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Tissue-Engineered Breast Reconstruction: Bridging the Gap toward Large-Volume Tissue Engineering in Humans

Findlay, Michael W. M.B.B.S., Ph.D.; Dolderer, Juergen H. M.D.; Trost, Nicholas M.B.B.S.; Craft, Randall O. M.D.; Cao, Yang B.E.(Chem.), Ph.D.; Cooper-White, Justin B.E.(Chem.), Ph.D.; Stevens, Geoffrey B.E.(Chem.), Ph.D.; Morrison, Wayne A. M.D.

Plastic and Reconstructive Surgery: December 2011 - Volume 128 - Issue 6 - p 1206–1215
doi: 10.1097/PRS.0b013e318230c5b2
Experimental: Original Articles

Background: Use of autologous tissue is ideal in breast reconstruction; however, insufficient donor tissue and surgical and donor-site morbidity all limit its use. Tissue engineering could provide replacement tissue, but only if vascularization of large tissue volumes is achievable. The authors sought to upscale their small-animal adipose tissue-engineering models to produce large volumes of tissue in a large animal (i.e., pig).

Methods: Bilateral large-volume (78.5 ml) chambers were inserted subcutaneously in the groin enclosing a fat flap (5 ml) based on the superficial circumflex iliac pedicle for 6 (n = 4), 12 (n = 1), and 22 weeks (n = 2). Right chambers included a poly(L-lactide-co-glycolide) sponge. Other pedicle configurations, including a vascular pedicle alone (n = 2) or in combination with muscle (n = 2) or a free fat graft (n = 2), were investigated in preliminary studies. Serial assessment of tissue growth and vascularization by magnetic resonance imaging was undertaken during growth and correlated with quantitative histomorphometry at chamber removal.

Results: All chambers filled with new tissue by 6 weeks, vascularized by the arteriovenous pedicle. In the fat flap chambers, the initial 5 ml of fat expanded to 25.9 ± 2.4, 39.4 ± 3.9, and 56.5 ml (by magnetic resonance imaging) at 6, 12, and 22 weeks, respectively. Adipose tissue volume was maintained up to 22 weeks after chamber removal (n = 2), including one where the specimen was transferred on its pedicle to an adjacent submammary pocket.

Conclusion: The first clinically relevant volumes of tissue for in situ and remote breast reconstruction have been formed with implications for scaling of existing tissue-engineering models into human trials.

Fitzroy and Parkville, Victoria, Australia

From the O'Brien Institute, the University of Melbourne Department of Surgery; the Department of Medical Imaging, St. Vincent's Hospital Melbourne; and the Department of Chemical and Biomolecular Engineering, the University of Melbourne.

Received for publication February 8, 2011; accepted June 20, 2011.

The first two authors contributed equally to this article.

Disclosure:This study was supported by grant funding from the National Health and Medical Research Council of Australia and the Operational Infrastructure Support Program of the Victoria State Government, Department of Business and Innovation. Additional support was supplied by the Microsurgery Foundation. Dr. Findlay was supported by scholarships from the National Health and Medical Research Council, the Royal Australasian College of Surgeons, and the University of Melbourne. Dr. Dolderer was supported by the German Research Society. There are no other financial interests to declare in relation to the content of this article.

Michael W. Findlay, M.B.B.S., Ph.D.; The O'Brien Institute, St Vincent's Hospital Melbourne, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia,

©2011American Society of Plastic Surgeons