Hydrogels to modulate lentivirus delivery in vivo from microporous tissue engineering scaffolds

Numerous strategies to induce tissue regeneration employ scaffolds to create space and present biological cues that promote development. In this report, microporous scaffolds that provide structural support were filled with hydrogels to regulate cell adhesion and migration and were investigated as delivery vehicles for gene therapy vectors in vivo. Porous scaffolds were filled with either lentivirus-entrapped collagen or fibrin hydrogels, both of which support cell adhesion yet have varied rates for degradation and cell infiltration. Empty scaffolds and alginate hydrogels were employed as controls, with the latter not supporting cell infiltration. Hydrogel-filled scaffolds retained the lentivirus more effectively than empty scaffolds, and transgene expression was observed for all scaffold conditions. Empty and fibrin-filled scaffolds had maximal transgene expression in vivo, followed by collagen and alginate, with similar levels. Transduced macrophages and dendritic cells were initially present at the scaffold boundary and adjacent tissue and within the scaffold at later time points for all but the alginate condition. At days 3 and 7, expression was also imaged throughout the spleen and thymus, which may result from cell migration from the implant. These studies demonstrate that hydrogels can modulate gene delivery from scaffolds used in cell transplantation and regenerative medicine.