ORIGINAL ARTICLE TISSUE ENGINEERED PREFABRICATED VASCULARIZED FLAPS Kenneth Kian Kwan Oo, MBBS, 1 Wei Chen Ong, MBBS, 2 Annette Hui Chi Ang, MBBS, 1 Dietmar W. Hutmacher, PHD, 3 Luke Kim Siang Tan, MD 1 1 Department of Otolaryngology, Head and Neck Surgery, National University of Singapore, Singapore, Singapore. E-mail: kkkwco@yahoo.com 2 Division of Plastic Surgery, Department of Surgery, National University Hospital, Singapore, Singapore 3 Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore Accepted 10 August 2006 Published online 1 February 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20546 Abstract: Background. Microvascular free tissue transfer has become increasingly popular in the reconstruction of head and neck defects, but it also has its disadvantages. Tissue engineer- ing allows the generation of neo-tissue for implantation, but these tissues are often avascular. We propose to combine tissue-engi- neering techniques together with flap prefabrication techniques to generate a prefabricated vascularized soft tissue flap. Methods. Human dermal fibroblasts (HDFs) labeled with flu- orescein diacetate were static seeded onto polylactic-co-gly- colic 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 morphol- ogy, routine histology, Masson trichrome, and cell viability deter- mined 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 pro- liferated 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 for- mation 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 vascular- ized flap. V V C 2007 Wiley Periodicals, Inc. Head Neck 29: 458– 464, 2007 Keywords: tissue engineering; prefabricated; vascularized; poly- lactic-co-glycolic acid (PLGA) In current clinical practice, there is a constant need for autologous tissue for reconstruction. The pectoralis major flap, 1,2 radial forearm flap, 3,4 and osteocutaneous fibula flap 5 are some of the more commonly used flaps for head and neck reconstruction. The drive by reconstructive sur- geons to provide the best functional and aesthetic outcome for their patients has made microvascu- lar free tissue transfer the preferred reconstruc- tive method. 6 These flaps have superior versatil- ity when compared with regional pedicled flaps, and their reliability 7 makes them increasingly popular. Advances in microsurgical techniques have allowed a wider repertoire of autologous tis- sue transfer. In recent years, perforator flaps like the anterolateral thigh flap 8 have gained popular- Winner of the Resident’s Research presentation at the Singapore Society of Otolaryngology Annual meeting, Singapore, November 2004. Correspondence to: K. K. K. Oo V V C 2007 Wiley Periodicals, Inc. 458 Tissue Engineered Prefabricated Vascularised Flaps HEAD & NECK—DOI 10.1002/hed May 2007