels directing cardiomyocyte differentiation and functional maturity. HPMP with Janus-structured unilateral adhesiveness is conducive to preventing chest adhesions and cellular unilateral proliferation, migration, and angiogenesis in vivo. This microgel-based modular fabrication strategy establishes a promising platform for targeted cardiac repair, further promoting the development of tissue engineering and regenerative medicine.