AbstractBackground.Microvascular free tissue transfer has become increasingly popular in the reconstruction of head and neck defects, but it also has its disadvantages. Tissue engineering allows the generation of neo‐tissue for implantation, but these tissues are often avascular. We propose to combine tissue‐engineering techniques together with flap prefabrication techniques to generate a prefabricated vascularized soft tissue flap.Methods.Human dermal fibroblasts (HDFs) labeled with fluorescein diacetate were static seeded onto polylactic‐co‐glycolic acid‐collagen (PLGA‐c) mesh. Controls were plain PLGA‐c mesh. The femoral artery and vein of the nude rat was ligated and used as a vascular carrier for the constructs. After 4 weeks of implantation, the constructs were assessed by gross morphology, routine histology, Masson trichrome, and cell viability determined by green fluorescence.Results.All the constructs maintained their initial shape and dimensions. Angiogenesis was evident in all the constructs with neo‐capillary formation within the PLGA‐c mesh seen. HDFs proliferated and filled the interyarn spaces of the PLGA‐c mesh, while unseeded PLGA‐c mesh remained relatively acellular. Cell tracer study indicated that the seeded HDFs remained viable and closely associated to remaining PLGA‐c fibers. Collagen formation was more abundant in the constructs seeded with HDFs.Conclusions.PLGA‐c, enveloped by a cell sheet composed of fibroblasts, can serve as a suitable scaffold for generation of a soft tissue flap. A ligated arteriovenous pedicle can serve as a vascular carrier for the generation of a tissue engineered vascularized flap. © 2007 Wiley Periodicals, Inc. Head Neck 2007