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Additive Manufacturing

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  • Progress in Polymer Science 37 (2012) 1079 1104

    Contents lists available at SciVerse ScienceDirect

    Progress in Polymer Science

    j ourna l ho me pag e: ww w.elsev ier .com/ locate /ppolysc i

    Additive manufacturing of tissues and organs

    Ferry P.W. Melchelsa,b,1, Marco A.N. Domingosc,2, Travis J. Kleina,3,Jos Maldaa,b,4, Paulo J. Bartoloc,5, Dietmar W. Hutmachera,d,

    a Institute of Hb Department oc Centre for RaGrande, Portugd George W Wo

    a r t i c l

    Article history:Received 12 MReceived in re15 November Accepted 17 November 2011Available online 8 December 2011

    Keywords:Additive manuBioprintingBiofabricationHydrogelsTissue enginee

    in combination with different biomaterials can be generated. The level of control offered bythese computer-controlled technologies to design and fabricate tissues will accelerate ourunderstanding of the governing factors of tissue formation and function. Moreover, it willprovide a valuable tool to study the effect of anatomy on graft performance. In this review,

    Contents

    1. The ra2. Histor3. State-

    3.1. 3.2. 3.3.

    Correspon60 Musk Aven

    E-mail [email protected]

    1 Tel.: +61 72 Tel.: +3513 Tel.: +61 74 Tel.: +31 85 Tel.: +351

    0079-6700/$ doi:10.1016/j.facturing

    ring

    we discuss the rationale for engineering tissues and organs by combining computer-aideddesign with additive manufacturing technologies that encompass the simultaneous depo-sition of cells and materials. Current strategies are presented, particularly with respect tolimitations due to the lack of suitable polymers, and requirements to move the currentconcepts to practical application.

    2011 Elsevier Ltd. All rights reserved.

    tionale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1080ical overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1081of-the-art . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10832D patterning and direct cell manipulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1083Additive manufacturing techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1084Biomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10863.3.1. Scaffold materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10863.3.2. Hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10873.3.3. Scaffold-free tissue manufacture approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1088

    ding author at: Queensland University of Technology, Institute of Health and Biomedical Innovation, Chair Regenerative Medicine,ue, Kelvin Grove, QLD 4059, Australia. Tel.: +61 7 3138 6077; fax: +61 7 3138 6030.resses: [email protected] (F.P.W. Melchels), [email protected] (M.A.N. Domingos), [email protected] (T.J. Klein),utrecht.nl (J. Malda), [email protected] (P.J. Bartolo), [email protected] (D.W. Hutmacher).

    3138 0503; fax: +61 7 3138 6030. 244 569 441; fax: +351 244 569 444.

    3138 6142; fax: +61 7 3138 6030.8 755 8078; fax: +31 30 2510638.

    244 569 441; fax: +351 244 569 444.

    see front matter 2011 Elsevier Ltd. All rights reserved.progpolymsci.2011.11.007ealth and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australiaf Orthopaedics, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlandspid and Sustainable Product Development (CDRsp), Polytechnic Institute of Leiria, Rua de Portugal Zona Industrial, 2430-028 Marinhaalodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    e i n f o

    ay 2011vised form2011

    a b s t r a c t

    Additive manufacturing techniques offer the potential to fabricate organized tissue con-structs to repair or replace damaged or diseased human tissues and organs. Using thesetechniques, spatial variations of cells along multiple axes with high geometric complexity

  • 1080 F.P.W. Melchels et al. / Progress in Polymer Science 37 (2012) 1079 1104

    4. Challenges and current developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10894.1. Construct design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10894.2. Hardware . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10904.3. Biomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1093

    4.3.1. Degradation properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    4.4. . . . . . . . 4.5. . . . . . . . 4.6. . . . . . . . .

    5. Futur . . . . . . . .5.1. . . . . . . . .5.2. . . . . . . . 5.3. . . . . . . . . 5.4. or testi5.5. . . . . . . .

    6. Concl . . . . . . . Ackno . . . . . . . Refer

    Nomenc

    2PP AM BLP CAD CT DA DMD ECM FDM HA HEMA LCST MA MMP NIPAAmPEG PPO RP SFF SLA SLS SPECT STL TEC

    1. The rati

    The funing is to coand/or biolneering coregeneratioport structuor matrix (olated) is exthe suppordifferentiat4.3.2. Mechanical properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4.3.3. Hybrid structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Scale-up of the AM process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Regulatory and commercialization aspects . . . . . . . . . . . . . . . . . . . . . .

    e directions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Modular tissue assembly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Convergence of techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Automation of pre- and post-manufacturing phases . . . . . . . . . . . . Manufacturing of tissue-like constructs for drug discovery and/In situ additive manufacturing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    usion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .wledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    lature

    two-photon polymerizationadditive manufacturingbiolaserprintingcomputer-aided designcomputed tomographydiacrylatedigital mirror deviceextracellular matrixfused deposition modelinghyaluronic acidhydroxyethyl methacrylatelower critical solution temperaturemethacrylatematrix metalloproteinases

    N-isopropylacrylamidepoly(ethylene glycol)poly(propylene oxide)rapid pro