Fibrin-mediated delivery of KGF in 2D and 3D models of wound regeneration

We developed 2D and 3D models of wound regeneration to assess the efficacy of fibrin and keratinocyte growth factor (KGF or FGF-7) to accelerate skin reepithelialization. A modified scratch wounding assay in culture was used to study the fibrillar structure of fibrin and its effect on keratinocyte migration. A skin equivalent model of wound healing was utilized to examine the same conditions in 3D. Fibrin accelerated the healing of wounds in 2D and 3D when used at physiologic concentrations (2 - 4 mg/ml). Interestingly, higher fibrinogen concentrations had a deleterious effect in 2D but did not alter the rate of healing in the 3D model. We also evaluated the effects of heparin and fibrillar structure of fibrin gels on the kinetics of KGF release. Fibrin gels were then used to deliver KGF to wounds created in skin equivalents grafted to athymic mice. We found that fibrin-mediated delivery of KGF accelerated reepithelialization and increased vascularization of wounds in vivo. Our results suggest that the structure of fibrin may differentially affect growth factor delivery and keratinocyte migration in 2D vs. 3D models.