Augmentation of adipofascial flaps using the long-term local delivery of insulin and insulin-like growth factor-1

The adipofascial flaps currently described in the literature frequently lac k the volume requirements for reconstructive goals. In this study, the auth ors examined the use of long-term local delivery of insulin and insulin-lik e growth factor-1 (IGF-1) using polylactic-coglycolic acid/polyethylene gly col (PLGA/PEG) microspheres to augment inguinal adipofascial flaps based on the inferior epigastric vessels in the rat. Two flap models, the island na p and the limited dissection flap, were used to demonstrate simultaneous tr eatment and pretreatment modalities, respectively. Experimental groups rece ived 12.5 mg of insulin microspheres (carrying 1 IU of insulin) plus 12.5 m g of IGF-1 microspheres (carrying 2.5 mu g of IGF-1). A group undergoing th e operation only (no treatment with microspheres) and a group treated with blank microspheres (no growth factor) served as external controls for the s urgical procedure and the drug delivery device, respectively. In all groups (n = 5 animals in each), the contralateral flap served as an internal cont rol. Upon harvest on postoperative day 28, the insulin and IGF-l-treated fl aps in both models weighed statistically more than the interval control fla ps and the two external control naps. Likewise, on grass inspection, the ad ipogenic growth factor-treated naps had gr eater volumes than the internal control flap groups and bath of the external control flap groups (operation only and blank microspheres). Other intergroup comparisons suggested the a bsence of a systemic insulin and IGF-1 effect on adiposity. A histomorphome tric analysis suggested (1) that insulin and IGF-1 treatment does not alter flap cell composition and (2) that flap augmentation is secondary to the s timulation of cell proliferation and adipocytic differentiation rather than the hypertrophy of mature adipocytes. Further evidence in favor of cell pr oliferation and differentiation was the discovery of nonanatomic, ectopic f at islands on the pedicle sheath of the treated flaps and the lack of varia tion in cell size distribution among groups. The authors concluded that the long-term local delivery of insulin and IGF-1 with PLGA/PEG microspheres i s an effective method of adipofascial flap augmentation; this method increa ses the number of mature adipocytes rather than increasing the size of pree xisting cells.