Full cell infiltration and thick tissue formation in vivo in tailored electrospun scaffolds

Electrospun (ESP) scaffolds are a promising type of tissue engineering constructs for large defects with limited depth. To form new functional tissue, the scaffolds need to be infiltrated with cells, which will deposit extracellular matrix. However, due to dense fiber packing and small pores, cell and tissue infiltration of ESP scaffolds is limited. Here, we combine two established methods, increasing fiber diameter and co-spinning sacrificial fibers, to create a porous ESP scaffold that allows robust tissue infiltration. Full cell infiltration across 2 mm thick scaffolds is seen 3 weeks after subcutaneous implantation in rats. After 6 weeks, the ESP scaffolds are almost fully filled with tissue. Cell infiltration and tissue formation in this thickness has not been previously achieved. In addition, we propose a novel method for cell seeding to improve cell infiltration and a model to study 3D migration through a fibrous mesh. This easy approach to facilitate cell infiltration further improves previous efforts and could greatly aid tissue engineering approaches utilizing ESP scaffolds.