Biofabrication Strategies for Tissue Engineering

  • Paulo Jorge Bártolo
  • Marco Domingos
  • Tatiana Patrício
  • Stefania Cometa
  • Vladimir Mironov
Part of the Computational Methods in Applied Sciences book series (COMPUTMETHODS, volume 20)


The success of Tissue Engineering (TE) strongly relies on the capability of designing biomimetic scaffolds closely resembling the host tissue environment. Due to the functional multitude of the native tissues, the considerations are complex and include chemical, morphological, mechanical and biological factors and their mutability with time. Nonetheless, to trigger and/or assist the “natural healing mechanism’’ of the human body it seems essential to provide an appropriate biomechanical environment and biomolecular signalling to the cells. Novel biomanufacturing processes are increasingly being recognized as ideal techniques to produce 3D biodegradable structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. In this chapter, we discuss in detail the most recent advances in the field of biofabrication, providing and updated overview of processes and materials employed in the production of tissue engineering constructs. Bioprinting or ‘’scaffold-less’’ strategies are also presented in this work. They are based on the precise deposition of high-density tissue spheroids or cell aggregates being advantageous alternatives to the current scaffold-based tissue engineering approach.


Tissue Engineering Rapid Prototype Tissue Engineer Composite Scaffold Selective Laser Sinter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Schmitz JP, Hollinger JO (1988) A preliminary study of the osteogenic potential of a biodegradable alloplasticosteoinductive alloimplant, Clin Orthop Relat Res, 237, 245–551.Google Scholar
  2. 2.
    Whang K, Thomas CH, Healy KE and Nuber G (1995) A novel method to fabricate bioabsorbable scaffolds, Polymer, 36, 837–42.CrossRefGoogle Scholar
  3. 3.
    Hsu YY, Gresser JD, Trantolo DJ, Lyons CM, Gangadharam PR and Wise DL (1997) Effect of polymer foam morphology and density on kinetics of in vitro controlled release of isoniazid from compressed foam matrices, J Biomed Mater Res, 35, 107–116.CrossRefGoogle Scholar
  4. 4.
    Schoof H, Apel J, Heschel I and Rau G (2001) Control of pore structure and size in freeze-dried collagen sponges, J Biomed Mater Res, 58, 352–357.CrossRefGoogle Scholar
  5. 5.
    Lo HP and Leong KW (1995) Fabrication of controlled release biodegradable foams by phase separation Tissue Eng, 1, 15–28.Google Scholar
  6. 6.
    Mooney DJ, Baldwin DF, Suh NP, Vacanti JP and Langer R (1996) Novel approach to fabricate porous sponges of poly(D, L-lactic-co-glycolic acid) without the use of organic solvents, Biomaterials, 17, 1417–1422.CrossRefGoogle Scholar
  7. 7.
    Nazarov R, Jin HJ and Kaplan DL (2004) Porous 3D scaffolds from regenerated silk fibroin, Biomacromolecules, 5, 718–726.CrossRefGoogle Scholar
  8. 8.
    Thompson RC, Yaszemski MJ, Powers JM and Mikos AG (1995) Fabrication of biodegradable polymer scaffolds to engineering trabecular bone, J Biomater Sci-Polym, 7, 23–38.CrossRefGoogle Scholar
  9. 9.
    Cima LG, Vacanti JP, Vacanti C, Inger D, Mooney DJ and Langer R (1991) Tissue engineering by cell transplantation using degradable polymer substrates, J Biomech Eng, 113, 143–151.CrossRefGoogle Scholar
  10. 10.
    Hofmann S, Hagenmuller H, Koch AM, Muller R, Vunjak-Novakovic G, Kaplan DL, Merkle HP and Meinel L (2007) Control of in vitro tissue engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds, Biomaterials, 28, 1152–1162.CrossRefGoogle Scholar
  11. 11.
    Li WJ, Laurencin CT, Caterson EJ, Tuan RS and Ko FK (2002) Electrospun nanofibrous structure: a novel scaffold for tissue engineering, J Biomed Mater Res, 60, 613–621.CrossRefGoogle Scholar
  12. 12.
    Ma Z, Kotaki M, Inai R and Ramakrishna S (2005) Potential of nanofiber matrix as tissue-engineering scaffolds, Tissue Eng, 11, 101–109.CrossRefGoogle Scholar
  13. 13.
    Fedchenko F (1996) Stereolithography and other RP&M technologies, Edited by PF Jacobs, ASME Press.Google Scholar
  14. 14.
    Melchels FPW, Feijen J and Grijpma DW (2010) A review on stereolithography and its applications in biomedical engineering, Biomaterials, 31 (24), 6121–6130.CrossRefGoogle Scholar
  15. 15.
    Hutmacher DW, Cool S (2007) Concepts of scaffold-based tissue engineering - the rationale to use solid free-form fabrication techniques, J Cell Mol Med, 11, 654–669.CrossRefGoogle Scholar
  16. 16.
    Yeong W, Chua C, Leong K and Chandrasekaran M (2004) Rapid prototyping in tissue engineering: challenges and potential, Trend Biotechnol, 22, 643–652.CrossRefGoogle Scholar
  17. 17.
    Miot S, Woodfield T, Daniels AU, Suetterlin R, Peterschmitt I, Heberer M, van Blitterswijk CA, Riesle J and Martin I (2005) Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition, Biomaterials, 26, 2479–2489.CrossRefGoogle Scholar
  18. 18.
    Hutmacher DW, Kirsch A and Ackermann KL (2001) A tissue engineered cell-occlusive device for hard tissue regeneration—a preliminary report, Int J Periodontics Restorative Dent, 21, 49–59.Google Scholar
  19. 19.
    Hoque E, San WY, Wei F, Li S, Huang M-H, Vert M, Hutmacher DW (2009) Processing of polycaprolactone and polycaprolactone-based copolymers into 3D scaffolds, and their cellular responses, Tissue Engineering: Part A, 15 (10), 3013–3024.CrossRefGoogle Scholar
  20. 20.
    Landers R and Mulhaupt R (2000) Desktop manufacturing of complex objects, prototypes and biomedical scaffolds by means of computer-assisted design combined with computer-guided 3D plotting of polymers and reactive oligomers, Macromol Mater Eng, 282, 17–21.CrossRefGoogle Scholar
  21. 21.
    Landers R, Hubner U, Schmelzeisen R and Mülhaupt R (2002) Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for applications in tissue engineering, Biomaterials, 23, 4437–4447.CrossRefGoogle Scholar
  22. 22.
    Shen F, Cui YL, Yang LF, Yao KD, Dong XH, Jia WY and Shi HD (2000) A study on the fabrication of porous chitosan/gelatin network scaffold for tissue engineering, Polym Int, 49, 1596.CrossRefGoogle Scholar
  23. 23.
    Sherwood JK, Riley SL, Palazzolo R, Brown SC, Monkhouse DC, Coates M, Griffith LG, Landeen LK and Ratcliffe A (2002) A three-dimensional osteochondral composite scaffold for articular cartilage repair, Biomaterials, 23, 4739–4751.CrossRefGoogle Scholar
  24. 24.
    Mironov V, Boland T, Trusk T, Forgacs G and Markwald RR (2003) Organ printing: computer-aided jet-based 3D tissue engineering, Trends Biotechnol, 21, 157–161.CrossRefGoogle Scholar
  25. 25.
    Ringeisen BR, Othon CM, Barron JA, Young D and Spargo BJ (2006) Jet-based methods to print living cells. Biotechnol J, 1, 930–948.CrossRefGoogle Scholar
  26. 26.
    Boland T, Xu T, Damon B, Cui X (2006) Application of inkjet printing to tissue engineering, Biotechnol J,1, 910–917.CrossRefGoogle Scholar
  27. 27.
    Nakamura M, Kobayashi A, Takagi F, Watanabe A, Hiruma Y, Ohuchi K, Iwasaki Y, Horie M, Morita I and Takatani S (2006) Biocompatible inkjet printing technique for designed seeding of individual living cells, Tissue Eng, 11, 1658–1666.CrossRefGoogle Scholar
  28. 28.
    Saunders RE, Gough JE and Derby B (2008) Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing, Biomaterials, 29, 193–203.CrossRefGoogle Scholar
  29. 29.
    Chang R, Sun W (2009) Biofabrication of three-dimensional liver cell-embedded tissue constructs for in vitro drug metabolism model, LAP Lambert Academic Publishing.Google Scholar
  30. 30.
    Bártolo PJ, Almeida HA, Rezende RA, Laoui T and Bidanda B (2008) Advanced processes to fabricate scaffolds for tissue engineering, Virtual Prototyping & Bio-manufacturing in medical applications, Edited by PJ Bártolo and B Bidanda, Springer.Google Scholar
  31. 31.
    Holtorf HL, Jansen JA and Mikos AG (2006) Modulation of cell differentiation in bone tissue engineering constructs cultured in a bioreactor, Adv. Exp. Med. Biol., 585, 225–241.CrossRefGoogle Scholar
  32. 32.
    Bártolo PJ, Chua CK, Almeida HA, Chou SM and Lim ASC (2009) Biomanufacturing for tissue engineering: present and future trends, Virtual and Physical Prototyping, 4, 203–216.CrossRefGoogle Scholar
  33. 33.
    Samuel RE, Lee CR, Ghivizzani S, Evans CH, Yannas IV, Olsen BR and Spector M (2002) Delivery os plasmid DNA to articular chondrocytes via novel collagen-glycosaminoglycan matrices, Human Gene Therapy, 13, 791–802.CrossRefGoogle Scholar
  34. 34.
    Matsumoto T and Mooney DJ (2006) Cell instructive polymers, Adv Biochem Engin/Biotechnol, 102, 113–137.CrossRefGoogle Scholar
  35. 35.
    Sanz-Herrera JA, Garcia-Aznar JM and Doblaré M (2009) On scaffold designing for bone regeneration: a computational multiscale approach, Acta Biomaterialia, 5, 219–229.CrossRefGoogle Scholar
  36. 36.
    Hutmacher DW, Schantz JT, Lam CXF, Tan KC and Lim TC (2007) State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective, J Tissue Eng Regen Med, 1, 245–260.CrossRefGoogle Scholar
  37. 37.
    Anderson JM (1993) Mechanisms of inflammation and infection with implanted devices, Cardiovasc Pathol, 2, 33S–41S.CrossRefGoogle Scholar
  38. 38.
    Anderson JM (1988) Inflammatory response to implants, Trans Am Soc, Intern Organs, 24, 101–107.Google Scholar
  39. 39.
    Anderson JM (1998) Biocompatibility of tissue-engineered implants, Frontiers in Tissue Engineering, Edited by C.W. Patrick, A.G. Mikos, L.V. McIntire, Elsevier.Google Scholar
  40. 40.
    Hedberg EL, Shih CK, Lemoine JJ, Timmer MD, Liebschner MAK, Jansen JA and Mikos AG (2005) In vitro degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds, Biomaterials, 26, 3215–3225.CrossRefGoogle Scholar
  41. 41.
    Gilbert TW, Stewart-Akers AM and Badylak SF (2007) A quantitative method for evaluating the degradation of biologic scaffold materials, Biomaterials, 28, 147–150.CrossRefGoogle Scholar
  42. 42.
    Sung HJ, Meredith C, Johnson C and Galis ZS (2004) The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis, Biomaterials, 25, 5735–5742.CrossRefGoogle Scholar
  43. 43.
    Domingos M, Chiellini F, Cometa S, Giglio ED, Grillo-Fernandes E, Bártolo PJ and Chiellini E (2010) Evaluation of in vitro degradation of PCL scaffolds fabricated via BioExtrusion. Part 1: Influence of the degradation environment, Virtual and Physical Prototyping, 5, 1–9.Google Scholar
  44. 44.
    Leon y Leon CA (1998) New perspectives in mercury porosimetry, Adv. Colloid Interface Sci, 76/77, 341–72.Google Scholar
  45. 45.
    Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue M and Murata M (1998) BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis, J Biomed Mater Res, 39, 190–9.CrossRefGoogle Scholar
  46. 46.
    Story BJ, Wagner WR, Gaisser DM, Cook SD and Rust-Dawicki AM (1998) In vivo performance of a modified CSTi dental implant coating, Int J Oral Maxillofac Implants, 13, 749–57.Google Scholar
  47. 47.
    Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP and Langer R (1993) Prevascularization of porous biodegradable polymers, Biotechnol Bioeng, 42, 716–723.CrossRefGoogle Scholar
  48. 48.
    Rouwkema J, Rivron NC and van Blitterswijk CA (2008) Vascularization in tissue engineering, Trends in Biotechnology, 26, 434–441.CrossRefGoogle Scholar
  49. 49.
    Jones AC, Arns CH, Hutmacher DW, Milthorpe BK, Sheppard AP and Knackstedt MA (2009) The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth, Biomaterials, 30, 1440–1451.CrossRefGoogle Scholar
  50. 50.
    Hollister SJ, Maddox RD and Taboas JM (2002) Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints, Biomaterials, 23, 4095–4103.CrossRefGoogle Scholar
  51. 51.
    Lee J, Cuddihy MJ and Kotov NA (2008) Three-Dimensional Cell Culture Matrices: State of the Art, Tissue Engineering Part B, 14, 61–86.CrossRefGoogle Scholar
  52. 52.
    Leong KF, Chua CK, Sudarmadji N and Yeong WY (2008) Engineering functionally graded tissue engineering scaffolds, Journal of The Mechanical Behavior of Biomedical Materials, 1, 140–152.CrossRefGoogle Scholar
  53. 53.
    Oh SH, Park IK, Kim JM and Lee JH (2007) In vitro and in vivo characteristics of PCL scaffolds with pore size gradient fabricated by a centrifugation method, Biomaterials, 28, 1664–1671.CrossRefGoogle Scholar
  54. 54.
    Yang SF, Leong KF, Du ZH and Chua CK (2001) The design of scaffolds for use in tissue engineering. Part 1, traditional factors, Tissue Engineering, 7, 679–689.Google Scholar
  55. 55.
    Wang H, Pieper J, Péters F, Blitterswijk CA and Lamme EN (2005) Synthetic scaffold morphology controls human dermal connective tissue formation, Journal of Biomedical Materials Research Part A, 74, 523–532.CrossRefGoogle Scholar
  56. 56.
    Lawrence BJ and Madihally SV (2008) Cell colonization in 3D degradable porous matrices, Cell Adhesion & Migration, 2, 9–16.CrossRefGoogle Scholar
  57. 57.
    Shihong LI, Wijn JRD, Jiaping LI, Layrolle P and Groot KD (2003) Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio, Tissue Engineering, 9, 535–548.CrossRefGoogle Scholar
  58. 58.
    O’Brien FG, Harley BA, Waller MA, Yannas IV, Gibson LJ and Prendergast PJ (2007) The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering, Technology and Helth Care, 15, 3–17.Google Scholar
  59. 59.
    O’Brien FG, Harley BA, Yannas IV and Gibson LJ (2005) Effect of pore size on cell adhesion in collagen-gag scaffolds, Biomaterials, 26, 433–441.CrossRefGoogle Scholar
  60. 60.
    Stevens MM (2005) Exploring and engineering the cell surface interface, Science, 310, 1135–138.CrossRefGoogle Scholar
  61. 61.
    Price RL, Ellison K, Haberstroh KM and Webster TJ (2004) Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts, J Biomed Mater Res A, 70, 129–138.CrossRefGoogle Scholar
  62. 62.
    Curtis ASG, Gadegaard N, Dalby MJ, Riehle MO, Wilkinson CDW and Aitchison G (2004) Cells React to Nanoscale Order and Symmetry in Their Surroundings, IEEE Trans Nanobioscience, 3, 61–65.CrossRefGoogle Scholar
  63. 63.
    Boyan BD, Hummert TW, Dean DD and Schwartz Z (1996) Role of material surfaces in regulating bone and cartilage cell response, Biomaterials, 17, 137–146.CrossRefGoogle Scholar
  64. 64.
    McClary KB, Ugarova T and Grainger DW (2000) Modulating fibroblast adhesion, spreading, and proliferation using self-assembled monolayer films of alkylthiolates on gold, J Biomed Mater Res, 50, 428–439.CrossRefGoogle Scholar
  65. 65.
    Quirk RA, Chan WC, Davies MC, Tendler SJ and Shakesheff MK (2001) Poly(L-lysine)-GRGDS as a biomimetic surface modifier for poly(lactic acid), Biomaterials, 22, 865–872.CrossRefGoogle Scholar
  66. 66.
    Chu PK, Chen JY, Wang LP and Huang N (2002) Plasma-surface modification of biomaterials, Mater Sci Eng R, 36, 143–206.CrossRefGoogle Scholar
  67. 67.
    Yildirim ED, Besunder R, Pappas D, Allen F, Guceri S and Sun W (2010) Accelerated differentiation of osteoblast cells on polycaprolactone scaffolds driven by a combined effect of protein coating and plasma modification, Biofabrication, 2 (1).Google Scholar
  68. 68.
    Rejeb SB, Tatoulian M, Khonsari FA, Durand FA, Martel A, Lawrence JF (1998) Functionalization of nitrocellulose membranes using ammonia plasma for the covalent attachment of antibodies for use in membrane-based immunoassays, Anal Chim Acta, 376, 133–138.CrossRefGoogle Scholar
  69. 69.
    Puleo DA, Kissling RA and Sheu MS (2002) A technique to immobilize bioactive proteins, including bone morphogenetic protein-4 (BMP-4), on titanium alloy, Biomaterials, 23, 2079–2087.CrossRefGoogle Scholar
  70. 70.
    Daw R, O'Leary T, Kelly J, Short RD, Cambray-Deakin M, Devlin AJ, Brook IM, Scutt A and Kothari S (1999) Molecular Engineering of Surfaces by Plasma Copolymerization and Enhanced Cell Attachment and Spreading, Plasmas and Polymers, 4, 113–132.CrossRefGoogle Scholar
  71. 71.
    Hsiue GH, Lee SD, Wang CC, Shiue MHI and Chang PCT (1993) ppHEMA-modified silicone rubber film towards improving rabbit corneal epithelial cell attachment and growth, Biomaterials, 14, 591–597.CrossRefGoogle Scholar
  72. 72.
    Sipheia R, Martucci G, Barbarosie M and Wu C (1993) Enhanced Attachment and Growth of Human Endothelial Cells Derived from Umbilical Veins on Ammonia Plasma Modified Surfaces of Ptfe and EPTFE Synthetic Vascular Graft Biomaterials, Biomater, Artif Cell Im, 21 (4), 455.Google Scholar
  73. 73.
    Siow KS, Brichter L, Kumar S and Griesser HJ (2006) Plasma Methods for the Generation of Chemically Reactive Surfaces for Biomolecule Immobilization and Cell Colonization, Plasma Process Polym, 3, 392–418.CrossRefGoogle Scholar
  74. 74.
    Griesser HJ, Chatelier RC, Gengenbach TR, Johnson G and Steele JG (1994) Growth of human cells on plasma polymers: Putative role of amine and amide groups, J Biomater Sci Polym, 5, 531–554.CrossRefGoogle Scholar
  75. 75.
    Lopez LC, Gristina R, Ceccone G, Rossi F, Favia P and d’Agostino R (2005) Immobilization of RGD peptides on stable plasma-deposited acrylic acid coatings for biomedical devices, Surf Coat Technol, 200, 1000–1004.CrossRefGoogle Scholar
  76. 76.
    De Bartolo L, Morelli S, Lopez LC, Giorno L, Campana C, Salerno S, Rende M, Favia P, Detomaso L, Gristina R, d’Agostino R and Drioli E (2005) Biotransformation and liver-specific functions of human hepatocytes in culture on RGD-immobilized plasma-processed membranes, Biomaterials, 26, 4432–4441.Google Scholar
  77. 77.
    Sokolsky-Papkov M, Agashi K, Olaye A, Shakesheff K and Domb AJ (2007) Polymer carriers for drug delivery in tissue engineering, Advanced Drug Delivery Reviews, 59, 187–206.CrossRefGoogle Scholar
  78. 78.
    Lode A, Wolf-Brandstetter C, Reinstorf A, Bernhardt A, Konig U, Pompe W, Gelinsky M (2007) Calcium phosphate bone cements, functionalized with VEGF: Release kinetics and biological activity, J Biomed Mater Res A, 81, 474–483.Google Scholar
  79. 79.
    Murphy WL, Peters MC, Kohn DH and Mooney DJ (2000) Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering, Biomaterials, 21, 2521–2527.CrossRefGoogle Scholar
  80. 80.
    Kanczler JM, Barry J, Ginty P, Howdle SM, Shakesheff KM, Oreffo ROC (2007) Supercritical carbon dioxide generated vascular endothelial growth factor encapsulated poly(DL-lactic acid) scaffods induce angiogenesis in vitro, Biochem Biophys Res Commun, 352, 135–141.CrossRefGoogle Scholar
  81. 81.
    Gu F (2004) Sustained delivery of vascular endothelial growth factor with alginate beads, J Control Release, 96, 463–472.CrossRefGoogle Scholar
  82. 82.
    Arm DM, Tencer AF, Bain SD and Celino D (1996) Effect of controlled release of platelet-derived growth factor from a porous hydroxyapatite implant on bone ingrowth, Biomaterials, 17, 703–709.CrossRefGoogle Scholar
  83. 83.
    Delgado JJ, Evora C, Sanchez E, Baro M and Delgado A (2006) Validation of a method for non-invasive in vivo measurement of growth factor release from a local delivery system in bone, J Control Release, 114, 223–229.CrossRefGoogle Scholar
  84. 84.
    Nakahara T, Nakamura T, Kobayashi E, Inoue M, Shigeno K, Tabata Y, Eto K and Shimizu Y (2003) Novel approach to regeneration of periodontal tissues based on in situ tissue engineering: effects of controlled release of basic fibroblast growth factor from a sandwich membrane, Tissue Engineering, 9, 153–162.CrossRefGoogle Scholar
  85. 85.
    Wei GB, Jin QM, Giannobile WV and Ma PX (2006) Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB, J Control Release, 112, 103–110.CrossRefGoogle Scholar
  86. 86.
    Mogi M, Kondo A, Kinpara K and Togari A (2000) Antiapoptotic action of nerve growth factor in mouse osteoblastic cell line, Life Sci, 67, 1197–1206.CrossRefGoogle Scholar
  87. 87.
    Letic-Gavrilovic A, Piattelli A and Abe K (2003) Nerve growth factor beta(NGF beta) delivery via a collagen/hydroxyapatite (Col/HAp) composite and its effects on new bone ingrowth, J Mater Sci Mater Med, 14, 95–102.CrossRefGoogle Scholar
  88. 88.
    Begley DJ (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities, Pharmacol Ther, 104, 29–45.CrossRefGoogle Scholar
  89. 89.
    Premaraj S, Mundy B, Parker-Barnes J, Winnard PL and Moursi AM (2005) Collagen gel delivery of Tgfbeta3 non-viral plasmid DNA in rat osteoblast and calvarial culture, Orthod Craniofac Res, 8, 320–322.CrossRefGoogle Scholar
  90. 90.
    Gombotz WR, Pankey SC, Bouchard LS, Ranchalis J and Puolakkainen P (1993) Controlled release of TGF-beta 1 from a biodegradable matrix for bone regeneration, J Biomater Sci Polym, 5, 49–63.CrossRefGoogle Scholar
  91. 91.
    Jaklenec A, Hinckfuss A, Bilgen B, Ciombor DM, Aaron R and Mathiowitz E (2008) Sequential release of bioactive IGF-I and TGF-b1 from PLGA microsphere-based scaffolds, Biomaterials, 29, 1518–1525.CrossRefGoogle Scholar
  92. 92.
    Park H, Temenoff JS, Holland TA, Tabata Y and Mikos AG (2005) Delivery of TGF b1 and chondrocytes via injectable, biodegradable hydrogels for cartilage tissue engineering applications, Biomaterials, 26, 7095–7103.CrossRefGoogle Scholar
  93. 93.
    Li C, Vepari C, Jin HJ, Kim HJ and Kaplan DL (2006) Electrospun silk-BMP-2 scaffolds for bone tissue engineering, Biomaterials, 27, 3115–3124.CrossRefGoogle Scholar
  94. 94.
    Yilgor P, Tuzlakoglu K, Reis RL, Hasirci N and Hasirci V (2009) Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering, Biomaterials, 30, 3551–3559.CrossRefGoogle Scholar
  95. 95.
    Chen B, Lin H, Wang J, Zhao Y, Wang B, Zhao W, Sun W and Dai J (2007) Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2, Biomaterials, 28, 1027–1035.CrossRefGoogle Scholar
  96. 96.
    Rai B, Teoh SH, Ho KH, Hutmacher DW, Cao T, Chen F, Yacob K (2004) The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive polycaprolactone scaffolds, Biomaterials, 25, 5499–5506.CrossRefGoogle Scholar
  97. 97.
    Shen H, Hu X, Bei J and Wang S (2008) The immobilization of basic fibroblast growth factor on plasmatreated poly(lactide-co-glycolide), Biomaterials, 29, 2388–2399.CrossRefGoogle Scholar
  98. 98.
    Delong SA, Moon JJ and West JL (2005) Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration, Biomaterials, 26, 3227–3234.CrossRefGoogle Scholar
  99. 99.
    Leong KF, Cheah CM and Chua CK (2003) Solid freeform fabrication of the three-dimensional scaffolds for engineering replacement tissues and organs, Biomaterials, 24, 2363–2378.CrossRefGoogle Scholar
  100. 100.
    Bártolo PJ, Almeida HA and Laoui T (2009) Rapid prototyping and manufacturing for tissue engineering scaffolds, Int J Computer Applications in Technology, 36, 1–9.CrossRefGoogle Scholar
  101. 101.
    Wiria FE, Chua CK, Leong KF, Quah ZY, Chandrasekaran M, Lee MW (2008) Improved biocomposite development of poly(vinyl alcohol) and hydroxyapatite for tissue engineering scaffold fabrication using selective laser sintering, J Mater Sci: Mater Med, 19, 989–996.CrossRefGoogle Scholar
  102. 102.
    Nair LS and Laurencin CT (2006) Polymers as biomaterials for tissue engineering and controlled drug delivery, Adv Biochem Engin/Biotechnol, 102, 47–90.CrossRefGoogle Scholar
  103. 103.
    Velema J and Kaplan D (2006) Biopolymer-based biomaterials as scaffolds for tissue engineering, Adv Biochem Engin/Biotechnol, 102, 187–238.CrossRefGoogle Scholar
  104. 104.
    Chan G and Mooney DJ (2008) New materials for tissue engineering: towards greater control over the biological response, Trends in Biotechnology, 26, 382–392.CrossRefGoogle Scholar
  105. 105.
    Bártolo PJ (2001) Optical approaches to macroscopic and microscopic engineering, PhD Thesis, University of Reading, UK.Google Scholar
  106. 106.
    Bártolo PJ, Mendes A and Jardini A (2004) Bio-prototyping, Design and Nature II – Comparing design in nature with science and engineering, Edited by CA Brebbia, L Sucharov, P Pascolo, WIT Press.Google Scholar
  107. 107.
    Ritman EL (2004) Micro-computed tomography – Current status and developments, Annual Review of Biomedical Engineering, 6, 185–208.CrossRefGoogle Scholar
  108. 108.
    Potter HG, Nestor BJ, Sofka CM, Ho ST, Peters LE, Salvati EA (2004) Magnetic Resonance Imaging After Total Hip Arthroplasty: Evaluation of Periprosthetic Soft Tissue, The Journal of Bone and Joint Surgery, 86, 1947–1954.Google Scholar
  109. 109.
    Fenster A, Downey DB (2002) 3-D ultrasound imaging: a review, Engineering in Medicine and Biology Magazine, 15 (6), 41–51.Google Scholar
  110. 110.
    McElroy DP, MacDonald LR, Beekman FJ, Yuchuan W, Patt BE, Iwanczyk JS, Tsui BMW, and Hoffman EJ (2002) Performance evaluation of A-SPECT: a high resolution desktop pinhole SPECT system for imaging small animals, Nuclear Science, 49 (5), 2139–2147.CrossRefGoogle Scholar
  111. 111.
    Edinger M, Cao Y, Hornig YS, Jenkins DE, Verneris MR, Bachmann MH, Negrin RS, Contag CH (2002) Advancing animal models of neoplasia through in vivo bioluminescence imaging, European Journal of Cancer, 38 (16), 2128–2136.CrossRefGoogle Scholar
  112. 112.
    Chua CK, Leong KF and Lim CS (2003) Rapid prototyping: principles and applications, World Science Publishing, Singapore.Google Scholar
  113. 113.
    Alves NM and Bártolo PJ (2006) Integrated computational tools for virtual and physical automatic construction, Automation in Construction, 15, 257–271.CrossRefGoogle Scholar
  114. 114.
    Szilvási-Nagy M and Mátyási G (2003) Analysis of STL files, Mathematical and Computer Modelling 38, 945–960.MathSciNetzbMATHCrossRefGoogle Scholar
  115. 115.
    Zhang LC, Han M and Huang SH (2003) CS file – an improvement interface between CAD and rapid prototyping systems, Int J Adv Manuf Technol, 21, 15–19.CrossRefGoogle Scholar
  116. 116.
    Chen YH (1999) Y Z Data reduction in integrated reverse engineering and rapid prototyping, Int Journal of Computer Integrated Manufacturing, 12, 97–103.CrossRefGoogle Scholar
  117. 117.
    MK Agoston (1976) Algebraic Topology, Marcel Dekker, New York.zbMATHGoogle Scholar
  118. 118.
    Jackson TR, Liu H, Patrikalakis NM (1999) EM Sachs and MJ Cima, Modeling and designing functionally graded material components for fabrication with local composition control, Materials in Design, 20, 63–75.Google Scholar
  119. 119.
    Zhou MY, Xi JT and Yan JQ (2004) Modeling and processing of functionally graded materials for rapid prototyping, Journal of Materials Processing Technology, 146, 396–402.CrossRefGoogle Scholar
  120. 120.
    Wu XJ, Liu WJ and Wang MY (2007) Modeling heterogeneous objects in CAD, Computer-Aided Design & Applications, 4, 731–740.Google Scholar
  121. 121.
    Cai S and Xi J (2009) Morphology-controllable modeling approach for porous scaffold structure in tissue engineering, Virtual and Physical Prototyping, 4, 149–163.CrossRefGoogle Scholar
  122. 122.
    He J, Li D, Liu Y, Gong H, Lu B (2008) Indirect fabrication of microstructured chitosan-gelatin scaffolds using rapid prototyping, Virtual and Physical Prototyping, 3, 159–166.CrossRefGoogle Scholar
  123. 123.
    Bártolo PJ (2006) State of the art of solid freeform fabrication for soft and hard tissue engineering, Design and Nature III: Comparing Design in Nature with Science and Engineering, WIT Press, UK.Google Scholar
  124. 124.
    Bártolo PJ and Mitchell G (2003) Stereo-thermal-lithography, Rapid Prototyping Journal, 9,150–156.CrossRefGoogle Scholar
  125. 125.
    Deshmukh S and Gandhi PS (2009) Optomechanical scanning system for microstereolithography (MSL): analysis and experimental verification, Journal of Materials Processing Technology, 209, 1275–1285.CrossRefGoogle Scholar
  126. 126.
    Kang H-W, Seol Y-J, Cho D-W (2009) Development of an indirect solid freeform fabrication process based on microstereolithography for 3D porous scaffolds, J Micromech Microeng, 19 (1), doi: 10.1088/0960-1317/19/1/015011.Google Scholar
  127. 127.
    Levy RA, Chu TG, Holloran JW (1997) SE Feinberg and S Hollister, CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant, American Journal of Neuroradiology, 18, 1522–1525.Google Scholar
  128. 128.
    Griffith ML and Halloran JW (1996) Freeform fabrication of ceramics via stereolithography, Journal of the American Ceramic Society, 79, 2601–2608.CrossRefGoogle Scholar
  129. 129.
    Chu TG, Halloran JW, Hollister SJ, and Feinberg SE (2001) Hydroxyapatite implants with designed internal architecture, Journal of Materials Science: Materials in Medicine, 12, 471–478.CrossRefGoogle Scholar
  130. 130.
    Cooke MN, Fisher JP, Dean D, Rimnac C and Mikos AG (2002) Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 64B, 65–69.Google Scholar
  131. 131.
    Lan PX, Lee JW, Seol YJ, Cho DW (2009) Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification, J Mater Sci: Mater Med, 20, 271–279.CrossRefGoogle Scholar
  132. 132.
    Melchels FP, Feijen J and Grijpma DW (2009) A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography, Biomaterials, 30, 3801–3809.CrossRefGoogle Scholar
  133. 133.
    Liu VA and Bhatia SN (2002) Three-dimensional patterning of hydrogels containing living cells, Biomed Microdevices, 4, 257–266.CrossRefGoogle Scholar
  134. 134.
    Bartolo PJ (2008) Multimaterial microstereo-termo-litografia (microSTLG), Research project financed by the Portuguese Foundation for Science and Technology (FCT).Google Scholar
  135. 135.
    Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, Hollister SJ and Das S (2005) Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering, Biomaterials, 26, 4817–4827.CrossRefGoogle Scholar
  136. 136.
    Lee G and Barlow JW (1996) Selective laser sintering of bioceramic materials for implants, Proceedings of the ‘96 SFF Symposium, Austin.Google Scholar
  137. 137.
    Zhou WY, Lee SH, Wang M, Cheung WL and Ip WY (2008)Selective laser sintering of porous tissue engineering scaffolds from poly(L-lactide)/carbonated hydroxyapatite nanocomposite microspheres, J Mater Sci:Mater Med, 19, 2535–2540.CrossRefGoogle Scholar
  138. 138.
    Hao L, Savalani MM, Zhang Y, Tanner KE, Harris RA (2006) Selective Laser Sintering of Hydroxyapatite Reinforced Polyethylene Composites for Bioactive Implants and Tissue Scaffold Development, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 220 (4), 521–531.CrossRefGoogle Scholar
  139. 139.
    Naing MW, Chua CK and Leong KF (2008) Computer aided tissue engineering scaffold fabrication, Virtual Prototyping & Biomanufacturing in Medical Applications, Edited by B Bidanda and PJ Bártolo, Springer.Google Scholar
  140. 140.
    Tan KH, Chua CK, Leong KF, Cheah CM, Cheang P, Abu Bakar MS and Cha SW (2003) Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends, Biomaterials, 24, 3115–3123.CrossRefGoogle Scholar
  141. 141.
    Crump SS (1989) Apparatus method for creating three-dimensional objects, US Pat. 5121329.Google Scholar
  142. 142.
    Hutmacher DW, Schantz T, Zein I, Ng KW, Teoh SH and Tan KC (2001)Mechanical properties and cell culture response of polycaprolactone scaffolds designed and fabricated via fused deposition modelling, Journal of Biomedical Materials Research, 55, 203–216.CrossRefGoogle Scholar
  143. 143.
    Zein I, Hutmacher DW, Tan KC and Teoh SH (2002) Fused deposition modelling of novel scaffold architectures for tissue engineering applications, Biomaterials, 23, 1169–1185.CrossRefGoogle Scholar
  144. 144.
    Woodfield TB, Malda J, de Wijn J, Péters F, Riesle J and van Blitterswijk CA (2004) Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique, Biomaterials, 25, 4149–4161.CrossRefGoogle Scholar
  145. 145.
    Wang F, Shor L, Darling A, Khalil S, Güçeri S and Lau A (2004) Precision deposition and characterization of cellular poly-ε-caprolactone tissue scaffolds, Rapid Prototyping Journal, 10, 42–49.CrossRefGoogle Scholar
  146. 146.
    Yildirim ED, Besunder R, Guceri S, Allen F and Sun W (2008) Fabrication and plasma treatment of 3D polycaprolactone tissue scaffolds for enhanced cellular function, Virtual and Physical Prototyping, 3, 199–207.CrossRefGoogle Scholar
  147. 147.
    Park S, Kim G, Jeon YC, Koh Y and Kim W (2009) 3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system, J Mater Sci: Mater Med, 20, 229–234.CrossRefGoogle Scholar
  148. 148.
    Rath SN, Cohn D and Hutmacher DW (2008) Comparison of chondrogenesis in static and dynamic environments using a SFF designed and fabricated PCL-PEO scaffold, Virtual and Physical Prototyping, 3, 209–219.CrossRefGoogle Scholar
  149. 149.
    Xiong Z, Yan Y, Zhang R and Wang X (2005) Organism manufacturing engineering based on rapid prototyping principles, Rapid Prototyping Journal, 11, 160–166.CrossRefGoogle Scholar
  150. 150.
    Vozzi G, Flaim C, Ahluwalia A and Bhatia S (2003) Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition, Biomaterials, 24, 2533–2540.CrossRefGoogle Scholar
  151. 151.
    Miranda P, Saiz E, Gryn K and Tomsia AP (2006) Sintering and robocasting of β-tricalcium phosphate scaffolds for orthopaedic applications, Acta Biomaterialia, 2, 457–466.CrossRefGoogle Scholar
  152. 152.
    Miranda P, Pajares A, Saiz E, Tomsia AP and Guiberteau F (2008) Mechanical properties of calcium phosphate scaffolds fabricated by robocasting, J Biomed Mater Res A, 85 (1), 218 227.Google Scholar
  153. 153.
    Yan Y, Zhang R and Lin F (2003) Research and applications on bio-manufacturing, Proceedings of the 1st International Conference on Advanced Research in Virtual and Rapid Prototyping, School of Technology and Management, Leiria, Portugal.Google Scholar
  154. 154.
    C Mota, A Mateus, PJ Bártolo, H Almeida and N Ferreira, Processo e equipamento de fabrico rápido por bioextrusão/Process and equipment for rapid fabrication through bioextrusion’, Portuguese Patent nº104247, 2010Google Scholar
  155. 155.
    Domingos M, Dinucci D, Cometa S, Alderighi M, Bártolo PJ and Chiellini F (2009) Polycaprolactone scaffolds fabricated via bioextrusion for tissue engineering applications, International Journal of Biomaterials, 2009, 1–9.CrossRefGoogle Scholar
  156. 156.
    Domingos M, Chiellini F, Gloria A, Ambrosio L, Bártolo PJ and Chiellini E (2010) Bioextruder: study of the influence of process parameters on PCL scaffolds properties, Innovative Developments in Design and Manufacturing, Edited by PJ Bártolo et al, CRC Press.Google Scholar
  157. 157.
    Sachs EM, Haggerty JS, Cima MS, Williams PA (1989) Three-dimensional printing techniques, US Pat. 5204055.Google Scholar
  158. 158.
    Kim SS, Utsunomiya H, Koski JA, Wu BM, Cima MJ, Sohn J, Mukai K, Griffith LG and Vacanti JP (1998) Survival and function of hepatocytes o a novel three-dimensional synthetic biodegradable polymer scaffolds with an intrinsic network of channels, Annals of Surgery, 228, 8–13.CrossRefGoogle Scholar
  159. 159.
    Lam CX, Mo XM, Teoh SH and Hutmacher DW (2002) Scaffold development using 3D printing with a starch-based polymer, Materials Science and Engineering, 20, 49–56.CrossRefGoogle Scholar
  160. 160.
    Leukers B, Gülkan H, Irsen SH, Milz S, Tille C, Schieker M and Seitz H (2005) Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing, Journal of Materials Science: Materials in Medicine, 16 (12), 1121–1124.CrossRefGoogle Scholar
  161. 161.
    Cui X, Human microvasculature fabrication using thermal inkjet printing technology, Biomaterials, 30, 6221–6227, 2009CrossRefGoogle Scholar
  162. 162.
    Sachlos E, Reis N, Ainsley C, Derby B and Czernuszka JT ( 2003) Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication, Biomaterials, 24 (8), 1487–1497.CrossRefGoogle Scholar
  163. 163.
    Lee M, Dunn JC, Wu BM (2005) Scaffold fabrication by indirect three-dimensional printing, Biomaterials, 26 (20), 4281–4289.CrossRefGoogle Scholar
  164. 164.
    Mironov V (2009) Biofabrication: a 21st Century Manufacturing Paradigm, Biofabrication, 1.Google Scholar
  165. 165.
    Williams D (2009) On the nature of biomaterials, Biomaterials, 30 (30), 5897–5909, 2009Google Scholar
  166. 166.
    Mironov V (2009) Organ printing: tissue spheroids as building blocks, Biomaterials, 30 (12), 2164–2174, 2009Google Scholar
  167. 167.
    Chisti Y (2008) Biodiesel from microalgae beats bioethanol, Trends Biotechnol, 26 (3), 126–131, 2008.Google Scholar
  168. 168.
    Keriquel V (2010) In vivo bioprinting for computer- and robotic-assisted medical intervention: preliminary study in mice, Biofabrication, 2 (1), 2010.CrossRefGoogle Scholar
  169. 169.
    Cohen DL (2006) Direct freeform fabrication of seeded hydrogels in arbitrary geometries, Tissue Eng, 12 (5), 1325–1335.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media 2011

Authors and Affiliations

  • Paulo Jorge Bártolo
    • 1
  • Marco Domingos
    • 1
  • Tatiana Patrício
    • 1
  • Stefania Cometa
    • 2
  • Vladimir Mironov
    • 3
  1. 1.Centre for Rapid and Sustainable Product DevelopmentPolytechnic Institute of Leiria, Centro Empresarial da Marinha GrandeMarinha GrandePortugal
  2. 2.Department of Chemistry & Industrial ChemistryUniversity of PisaPisaItaly
  3. 3.Advanced Tissue Biofabrication Center, Department of Regenerative Medicine and Cell BiologyMedical University of South Carolina CharlestonCharlestonUSA

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