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Handchir Mikrochir Plast Chir 2018; 50(02): 83-92
DOI: 10.1055/s-0043-115117
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Tissue Engineering von Fettgewebe mittels bioabbaubaren Biomaterialien zur Weichteildefektdeckung

Tissue engineering of adipose tissue with biodegradable biomaterials for soft tissue reconstruction
Silvan Klein   *
1   Universitätsklinikum Regensburg, Zentrum für Plastische, Hand- und Wiederherstellungschirurgie
,
Thiha Aung   *
1   Universitätsklinikum Regensburg, Zentrum für Plastische, Hand- und Wiederherstellungschirurgie
,
Robert Michael Haas
2   BG-Unfallklinik, Eberhard Karls Universität Tübingen, Klinik für Hand, Plastische, Rekonstruktive und Verbrennungschirurgie
,
Fabian Medved
2   BG-Unfallklinik, Eberhard Karls Universität Tübingen, Klinik für Hand, Plastische, Rekonstruktive und Verbrennungschirurgie
,
Stefan M. Schiller
3   Albert-Ludwigs Universität Freiburg, Freiburg Institute for Advanced Studies (FRIAS), Center for Biological Systems Analysis (ZBSA)
,
Oliver Felthaus
1   Universitätsklinikum Regensburg, Zentrum für Plastische, Hand- und Wiederherstellungschirurgie
,
Jürgen H. Dolderer
1   Universitätsklinikum Regensburg, Zentrum für Plastische, Hand- und Wiederherstellungschirurgie
› Author Affiliations
Further Information

Publication History

02/24/2017

05/04/2017

Publication Date:
19 April 2018 (online)

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Zusammenfassung

Bestehende Weichteildefekte nach Unfallverletzungen, onkologischen Tumorresektionen, kongenitalen Anomalien oder chronischen Wunden stellen eine zentrale Herausforderung in der rekonstruktiven Chirurgie dar. Der derzeitige Goldstandard in der Therapie von Gewebedefekten besteht in der Gewebetrans plantation in Form von freien oder lokalen Lappenplastiken. Limitierend ist jedoch die unumgängliche Morbidität an der Spenderstelle nach dem Gewebetransfer. Vor diesem Hintergrund wurden in den letzten Jahren aufgrund der günstigen Gewebetextur und hohen Plastizität große Anstrengungen im Bereich des Tissue Engineerings von vaskularisierten, langzeitstabilen autologen Fettgewebskonstrukten unternommen. Dabei stellt der enge Zusammenhang von Adipogenese und Angiogenese eine entscheidende Hürde in der de novo Erzeugung von Fettgewebe dar. Eine besondere Rolle kommt hierbei bioabbaubaren Biomaterialien (Scaffolds) als Trägereinheiten für Zellen und der damit verbundenen Zell-Matrix-Interaktion zu. Ein ideales Biomaterial sollte die Zellproliferation, -adhäsion und -differenzierung unterstützen, und gleichzeitig unbedenklich in seiner Biokompatibilität sein. Die vorliegende Übersichtsarbeit gewährt einen Überblick über derzeitige Ansätze des Tissue Engineerings von Fettgewebe vor dem Hintergrund der aktuell verfügbaren Evidenz.

Die Problematiken bisheriger Modelle sind einerseits hohe Resorptionsraten der gezüchteten Gewebekonstrukte und andererseits der fehlende Nachweis von klinisch relevanten Gewebevolumina. Das Tissue Engineering von Fettgewebe in einem Wachtumskammermodell in Kombination mit Scaffolds bietet eine weitere Möglichkeit zur in vivo Gewebezüchtung. Hier zeigen aktuelle Ergebnisse, dass eine de novo Fettgewebezüchtung mit klinisch relevanten und langzeitstabilen Volumina in vivo möglich ist. Dieses Modell besitzt, unserer Auffassung nach, das Potential die Therapie großer Weichteildefekte signifikant zu verbessern.

Abstract

Soft tissue defects resulting from injuries, tumor resection, congenital anomalies or chronic wounds pose a great challenge to reconstructive surgery. The current gold standard in therapy of such defects is the tissue transplantation in terms of free or local flaps. Unfortunately, donor site morbidity remains a considerable risk of flap surgery. Therefore, tissue engineering of autologous vascularized long term stable adipose tissue constructs could enrich the therapeutic possibilities of soft tissue defects. De novo adipose tissue growing requires fundamental knowledge about this kind of tissue and its synthesis, closely linked to angiogenesis. Bioresorbable biomaterials (scaffolds) are of crucial importance for adipose tissue engineering. Simulation or replacement of extracellular matrix for tissue growth by scaffold application requires a profound understanding of cell-matrix interactions. A proper biomaterial should be capable of supporting cell adherence, proliferation and differentiation. Important features are biocompatibility and resorption without toxic metabolites. In this review, various scaffold materials are discussed and novel achievements are presented. Persisting problems of de novo adipose tissue formation are high resorption rates and small tissue volumes of adipose constructs. Adipose tissue formation in a tissue engineering chamber is an additional possibility for in vivo tissue engineering. Recent studies proof that long term stable de novo adipose tissue formation of clinically relevant tissue volumes is possible. This method, in our opinion, has the potential to improve therapeutic strategies of soft tissue defects significantly.

Schlüsselwörter

Tissue engineering - Biomaterialien - Fettgewebe - Weichteildefekt - Rekonstruktive Chirurgie

Key words

tissue engineering - biomaterials - adipose tissue - soft tissue defect - reconstructive surgery

Fußnote

* S. Klein und T. Aung haben beide zu gleichen Teilen beigetragen


 

  • Literatur

  • 1 Gooden MA, Gentile AT, Mills JL. et al. Free tissue transfer to extend the limits of limb salvage for lower extremity tissue loss. Am. J. Surg 1997; 174: 644-8 discussion 648–9
    CrossrefPubMedGoogle Scholar
  • 2 Patrick CW. Tissue engineering strategies for adipose tissue repair. Anat. Rec 2001; 263: 361-366
    CrossrefPubMedGoogle Scholar
  • 3 Pallua N, Magnus Noah E. The tunneled supraclavicular island flap: an optimized technique for head and neck reconstruction. Plast. Reconstr. Surg 2000; 105: 842-51 discussion 852–4
    CrossrefPubMedGoogle Scholar
  • 4 Czerny V. Plastischer Ersatz der Brustdrüse durch ein Lipom Zentralbl Chir. 1895 27. 72
    PubMedGoogle Scholar
  • 5 Beahm EK, Walton RL, Patrick CW. Progress in adipose tissue construct development. Clin Plast Surg 2003; 30: 547-58 viii
    CrossrefPubMedGoogle Scholar
  • 6 Neuber G. Fetttransplantation. Verhandlungen der Deutschen Gesellschaft für Chirurgie. 1893 22. 66
    PubMedGoogle Scholar
  • 7 Prantl L.. et al. Aktuelle Erkenntnisse zur Eigenfett Transplantation anhand der neue Leitlinie „Autologe Fetttransplantation“. Handchirurgie· Mikrochirurgie· Plastische Chirurgie 2016; 48 (06) 330-336
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Walton RL, Beahm EK, Wu L. De novo adipose formation in a vascularized engineered construct. Microsurgery 2004; 24: 378-384
    CrossrefPubMedGoogle Scholar
  • 9 Hahn P, Novak M. Development of brown and white adipose tissue. J. Lipid Res 1975; 16: 79-91
    PubMedGoogle Scholar
  • 10 Wu J, Boström P, Sparks LM. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150: 366-376
    CrossrefPubMedGoogle Scholar
  • 11 Trayhurn P, Wood IS . . Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br. J. Nutr 2004; 92: 347-355
    CrossrefPubMedGoogle Scholar
  • 12 Cao Y. Angiogenesis modulates adipogenesis and obesity. J. Clin. Invest 2007; 117: 2362-2368
    CrossrefPubMedGoogle Scholar
  • 13 Dolderer JH, Medved F, Haas RM. et al. Angiogenese und Vaskularisation beim Tissue Engineering von Fettgewebe. Handchir Mikrochir Plast Chir 2013; 45: 99-107
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Nakajima I, Yamaguchi T, Ozutsumi K. et al. Adipose tissue extracellular matrix: newly organized by adipocytes during differentiation. Differentiation 1998; 63: 193-200
    CrossrefPubMedGoogle Scholar
  • 15 Tang W, Zeve D, Suh JM. et al. White fat progenitor cells reside in the adipose vasculature. Science 2008; 322: 583-586
    CrossrefPubMedGoogle Scholar
  • 16 Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol 2006; 7: 885-896
    CrossrefPubMedGoogle Scholar
  • 17 Crandall DL, Hausman GJ, Kral JG. A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. Microcirculation 1997; 4: 211-232
    CrossrefPubMedGoogle Scholar
  • 18 Hausman GJ, Kauffman RG. The histology of developing porcine adipose tissue. J. Anim. Sci. 1986; 63: 642-658
    CrossrefPubMedGoogle Scholar
  • 19 Carmeliet P. Angiogenesis in health and disease. Nat. Med 2003; 9: 653-660
    CrossrefPubMedGoogle Scholar
  • 20 Jain RK. Molecular regulation of vessel maturation. Nat. Med. 2003; 9: 685-693
    CrossrefPubMedGoogle Scholar
  • 21 von Heimburg D, Zachariah S, Heschel I. et al. Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo. Biomaterials 2001; 22: 429-438
    CrossrefPubMedGoogle Scholar
  • 22 Kaewsuwan S, Song SY, Kim JH. et al. Mimicking the functional niche of adipose-derived stem cells for regenerative medicine. Expert Opin Biol Ther 2012; 12: 1575-1588
    CrossrefPubMedGoogle Scholar
  • 23 Walton RL, Beahm EK, Wu L. De novo adipose formation in a vascularized engineered construct. Microsurgery 2004; 24: 378-384
    CrossrefPubMedGoogle Scholar
  • 24 Tabata Y, Miyao M, Inamoto T. et al. De novo formation of adipose tissue by controlled release of basic fibroblast growth factor. Tissue Eng 2000; 6: 279-289
    CrossrefPubMedGoogle Scholar
  • 25 Yuksel E, Weinfeld AB, Cleek R. et al. Augmentation of adipofascial flaps using the long-term local delivery of insulin and insulin-like growth factor-1. Plast. Reconstr. Surg 2000; 106: 373-382
    CrossrefPubMedGoogle Scholar
  • 26 Katz AJ, Llull R, Hedrick MH. et al. Emerging approaches to the tissue engineering of fat. Clin Plast Surg 1999; 26: 587-603 viii
    PubMedGoogle Scholar
  • 27 Yuksel E, Weinfeld AB, Cleek R. et al. Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres. Plast. Reconstr. Surg 2000; 105: 1712-1720
    CrossrefPubMedGoogle Scholar
  • 28 Cao Y, Mitchell G, Messina A. et al. The influence of architecture on degradation and tissue ingrowth into three-dimensional poly(lactic-co-glycolic acid) scaffolds in vitro and in vivo. Biomaterials 2006; 27: 2854-2864
    CrossrefPubMedGoogle Scholar
  • 29 Lavik E, Langer R. Tissue engineering: current state and perspectives. Appl. Microbiol. Biotechnol 2004; 65: 1-8
    PubMedGoogle Scholar
  • 30 Hernández A, Reyes R, Sánchez E. et al. In vivo osteogenic response to different ratios of BMP-2 and VEGF released from a biodegradable porous system. J Biomed Mater Res A 2012; 100: 2382-2391
    PubMedGoogle Scholar
  • 31 Weiser B, Prantl L, Schubert TEO. et al. In vivo development and long-term survival of engineered adipose tissue depend on in vitro precultivation strategy. Tissue Eng Part A 2008; 14: 275-284
    PubMedGoogle Scholar
  • 32 Zhou C, Shi Q, Guo W. et al. Electrospun bio-nanocomposite scaffolds for bone tissue engineering by cellulose nanocrystals reinforcing maleic anhydride grafted PLA. ACS Appl Mater Interfaces 2013; 5: 3847-3854
    CrossrefPubMedGoogle Scholar
  • 33 Wiggenhauser PS, Müller DF, Melchels FPW. et al. Engineering of vascularized adipose constructs. Cell Tissue Res 2012; 347: 747-757
    CrossrefPubMedGoogle Scholar
  • 34 Kral JG, Crandall DL. Development of a human adipocyte synthetic polymer scaffold. Plast. Reconstr. Surg 1999; 104: 1732-1738
    CrossrefPubMedGoogle Scholar
  • 35 Patel PN, Gobin AS, West JL. et al. Poly(ethylene glycol) hydrogel system supports preadipocyte viability, adhesion, and proliferation. Tissue Eng 2005; 11: 1498-1505
    CrossrefPubMedGoogle Scholar
  • 36 Stosich MS, Mao JJ. Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery. Plast. Reconstr. Surg 2007; 119: 71-83 discussion 84–5
    CrossrefPubMedGoogle Scholar
  • 37 Choi YC, Choi JS, Kim BS. et al. Decellularized Extracellular Matrix Derived from Porcine Adipose Tissue as a Xenogeneic Biomaterial for Tissue Engineering. Tissue engineering. Part C, Methods. 2012
    PubMedGoogle Scholar
  • 38 Flynn LE, Prestwich GD, Semple JL. et al. Proliferation and differentiation of adipose-derived stem cells on naturally derived scaffolds. Biomaterials 2008; 29: 1862-1871
    CrossrefPubMedGoogle Scholar
  • 39 Kawaguchi N, Toriyama K, Nicodemou-Lena E. et al. De novo adipogenesis in mice at the site of injection of basement membrane and basic fibroblast growth factor. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 1062-1066
    CrossrefPubMedGoogle Scholar
  • 40 Cronin KJ, Messina A, Knight KR. et al. New murine model of spontaneous autologous tissue engineering, combining an arteriovenous pedicle with matrix materials. Plast. Reconstr. Surg 2004; 113: 260-269
    CrossrefPubMedGoogle Scholar
  • 41 Ito R, Morimoto N, Liem PH. et al. Adipogenesis using human adipose tissue-derived stromal cells combined with a collagen/gelatin sponge sustaining release of basic fibroblast growth factor. J Tissue Eng Regen Med 2014; 8: 1000-1008
    CrossrefPubMedGoogle Scholar
  • 42 Torio-Padron N, Baerlecken N, Momeni A. et al. Engineering of adipose tissue by injection of human preadipocytes in fibrin. Aesthetic Plast Surg 2007; 31: 285-293
    CrossrefPubMedGoogle Scholar
  • 43 Sengupta D, Heilshorn SC. Protein-engineered biomaterials: highly tunable tissue engineering scaffolds. Tissue Eng Part B Rev 2010; 16: 285-293
    CrossrefPubMedGoogle Scholar
  • 44 Kang JH, Gimble JM, Kaplan DL. In vitro 3D model for human vascularized adipose tissue. Tissue Eng Part A 2009; 15: 2227-2236
    CrossrefPubMedGoogle Scholar
  • 45 Jing W, Lin Y, Wu L. et al. Ectopic adipogenesis of preconditioned adipose-derived stromal cells in an alginate system. Cell Tissue Res 2007; 330: 567-572
    CrossrefPubMedGoogle Scholar
  • 46 Hemmrich K, Heimburg D von, Rendchen R. et al. Implantation of preadipocyte-loaded hyaluronic acid-based scaffolds into nude mice to evaluate potential for soft tissue engineering. Biomaterials 2005; 26: 7025-7037
    CrossrefPubMedGoogle Scholar
  • 47 Baluk P, McDonald DM. Markers for microscopic imaging of lymphangiogenesis and angiogenesis. Ann. N. Y. Acad. Sci 2008; 1131: 1-12
    CrossrefPubMedGoogle Scholar
  • 48 Tanaka Y, Sung K, Tsutsumi A. et al. Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop or arteriovenous bundle, has more potential for angiogenesis and tissue generation?. Plast. Reconstr. Surg 2003; 112: 1636-1644
    CrossrefPubMedGoogle Scholar
  • 49 Dolderer JH, Kehrer A, Schiller SM. et al. De-novo Generierung von vaskularisiertem Gewebe mittels unterschiedlicher Gefäßstielkonfigurationen in perforierten und geschlossenen Wachstumskammern. Wien Med Wochenschr 2010; 160: 139-146
    CrossrefPubMedGoogle Scholar
  • 50 Dolderer JH, Abberton KM, Thompson EW. et al. Spontaneous large volume adipose tissue generation from a vascularized pedicled fat flap inside a chamber space. Tissue Eng 2007; 13: 673-681
    CrossrefPubMedGoogle Scholar
  • 51 Lokmic Z, Stillaert F, Morrison WA. et al. An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct. FASEB J 2007; 21: 511-522
    CrossrefPubMedGoogle Scholar
  • 52 Ingber DE, Tensegrity I. Cell structure and hierarchical systems biology. J. Cell. Sci 2003; 116: 1157-1173
    CrossrefPubMedGoogle Scholar
  • 53 Findlay MW, Dolderer JH, Trost N. et al. Tissue-engineered breast reconstruction: bridging the gap toward large-volume tissue engineering in humans. Plast. Reconstr. Surg 2011; 128: 1206-1215
    CrossrefPubMedGoogle Scholar
  • 54 Arkudas A.. et al. Combination of extrinsic and intrinsic pathways significantly accelerates axial vascularization of bioartificial tissues. Plast Reconstr Surg 2012; 129 (01) 55e-65e
    CrossrefPubMedGoogle Scholar
  • 55 Weigand A.. et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Engineering Part A 2015; 21 (09/10) 1680-1694
    CrossrefPubMedGoogle Scholar
  • 56 Dolderer JH, Thompson EW, Slavin P. et al. Long-term stability of adipose tissue generated from a vascularized pedicled fat flap inside a chamber. Plast. Reconstr. Surg 2011; 127: 2283-2292
    CrossrefPubMedGoogle Scholar