Double network microgels based on dextran and fibrin with tunable structural, mechanical, and degradation properties

Colloidal hydrogels, also known as microgels, are promising scaffold materials in the biomedical field. Microgels exhibit high biocompatibility, porosity, and mechanical stability, crucial in supporting cell development. Bio-based polymers, such as fibrin or dextran, are desirable for controlling the properties of microgels. The advantage of using these polymers includes producing degradable microgels that enable the release of active components. In this work, we fabricated fibrin-dextran-methacrylate (dextran-MA) interpenetrating polymer network microgels with tunable porosity, stiffness, and degradation profiles using droplet-based microfluidics. We incorporated fibrin to promote cell growth, while adding dextran-MA ensures improved structural stability of the microgels. By systematically varying the dextran-MA concentrations, we produced fibrin-dextran-MA microgels with a tunable range of stiffness, porosity, and degradation time, highlighting the material's versatility for biomedical applications. In particular, increasing the dextran-MA content reduced pore size, thereby offering a means to control the encapsulation and release of active components. Degradation studies using plasminogen and dextranase revealed that the degradation of the microgels strongly depended on the polymer concentration. This dependency allows controlling the degradation time and the release kinetics of active components, e.g., hepatocyte growth factor (HGF). HGF encapsulated in fibrin microgels was released rapidly through diffusion, while the release from fibrin-dextran microgels was delayed until enzymatic degradation. This delayed degradation of microgels demonstrates the potential to use the microgels for programmable release. Encapsulation of HGF in fibrin and fibrin-dextran-MA microgels promoted the spreading of human mesenchymal stem cells on the microgels, highlighting their potential for personalized Tissue Engineering applications. Our studies reveal that engineered microgels composed of fibrin and dextran-MA can be used as colloidal building blocks to design biomaterials with tailored stiffness, porosity, degradation, and programmed release behavior.