Secretion of FVIII into the bloodstream and correction of coagulation deficiency in hemophilic mice. Grafts were prepared by combining either HA-iECs (n = 5) or HA-FLF8-iECs (n = 9-12) with MSCs in collagen hydrogels followed by subcutaneous injection into immunodeficient hemophilic mice (SCID-f8ko). Tail-tip bleeding assays were performed on day 7. SCID-f8ko and nonhemophilic SCID mice with no implants served as controls. (A) Representative images of the tails after 20 minutes of the bleeding assay for each group. Percentage of body weight loss, used to quantify blood loss (B), and bleeding time (C) were recorded over the duration of the 20-minute bleeding assay with significant lowering of bleeding time and body weight loss percentage to healthy levels in mice with implants containing HA-FLF8-iECs. (D) FVIII activity levels in blood plasma collected on day 7. Levels of circulating FVIII were significantly increased in mice with implants containing HA-FLF8-iECs. Bars represent mean ± SD; **P < .01, ***P < .001.