title: Tissue engineering in plastic surgery: a review.
abstract: Novel tissue- and organ-engineering strategies are needed to address the growing need for replacement biological parts. Collective progress in stem cell technology, biomaterials, engineering, and molecular medicine has advanced the state of regenerative medicine, yet many hurdles to clinical translation remain. Plastic surgeons are in an ideal position to capitalize on emerging technologies and will be at the forefront of transitioning basic science research into the clinical reconstructive arena. This review highlights fundamental principles of bioengineering, recent progress in tissue-specific engineering, and future directions for this exciting and rapidly evolving area of medicine.
authors.affiliation: Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Wong
authors.forename: Kristine C
authors.initials: KC
authors.lastname: Rustad
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D006801:Humans; D019651:Plastic Surgery Procedures / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*
references.citation: Sterodimas A, De Faria J, Correa WE, Pitanguy I. Tissue engineering in plastic surgery: An up-to-date review of the current literature. Ann Plast Surg. 2009;62:97–103.
references.citation: Walgenbach KJ, Voigt M, Riabikhin AW, et al. Tissue engineering in plastic reconstructive surgery. Anat Rec. 2001;263:372–378.
references.citation: Gurtner GC, Callaghan MJ, Longaker MT. Progress and potential for regenerative medicine. Annu Rev Med. 2007;58:299–312.
references.citation: Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008;453:314–321.
references.citation: Shieh SJ, Vacanti JP. State-of-the-art tissue engineering: From tissue engineering to organ building. Surgery 2005;137:1–7.
references.citation: Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920–926.
references.citation: Weissman IL. Stem cells: Units of development, units of regeneration, and units in evolution. Cell 2000;100:157–168.
references.citation: Bianco P, Robey PG. Stem cells in tissue engineering. Nature 2001;414:118–121.
references.citation: Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145–1147.
references.citation: Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.
references.citation: Mikkola HK, Orkin SH. The journey of developing hematopoietic stem cells. Development 2006;133:3733–3744.
references.citation: Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.
references.citation: Tepper OM, Capla JM, Galiano RD, et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood 2005;105:1068–1077.
references.citation: Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007.
references.citation: Blanpain C, Fuchs E. Epidermal homeostasis: A balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009;10:207–217.
references.citation: Shi X, Garry DJ. Muscle stem cells in development, regeneration, and disease. Genes Dev. 2006;20:1692–1708.
references.citation: Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev. 2005;85:1373–1416.
references.citation: Gage FH. Mammalian neural stem cells. Science 2000;287:1433–1438.
references.citation: Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872.
references.citation: Saltzman W, Olbricht W. Building drug delivery into tissue engineering. Nat Rev Drug Discov. 2002;1:177–186.
references.citation: Zhang S, Uludağ H. Nanoparticulate systems for growth factor delivery. Pharm Res. 2009;26:1561–1580.
references.citation: Anitua E, Sánchez M, Orive G, Andia I. Delivering growth factors for therapeutics. Trends Pharmacol Sci. 2008;29:37–41.
references.citation: Sinha VR, Trehan A. Biodegradable microspheres for protein delivery. J Control Release 2003;90:261–280.
references.citation: Zhang X, Godbey WT. Viral vectors for gene delivery in tissue engineering. Adv Drug Deliv Rev. 2006;58:515–534.
references.citation: Bonadio J. Tissue engineering via local gene delivery: Update and future prospects for enhancing the technology. Adv Drug Deliv Rev. 2000;44:185–194.
references.citation: Place ES, Evans ND, Stevens MM. Complexity in biomaterials for tissue engineering. Nat Mater. 2009;8:457–470.
references.citation: Chan BP, Leong KW. Scaffolding in tissue engineering: General approaches and tissue-specific considerations. Eur Spine J. 2008;17:467–479.
references.citation: Drury JL, Mooney DJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 2003;24:4337–4351.
references.citation: Furth ME, Atala A, Van Dyke ME. Smart biomaterials design for tissue engineering and regenerative medicine. Biomaterials 2007;28:5068–5073.
references.citation: Nori A, Yim EKF, Chen S, et al. Cell-substrate interactions. In: Principles of Regenerative Medicine. San Diego, Calif: Academic Press; 2008:666–685.
references.citation: Aarabi S, Longaker MT, Gurtner GC. Hypertrophic scar formation following burns and trauma: New approaches to treatment. PLoS Med. 2007;4:e234.
references.citation: Charruyer A, Ghadially R. Stem cells and tissue-engineered skin. Skin Pharmacol Physiol. 2009;22:55–62.
references.citation: Jensen T. Cutaneous gene therapy. Ann Med. 2007;39:108–115.
references.citation: Larcher F, Dellambra E, Rico L, et al. Long-term engraftment of single genetically modified human epidermal holoclones enables safety pre-assessment of cutaneous gene therapy. Mol Ther. 2007;15:1670–1676.
references.citation: Trottier V, Marceau-Fortier G, Germain L, Vincent C, Fradette J. IFATS collection: Using human adipose-derived stem/stromal cells for the production of new skin substitutes. Stem Cells 2008;26:2713–2723.
references.citation: Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663–676.
references.citation: Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007;448:313–317.
references.citation: Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007;448:318–324.
references.citation: Lowry WE, Richter L, Yachechko R, et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA. 2008;105:2883–2888.
references.citation: Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 2007;127:998–1008.
references.citation: Metcalfe AD, Ferguson MW. Bioengineering skin using mechanisms of regeneration and repair. Biomaterials 2007;28:5100–5113.
references.citation: Metcalfe AD, Ferguson MW. Tissue engineering of replacement skin: The crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J R Soc Interface 2007;4:413–437.
references.citation: Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 2009;5:1–13.
references.citation: Macri L, Clark R. Tissue engineering for cutaneous wounds: Selecting the proper time and space for growth factors, cells and the extracellular matrix. Skin Pharmacol Physiol. 2009;22:83–93.
references.citation: Cherubino M, Marra KG. Adipose-derived stem cells for soft tissue reconstruction. Regen Med. 2009;4:109–117.
references.citation: Stosich MS, Moioli EK, Wu JK, et al. Bioengineering strategies to generate vascularized soft tissue grafts with sustained shape. Methods 2009;47:116–121.
references.citation: Gomillion CT, Burg KJ. Stem cells and adipose tissue engineering. Biomaterials 2006;27:6052–6063.
references.citation: Alhadlaq A, Tang M, Mao JJ. Engineered adipose tissue from human mesenchymal stem cells maintains predefined shape and dimension: Implications in soft tissue augmentation and reconstruction. Tissue Eng. 2005;11:556–566.
references.citation: Matsumoto D, Sato K, Gonda K, et al. Cell-assisted lipotransfer: Supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection. Tissue Eng. 2006;12:3375–3382.
references.citation: Bach AD, Beier JP, Stern-Staeter J, Horch RE. Skeletal muscle tissue engineering. J Cell Mol Med. 2004;8:413–422.
references.citation: Bian W, Bursac N. Tissue engineering of functional skeletal muscle: Challenges and recent advances. IEEE Eng Med Biol Mag. 2008;27:109–113.
references.citation: Scime A, Caron AZ, Grenier G. Advances in myogenic cell transplantation and skeletal muscle tissue engineering. Front Biosci. 2009;14:3012–3023.
references.citation: Levenberg S, Rouwkema J, Macdonald M, et al. Engineering vascularized skeletal muscle tissue. Nat Biotechnol. 2005;23:879–884.
references.citation: Boldrin L, Elvassore N, Malerba A, et al. Satellite cells delivered by micro-patterned scaffolds: A new strategy for cell transplantation in muscle diseases. Tissue Eng. 2007;13:253–262.
references.citation: Raghunath J, Salacinski HJ, Sales KM, Butler PE, Seifalian AM. Advancing cartilage tissue engineering: The application of stem cell technology. Curr Opin Biotechnol. 2005;16:503–509.
references.citation: Sharma B, Elisseeff JH. Engineering structurally organized cartilage and bone tissues. Ann Biomed Eng. 2004;32:148–159.
references.citation: Sterodimas A, de Faria J, Correa WE, Pitanguy I. Tissue engineering and auricular reconstruction: A review. J Plast Reconstr Aesthet Surg. 2009;62:447–452.
references.citation: Wescoe KE, Schugar RC, Chu CR, Deasy BM. The role of the biochemical and biophysical environment in chondrogenic stem cell differentiation assays and cartilage tissue engineering. Cell Biochem Biophys. 2008;52:85–102.
references.citation: Getgood A, Brooks R, Fortier L, Rushton N. Articular cartilage tissue engineering: Today's research, tomorrow's practice? J Bone Joint Surg (Br.) 2009;91:565–576.
references.citation: Kuo CK, Li WJ, Mauck RL, Tuan RS. Cartilage tissue engineering: Its potential and uses. Curr Opin Rheumatol. 2006;18:64–73.
references.citation: Chung C, Mesa J, Miller GJ, Randolph MA, Gill TJ, Burdick JA. Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks. Tissue Eng. 2006;12:2665–2673.
references.citation: Shieh SJ, Terada S, Vacanti JP. Tissue engineering auricular reconstruction: In vitro and in vivo studies. Biomaterials 2004;25:1545–1557.
references.citation: Yanaga H, Imai K, Fujimoto T, Yanaga K. Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia. Plast Reconstr Surg. 2009;124:817–825.
references.citation: Service RF. Tissue engineers build new bone. Science 2000;289:1498–1500.
references.citation: Meijer GJ, de Bruijn JD, Koole R, van Bitterswijk CA. Cell-based bone tissue engineering. PLoS Med. 2007;4:e9.
references.citation: El Tamer MK, Reis RL. Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med. 2009;3:327–337.
references.citation: Dupont KM, Sharma K, Stevens HY, Boerckel JD, Garcia AJ, Guldberg RE. Human stem cell delivery for treatment of large segmental bone defects. Proc Natl Acad Sci USA. 2010;107:3305–3310.
references.citation: Siddappa R, Martens A, Doorn J, et al. cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proc Natl Acad Sci USA. 2008;105:7281–7286.
references.citation: Habibovic P, de Groot K. Osteoinductive biomaterials: Properties and relevance in bone repair. J Tissue Eng Regen Med. 2007;1:25–32.
references.citation: El-Ghannam A. Bone reconstruction: From bioceramics to tissue engineering. Expert Rev Med Devices 2005;2:87–101.
references.citation: Cowan CM, Shi YY, Aalami OO, et al. Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol. 2004;22:560–567.
references.citation: Cowan CM, Aalami OO, Shi YY, et al. Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover. Tissue Eng. 2005;11:645–658.
references.citation: Bueno EM, Glowacki J. Cell-free and cell-based approaches for bone regeneration. Nat Rev Rheumatol. 2009;5:685–697.
references.citation: Quarto R, Mastrogiacomo M, Cancedda R, et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med. 2001;344:385–386.
references.citation: Warnke PH, Springer IN, Wiltfang J, et al. Growth and transplantation of a custom vascularised bone graft in a man. Lancet 2004;364:766–770.
references.citation: L'Heureux N, Dusserre N, Marini A, Garrido S, de la Fuente L, McAllister T. Technology insight: The evolution of tissue-engineered vascular grafts. From research to clinical practice. Nat Clin Pract Cardiovasc Med. 2007;4:389–395.
references.citation: Thomas AC, Campbell GR, Campbell JH. Advances in vascular tissue engineering. Cardiovasc Pathol. 2003;12:271–276.
references.citation: Wang X, Lin P, Yao Q, Chen C. Development of small-diameter vascular grafts. World J Surg. 2007;31:682–689.
references.citation: Zhang WJ, Liu W, Cui L, Cao Y. Tissue engineering of blood vessel. J Cell Mol Med. 2007;11:945–957.
references.citation: Levenberg S, Golub JS, Amit M, Itskovich-Eldor J, Langer R. Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci USA. 2002;99:4391–4396.
references.citation: Kaushal S, Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001;7:1035–1040.
references.citation: Shirota T, He H, Yasui H, Matsuda T. Human endothelial progenitor cell-seeded hybrid graft: Proliferative and antithrombogenic potentials in vitro and fabrication processing. Tissue Eng. 2003;9:127–136.
references.citation: Cho SW, Lim SH, Kim IK, et al. Small-diameter blood vessels engineered with bone marrow-derived cells. Ann Surg. 2005;241:506–515.
references.citation: Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK. Tissue engineering: Creation of long-lasting blood vessels. Nature 2004;428:138–139.
references.citation: Matsumura G, Miyagawa-Tomita S, Shin'oka T, Ikada Y, Kurosawa H. First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo. Circulation 2003;108:1729–1734.
references.citation: L'Heureux N, Dusserre N, Konig G, et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nat Med. 2006;12:361–365.
references.citation: L'Heureux N, Pâquet S, Labbé R, Germain L, Auger FA. A completely biological tissue-engineered human blood vessel. FASEB J. 1998;12:47–56.
references.citation: Shin'oka T, Imai Y, Ikada Y. Transplantation of a tissue-engineered pulmonary artery. N Engl J Med. 2001;344:532–533.
references.citation: Engbers-Buijtenhuijs P, Buttafoco L, Poot AA, et al. Biological characterisation of vascular grafts cultured in a bioreactor. Biomaterials 2006;27:2390–2397.
references.citation: Beier JP, Horch RE, Arkudas A, et al. De novo generation of axially vascularized tissue in a large animal model. Microsurgery 2009;29:42–51.
references.citation: Messina A, Bortolotto SK, Cassell OC, Kelly J, Abberton KM, Morrison WA. Generation of a vascularized organoid using skeletal muscle as the inductive source. FASEB J. 2005;19:1570–1572.
references.citation: Chang EI, Bonillas RG, El-ftesi S, et al. Tissue engineering using autologous microcirculatory beds as vascularized bioscaffolds. FASEB J. 2009;23:906–915.
references.citation: Dempsey MP, Hamou C, Michaels JV, et al. Using genetically modified microvascular free flaps to deliver local cancer immunotherapy with minimal systemic toxicity. Plast Reconstr Surg. 2008;121:1541–1553.
references.citation: Ghali S, Dempsey MP, Jones DM, Grogan RH, Butler PE, Gurtner GC. Plastic surgical delivery systems for targeted gene therapy. Ann Plast Surg. 2008;60:323–332.
references.citation: Michaels JV, Dobryansky M, Galiano RD, et al. Ex vivo transduction of microvascular free flaps for localized peptide delivery. Ann Plast Surg. 2004;52:581–584.
references.citation: Li GN, Hoffman-Kim D. Tissue-engineered platforms of axon guidance. Tissue Eng Part B Rev. 2008;14:33–51.
references.citation: Battiston B, Raimondo S, Tos P, et al. Tissue engineering of peripheral nerves. In: International Review of Neurobiology. Vol. 87. New York: Academic Press; 2009:227–249.
references.citation: Terenghi G, Wiberg M, Kingham PJ, et al. Use of stem cells for improving nerve regeneration. International Review of Neurobiology. Vol. 87. New York: Academic Press; 2009:393–403.
references.citation: Subramanian A, Krishnan UM, Sethuraman S. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration. J Biomed Sci. 2009;16:108.
references.citation: Kemp SW, Walsh SK, Midha R. Growth factor and stem cell enhanced conduits in peripheral nerve regeneration and repair. Neurol Res. 2008;30:1030–1038.
references.citation: Tannemaat MR, Verhaagen J, Malessy M. The application of viral vectors to enhance regeneration after peripheral nerve repair. Neurol Res. 2008;30:1039–1046.