Photocrosslinked Silk Fibroin Microgel Scaffolds for Biomedical Applications

Silk fibroin hydrogels are extensively explored for tissue engineering and regenerative medicine as an artificial extracellular matrix (ECM) that can support tissue growth. However, the nanometer pore size of hydrogels limits adequate cell, tissue, and vascular infiltration. Microgel scaffolds are an emerging class of microporous biomaterials formed by annealing small microscale hydrogels (microgels) into a 3D construct. In this work, silk microgels are generated using a microfluidic device that allows tuning of the microgel diameter (100-400 mu m) and are stabilized via visible light-initiated photo-crosslinking of native tyrosine residues in silk. Microgels are then covalently annealed using silk solution as glue and the same cytocompatible visible light-initiated crosslinking to form microgel scaffolds. Unlike the nano-porosity of bulk photo-crosslinked silk hydrogels, the microgel scaffolds have an average pore diameter of 29 +/- 17 or 192 +/- 81 mu m depending on the microgel size, with enhanced mechanical properties compared to bulk hydrogels. This microporosity supports enhanced cell spreading and proliferation in vitro and increases scaffold remodeling in vivo, encouraging improved tissue infiltration and matrix deposition. The microgel size and material format also affect inflammatory responses in vivo. This work demonstrates that silk microgels and microgel scaffolds are promising candidates for tissue engineering and regenerative medicine applications. To address limited cell, tissue, and vascular infiltration associated with nano-porous hydrogels, spherical silk microgels of tunable diameter and annealed microgel scaffolds are developed using photo-initiated crosslinking of native tyrosines in silk. Microgel scaffolds has micro-scale porosity and supported improved cell, tissue, and blood vessel infiltration in vitro and in vivo, and microgel properties modulated inflammatory responses to silk implants. image