MSA  Vol.7 No.8 , August 2016
3D Printed Scaffolds as a New Perspective for Bone Tissue Regeneration: Literature Review
Abstract: Due to the high incidence of bone fractures in the population, it became necessary to produce scaffolds that are able to assist in tissue regeneration. It is necessary to find an appropriate balance between the mechanical and biological properties, in order to mimic the natural tissue, these properties are directly related to the architecture and their degree of porosity, as well as the size of their pores and their interconnectivity. In this perspective, the 3D printing stands out, where the structure is obtained layer by layer, according to a predetermined computational model which provides a greater control of architecture and scaffold geometry and overcomes, in this way, the limitations of traditional techniques of scaffolds manufacturing. In this way, the objective of this seminar is to present the state of the art of the polymer scaffolds produced by 3D printing and applied to bone tissue regeneration, highlighting the advantages and limitations of this process.
Cite this paper: de Azevedo Gonçalves Mota, R. , da Silva, E. , de Lima, F. , de Menezes, L. and Thiele, A. (2016) 3D Printed Scaffolds as a New Perspective for Bone Tissue Regeneration: Literature Review. Materials Sciences and Applications, 7, 430-452. doi: 10.4236/msa.2016.78039.

[1]   Mano, J.F., Sousa, R.A., Boesel, L.F., Neves, N.M. and Reis, R.L. (2004) Bioinert, Biodegradable and Inject Able Polymeric Matrix Composites for Hard Tissue Replacement: State of the Art and Recent Developments. Composites Science and Technology, 64, 789-817.

[2]   Patrício, T., Domingos, M., Gloria, A. and Bártolo, P. (2013) Characterisation of PCL and PCL/PLA Scaffolds for Tissue Engineering. Procedia CIRP, 5, 110-114.

[3]   Melchels, F.P.W., Domingos, M.A.N., Klein, T.J., Malda, J., Bartolo, P.J. and Hutmacher, D.W. (2012) Additive Manufacturing of Tissues and Organs. Progress in Polymer Science, 37, 1079-1104.

[4]   Patterson, J., Martino, M.M. and Hubbell, J.A. (2010) Biomimetic Materials in Tissue Engineering. Materials Today, 13, 14-22.

[5]   Huang, R., Zhu, X., Tu, H. and Wan, A. (2014) The Crystallization Behavior of Porous Poly(Lactic Acid) Prepared by Modified Solvent Casting/Particulate Leaching Technique for Potential Use of Tissue Engineering Scaffold. Materials Letters, 136, 126-129.

[6]   Sin, D., Miao, X., Liu, G., Wei, F., Chadwick, G., Yan, C., et al. (2010) Polyurethane (PU) Scaffolds Prepared by Solvent Casting/Particulate Leaching (SCPL) Combined with Centrifugation. Materials Science and Engineering: C, 30, 78-85.

[7]   Mozafari, M., Moztarzadeh, F., Rabiee, M., Azami, M., Maleknia, S., Tahriri, M., et al. (2010) Development of Macroporous Nanocomposite Scaffolds of Gelatin/Bioactive Glass Prepared through Layer Solvent Casting Combined with Lamination Technique for Bone Tissue Engineering. Ceramics International, 36, 2431-2439.

[8]   Nam, Y.S., Yoon, J.J. and Park, T.G. (1999) A Novel Fabrication Method of Macroporous Biodegradable Polymer Scaffolds Using Gas Foaming Salt as a Porogen Additive. Journal of Biomedical Materials Research Part A, 53, 1-7.<1::AID-JBM1>3.0.CO;2-R

[9]   Salerno, A., Fernández-Gutiérrez, M., del Barrio, J.S.R. and Domingo, C. (2015) Bio-Safe Fabrication of PLA Scaffolds for Bone Tissue Engineering by Combining Phase Separation, Porogen Leaching and scCO2 Drying. The Journal of Supercritical Fluids, 97, 238-246.

[10]   Zhu, X.H., Lee, L.Y., Sheng, J., Jackson, H., Tong, Y.W. and Wang, C. (2008) Characterization of Porous Poly(D, L-Lactic-co-Glycolic Acid) Sponges Fabricated by Supercritical CO2 Gas-Foaming Method as a Scaffold for Three-Dimensional Growth of Hep3B Cells. Biotechnology and Bioengineering, 100, 998-1009.

[11]   Nam, Y.S. and Park, T.G. (1999) Porous Biodegradable Polymeric Scaffolds Prepared by Thermally Induced Phase Separation. Journal of Biomedical Materials Research Part A, 47, 8-17.<8::AID-JBM2>3.0.CO;2-L

[12]   Fouad, H., Elsarnagawy, T., Almajhdi, F.N. and Khalil, K.A. (2013) Preparation and in Vitro Thermo-Mechanical Characterization of Electrospun PLGA Nanofibers for Soft and Hard Tissue Replacement. International Journal of Electrochemical Science, 8, 2293-2304.

[13]   Wang, C. and Wang, M. (2014) Electrospun Multifunctional Tissue Engineering Scaffolds. Frontiers of Materials Science, 8, 3-19.

[14]   Castilho, M., Pires, I., Gouveia, B. and Rodrigues, J. (2011) Structural Evaluation of Scaffolds Prototypes Produced by Three-Dimensional Printing. The International Journal of Advanced Manufacturing Technology, 56, 561-569.

[15]   Lee, E., Koh, Y., Yoon, B., Kim, H. and Kim, H. (2007) Highly Porous Hydroxyapatite Bioceramics with Interconnected Pore Channels Using Camphene-Based Freeze Casting. Materials Letters, 61, 2270-2273.

[16]   Monmaturapoj, N. and Yatongchai, C. (2011) Influence of Preparation Method on Hydroxyapatite Porous Scaffolds. Bulletin of Materials Science, 34, 1733-1737.

[17]   Scalera, F., Gervaso, F., Sanosh, K.P., Sannino, A. and Licciulli, A. (2013) Influence of the Calcination Temperature on Morphological and Mechanical Properties of Highly Porous Hydroxyapatite Scaffolds. Ceramics International, 39, 4839-4846.

[18]   Swain, S.K., Bhattacharyya, S. and Sarkar, D. (2011) Preparation of Porous Scaffold from Hydroxyapatite Powders. Materials Science and Engineering: C, 31, 1240-1244.

[19]   Leong, K.F., Cheah, C.M. and Chua, C.K. (2003) Solid Freeform Fabrication of Three-Dimensional Scaffolds for Engineering Replacement Tissues and Organs. Biomaterials, 24, 2363-2378.

[20]   Ryan, G.E., Pandit, A.S. and Apatsidis, D.P. (2008) Biomaterials Porous Titanium Scaffolds Fabricated Using a Rapid Prototyping and Powder Metallurgy Technique. Biomaterials, 29, 3625-3635.

[21]   Lam, C.X.F., Mo, X.M., Teoh, S.H. and Hutmacher, D.W. (2002) Scaffold Development Using 3D Printing with a Starch-Based Polymer. Materials Science and Engineering: C, 20, 49-56.

[22]   Anselme, K. (2000) Osteoblast Adhesion on Biomaterials. Biomaterials, 21, 667-681.

[23]   Curran, J.M., Chen, R. and Hunt, J.A. (2006) The Guidance of Human Mesenchymal Stem Cell Differentiation in Vitro by Controlled Modifications to the Cell Substrate. Biomaterials, 27, 4783-4793.

[24]   Glass-Brudzinski, J., Perizzolo, D. and Brunette, D.M. (2002) Effects of Substratum Surface Topography on the Organization of Cells and Collagen Fibers in Collagen Gel Cultures. Journal of Biomedical Materials Research Part A, 61, 608-618.

[25]   Kommareddy, K.P., Lange, C., Rumpler, M., Dunlop, J.W.C., Manjubala, I., Cui, J., et al. (2015) Two Stages in Three-Dimensional in Vitro Growth of Tissue Generated by Osteoblastlike Cells. Biointerphases, 5, 45-52.

[26]   Rumpler, M., Woesz, A., Dunlop, J.W.C., Van Dongen, J.T. and Fratzl, P. (2008) The Effect of Geometry on Three-Dimensional Tissue Growth. Journal of the Royal Society Interface, 5, 1173-1180.

[27]   Hollister, S.J. (2005) Porous Scaffold Design for Tissue Engineering. Nature Materials, 4, 518-524.

[28]   Leukers, B., Gulkan, H., Irsen, S.H., Milz, S., Tille, C., Schieker, M., et al. (2005) Hydroxyapatite Scaffolds for Bone Tissue Engineering Made by 3D Printing. Journal of Materials Science: Materials in Medicine, 16, 1121-1124.

[29]   Shanjani, Y., Hu, Y., Pilliar, R.M. and Toyserkani, E. (2011) Mechanical Characteristics of Solid-Freeform-Fabricated Porous Calcium Polyphosphate Structures with Oriented Stacked Layers. Acta Biomaterialia, 7, 1788-1796.

[30]   Klammert, U., Gbureck, U., Vorndran, E., Rodiger, J., Meyer-Marcotty, P. and Kübler, A.C. (2010) 3D Powder Printed Calcium Phosphate Implants for Reconstruction of Cranial and Maxillofacial Defects. Journal of Cranio-Maxillo-Facial Surgery, 38, 565-570.

[31]   Moroni, L. and Elisseeff, J.H. (2008) Biomaterials Engineered for Integration. Materials Today, 11, 44-51.

[32]   Yeong, W., Chua, C., Leong, K. and Chandrasekaran, M. (2004) Rapid Prototyping in Tissue Engineering: Challenges and Potential. Trends in Biotechnology, 22, 643-652.

[33]   Zein, I., Hutmacher, D.W., Cheng, K. and Hin, S. (2002) Fused Deposition Modeling of Novel Scaffold Architectures for Tissue Engineering Applications. Biomaterials, 23, 1169-1185.

[34]   Porter, J.R., Ruckh, T.T. and Popat, K.C. (2009) Bone Tissue Engineering: A Review in Bone Biomimetics and Drug Delivery Strategies. Biotechnology Progress, 25, 1539-1560.

[35]   Bose, S., Vahabzadeh, S. and Bandyopadhyay, A. (2013) Bone Tissue Engineering Using 3D Printing. Materials Today, 16, 496-504.

[36]   Kiebzak, G.M. (1991) Age-Related Bone Changes. Experimental Gerontology, 26, 171-187.

[37]   Santos, C.F.L., Silva, A.P., Lopes, L., Pires, I. and Correia, I.J. (2012) Design and Production of Sintered β-Tricalcium Phosphate 3D Scaffolds for Bone Tissue Regeneration. Materials Science and Engineering: C, 32, 1293-1298.

[38]   Currey, J.D. (2004) Tensile Yield in Compact Bone Is Determined by Strain, Post-Yield Behaviour by Mineral Content. Journal of Biomechanics, 37, 549-556.

[39]   Sturm, S., Zhou, S., Mai, Y.W. and Li, Q. (2010) On Stiffness of Scaffolds for Bone Tissue Engineering—A Numerical Study. Journal of Biomechanics, 43, 1738-1744.

[40]   Arealis, G. and Nikolaou, V.S. (2015) Bone Printing: New Frontiers in the Treatment of Bone Defects. Injury, 46, S20-S22.

[41]   Wang, P., Zhao, L., Liu, J., Weir, M.D., Zhou, X. and Xu, H.H.K. (2014) Bone Tissue Engineering via Nanostructured Calcium Phosphate Biomaterials and Stem Cells. Bone Research, 2, 14017-14030.

[42]   Giannoudis, P., Dinopoulos, H. and Tsiridis, E. (2005) Bone Substitutes: An Update. Injury, 36, S20-S27.

[43]   Laurencin, C., Khan, Y. and El-Amin, S.F. (2006) Bone Graft Substitutes. Expert Review of Medical Devices, 3, 49-57.

[44]   Navarro, M., Michiardi, A., Castan, O. and Planell, J.A. (2008) Biomaterials in Orthopaedics. Journal of the Royal Society Interface, 5, 1137-1158.

[45]   Fuchs, J.R., Nasseri, B.A. and Vacanti, J.P. (2001) Tissue Engineering: A 21st Century Solution to Surgical Reconstruction. The Annals of Thoracic Surgery, 72, 577-591.

[46]   Chaignaud, B.E., Langer, R. and Vacanti, J.P. (1996) Polymer Scaffolds and Cells. 1-14.

[47]   Kim, D.H., Rhim, R., Li, L., Martha, J., Swaim, B.H., Banco, R.J., et al. (2009) Prospective Study of Iliac Crest Bone Graft Harvest Site Pain and Morbidity. The Spine Journal, 9, 886-892.

[48]   Kroeze, R.J., Helder, M.N., Govaert, L.E. and Smit, T.H. (2009) Biodegradable Polymers in Bone Tissue Engineering. Materials (Basel), 2, 833-856.

[49]   Naughton, G.K., Tolbert, W.R. and Grillot, T.M. (1995) Emerging Developments in Tissue Engineering and Cell Technology. Tissue Engineering, 1, 211-219.

[50]   Duan, B. and Wang, M. (2010) Customized Ca-P/PHBV Nanocomposite Scaffolds for Bone Tissue Engineering: Design, Fabrication, Surface Modification and Sustained Release of Growth Factor. Journal of the Royal Society Interface, 7, 615-629.

[51]   Rezwan, K., Chen, Q.Z., Blaker, J.J. and Roberto, A. (2006) Biodegradable and Bioactive Porous Polymer/Inorganic Composite Scaffolds for Bone Tissue Engineering. Biomaterials, 27, 3413-3431.

[52]   Salgado, A.J., Coutinho, O.P. and Reis, R.L. (2004) Bone Tissue Engineering: State of the Art and Future Trends. Macromolecular Bioscience, 4, 743-765.

[53]   Griffith, L.G. (2002) Tissue Engineering—Current Challenges and Expanding Opportunities. Science, 295, 1009-1014.

[54]   Cox, S.C., Thornby, J.A., Gibbons, G.J., Williams, M.A. and Mallick, K.K. (2015) 3D Printing of Porous Hydroxyapatite Scaffolds Intended for Use in Bone Tissue Engineering Applications. Materials Science and Engineering: C, 47, 237-247.

[55]   Li, X., Wang, L., Fan, Y., Feng, Q., Cui, F. and Watari, F. (2013) Nanostructured Scaffolds for Bone Tissue Engineering. Journal of Biomedical Materials Research Part A, 101, 2424-2435.

[56]   Kuboki, Y., Takita, H., Kobayashi, D., Tsuruga, E., Inoue, M., Murata, M., et al. (1998) BMP-Induced Osteogenesis on the Surface of Hydroxyapatite with Geometrically Feasible and Nonfeasible Structures: Topology of Osteogenesis. Journal of Biomedical Materials Research Part A, 39, 190-199.<190::AID-JBM4>3.0.CO;2-K

[57]   Woo, K.M., Chen, V.J. and Ma, P.X. (2003) Nano-Fibrous Scaffolding Architecture Selectively Enhances Protein Adsorption Contributing to Cell Attachment. Journal of Biomedical Materials Research Part A, 67, 531-537.

[58]   Igual, R., Medrano, C. and Plaza, I. (2013) Challenges, Issues and Trends in Fall Detection Systems. BioMedical Engineering OnLine, 12, 66.

[59]   Macchetta, A., Turner, I.G. and Bowen, C.R. (2009) Fabrication of HA/TCP Scaffolds with a Graded and Porous Structure Using a Camphene-Based Freeze-Casting Method. Acta Biomaterialia, 5, 1319-1327.

[60]   Chen, Q., Roether, J.A. and Boccaccini, A.R. (2008) Tissue Engineering Scaffolds from Bioactive Glass and Composite Materials. Topics in Tissue Engineering, 4, 1-27.

[61]   Lin, H., Zhang, D., Alexander, P.G., Yang, G., Tan, J., Wai-Ming, A., et al. (2014) Application of Visible Light-Based Projection Stereolithography for Live Cell-Scaffold Fabrication with Designed Architecture. Biomaterials, 34, 331-339.

[62]   Murphy, S.V. and Atala, A. (2014) 3D Bioprinting of Tissues and Organs. Nature Biotechnology, 32, 773-785.

[63]   Tarafder, S., Banerjee, S., Bandyopadhyay, A. and Bose, S. (2011) Electrically Polarized Biphasic Calcium Phosphates: Adsorption and Release of Bovine Serum Albumin. Langmuir, 26, 16625-16629.

[64]   Rechendorff, K., Hovgaard, M.B., Foss, M., Zhdanov, V.P. and Besenbacher, F. (2006) Enhancement of Protein Adsorption Induced by Surface Roughness. Langmuir, 22, 10885-10888.

[65]   Martin, J.Y., Schwartz, Z., Hummert, T.W., Schraub, D.M., Simpson, J., Lankford, J., et al. (1995) Effect of Titanium Surface Roughness on Proliferation, Differentiation, and Protein Synthesis of Human Osteoblast-Like Cells (MG63). Journal of Biomedical Materials Research Part A, 29, 389-401.

[66]   Yuan, H., Yang, Z., Li, Y., Zhang, X., De Bruijn, J.D. and De Groot, K. (1998) Osteoinduction by Calcium Phosphate Biomaterials. Journal of Materials Science: Materials in Medicine, 9, 723-726.

[67]   Barradas, A.M.C., Yuan, H., van Blitterswijk, C.A. and Habibovic, P. (2011) Osteoinductive Biomaterials: Current Knowledge of Properties, Experimental Models and Biological Mechanisms. European Cells & Materials, 21, 407-429.

[68]   Chang, P., Liu, B., Liu, C., Chou, H., Ho, M., Liu, H., et al. (2007) Bone Tissue Engineering with Novel rhBMP2-PLLA Composite Scaffolds. Journal of Biomedical Materials Research Part A, 81, 771-780.

[69]   Perez, R.A. and Mestres, G. (2015) Role of Pore Size and Morphology in Musculo-Skeletal Tissue Regeneration. Materials Science and Engineering: C, 61, 922-939.

[70]   Lee, J.W., Ahn, G., Cho, D.W. and Kim, J.Y. (2010) Evaluating Cell Proliferation Based on Internal Pore Size and 3D Scaffold Architecture Fabricated Using Solid Freeform Fabrication Technology. Journal of Materials Science: Materials in Medicine, 21, 3195-3205.

[71]   Lim, T.C., Chian, K.S. and Leong, K.F. (2010) Cryogenic Prototyping of Chitosan Scaffolds with Controlled Micro and Macro Architecture and Their Effect on in Vivo Neo-Vascularization and Cellular Infiltration. Journal of Biomedical Materials Research Part A, 94, 1303-1311.

[72]   Gbureck, U., Holzel, T., Doillon, C.J., Müller, F.A. and Barralet, J.E. (2007) Direct Printing of Bioceramic Implants with Spatially Localized Angiogenic Factors. Advanced Materials, 19, 795-800.

[73]   Jonathan, G. and Karim, A. (2016) 3D Printing in Pharmaceutics: A New Tool for Designing Customized Drug Delivery Systems. International Journal of Pharmaceutics, 499, 376-394.

[74]   Gittens, S. and Uludag, H. (2001) Growth Factor Delivery for Bone Tissue Engineering. Journal of Drug Targeting, 9, 407-429.

[75]   Groeneveld, E.H.J., Van Den Bergh, J.P.A., Holzmann, P., Ten Bruggenkate, C.M., Tuinzing, D.B. and Burger, E.H. (1999) Mineralization Processes in Demineralized Bone Matrix Grafts in Human Maxillary Sinus Floor Elevations. Journal of Biomedical Materials Research Part A, 48, 393-402.<393::AID-JBM1>3.0.CO;2-C

[76]   Hench, L.L. and Polak, J.M. (2002) Third-Generation Biomedical Materials. Science, 295, 1014-1017.

[77]   Luginbuehl, V., Meinel, L., Merkle, H.P. and Gander, B. (2004) Localized Delivery of Growth Factors for Bone Repair. European Journal of Pharmaceutics and Biopharmaceutics, 58, 197-208.

[78]   Tsivintzelis, I., Marras, S.I., Zuburtikudis, I. and Panayiotou, C. (2007) Porous Poly(L-Lactic Acid) Nanocomposite Scaffolds Prepared by Phase Inversion Using Supercritical CO2 as Antisolvent. Polymer (Guildf), 48, 6311-6318.

[79]   Serra, T., Planell, J.A. and Navarro, M. (2013) High-Resolution PLA-Based Composite Scaffolds via 3-D Printing Technology. Acta Biomaterialia, 9, 5521-5530.

[80]   Arifin, A., Sulong, A.B., Muhamad, N., Syarif, J. and Ramli, M.I. (2014) Material Processing of Hydroxyapatite and Titanium Alloy (HA/Ti) Composite as Implant Materials Using Powder Metallurgy: A Review. Materials & Design, 55, 165-175.

[81]   Ben-Nissan, B. (2007) Natural Bioceramics: From Coral to Bone and Beyond. Current Opinion in Solid State and Materials Science, 7, 283-288.

[82]   Franco, J., Hunger, P., Launey, M.E., Tomsia, A.P. and Saiz, E. (2010) Direct Write Assembly of Calcium Phosphate Scaffolds Using a Water-Based Hydrogel. Acta Biomaterialia, 6, 218-228.

[83]   Fu, Q., Saiz, E. and Tomsia, A.P. (2011) Direct Ink Writing of Highly Porous and Strong Glass Scaffolds for Load-Bearing Bone Defects Repair and Regeneration. Acta Biomaterialia, 7, 3547-3554.

[84]   Kim, H., Knowles, J.C. and Kim, H. (2004) Hydroxyap-atite/Poly(ε-Caprolactone) Composite Coatings on Hydroxyapatite Porous Bone Scaffold for Drug Delivery. Biomaterials, 25, 1279-1287.

[85]   Martínez-Pérez, C.A., García-Montelongo, J., Garcia, P.E., Farias-Mancilla, J.R. and Monreal, H. (2012) Preparation of Hydroxyapatite Nanoparticles Facilitated by the Presence of β-Cyclodextrin. Journal of Alloys and Compounds, 536, S432-S436.

[86]   Moradi, A., Dalilottojari, A., Pingguan-Murphy, B. and Djordjevic, I. (2013) Fabrication and Characterization of Elastomeric Scaffolds Comprised of a Citric Acid-Based Polyester/Hydroxyapatite Microcomposite. Materials & Design, 50, 446-450.

[87]   Rajzer, I. (2014) Fabrication of Bioactive Polycaprolactone/Hydroxyapatite Scaffolds with Final Bilayer Nano-/Micro-Fibrous Structures for Tissue Engineering Application. Journal of Materials Science, 49, 5799-5807.

[88]   Sebdani, M.M. and Fathi, M.H. (2011) Novel Hydroxyapatite-Forsterite-Bioglass Nanocomposite Coatings with Improved Mechanical Properties. Journal of Alloys and Compounds, 509, 2273-2276.

[89]   Vallet-Regí, M. and González-Calbet, J.M. (2004) Calcium Phosphates as Substitution of Bone Tissues. Progress in Solid State Chemistry, 32, 1-31.

[90]   Boccaccini, A.R., Blaker, J.J., Maquet, V., Day, R.M. and Je, R. (2005) Preparation and Characterization of Poly(Lactide-co-Glycolide) (PLGA) and PLGA/Bioglass? Composite Tubular foam Scaffolds for Tissue Engineering Applications. Materials Science and Engineering: C, 25, 23-31.

[91]   Hench, L.L. (1998) Feature 1705. Stress: The International Journal on the Biology of Stress, 81, 1705-1728.

[92]   Senatov, F.S., Niaza, K.V., Zadorozhnyy, M.Y., Maksimkin, A.V., Kaloshkin, S.D. and Estrin, Y.Z. (2016) Mechanical Properties and Shape Memory Effect of 3D-Printed PLA-Based Porous Scaffolds. Journal of the Mechanical Behavior of Biomedical Materials, 57, 139-148.

[93]   Zhang, R. and Ma, P.X. (2004) Biomimetic Polymer/Apatite Composite Scaffolds for Mineralized Tissue Engineering. Macromolecular Bioscience, 4, 100-111.

[94]   Raghoebar, G.M., Liem, R.S.B., Bos, R.R.M., Van Der Wal, J.E. and Vissink, A. (2006) Resorbable Screws for Fixation of Autologous Bone Grafts. Clinical Oral Implants Research, 17, 288-293.

[95]   Kim, K.K. and Pack, D.W. (2006) Microspheres for Drug Delivery. In: Ferrari, M., Lee, A.P. and Lee, L.J., Eds., BioMEMS and Biomedical Nanotechnology, Springer, New York, 19-50.

[96]   Lassalle, V. and Ferreira, M.L. (2007) PLA Nano- and Microparticles for Drug Delivery: An Overview of the Methods of Preparation. Macromolecular Bioscience, 7, 767-783.

[97]   Mora-Huertas, C.E., Fessi, H. and Elaissari, A. (2010) Polymer-Based Nanocapsules for Drug Delivery. International Journal of Pharmaceutics 385, 113-142.

[98]   Ouchi, T., Saito, T., Kontani, T. and Ohya, Y. (2004) Encapsulation and/or Release Behavior of Bovine Serum Albumin within and from Polylactide-Grafted Dextran Microspheres. Macromolecular Bioscience, 4, 458-463.

[99]   Vilar, G., Tulla-Puche, J. and Albericio, F. (2012) Polymers and Drug Delivery Systems. Current Drug Delivery, 9, 367-394.

[100]   Shah Mohammadi, M., Bureau, M.N. and Nazhat, S.N. (2014) Polylactic Acid (PLA) Biomedical Foams for Tissue Engineering. In: Netti, P., Ed., Biomedical Foams for Tissue Engineering Applications, Woodhead Publishing Limited, Cambridge, 313-334.

[101]   Tanodekaew, S., Channasanon, S. and Kaewkong, P. (2013) PLA-HA Scaffolds: Preparation and Bioactivity. Procedia Engineering, 59, 144-149.

[102]   Bonfield, W. (2006) Designing Porous Scaffolds for Tissue Engineering. Philosophical Transactions of the Royal Society A, 364, 227-232.

[103]   Pérez, R.A., Won, J., Knowles, J.C. and Kim, H. (2013) Naturally and Synthetic Smart Composite Biomaterials for Tissue Regeneration. Advanced Drug Delivery Reviews, 65, 471-496.

[104]   Wegst, U.G.K. and Ashby, M.F. (2004) The Mechanical Efficiency of Natural Materials. Philosophical Magazine, 21, 2167-2181.

[105]   Venugopal, J., Prabhakaran, M.P., Zhang, Y., Low, S., Choon, A.T. and Ramakrishna, S. (2010) Biomimetic Hydroxyapatite-Containing Composite Nanofibrous Substrates for Bone Tissue Engineering. Philosophical Transactions of the Royal Society A, 368, 2065-2081.

[106]   Van Vlierberghe, S., Dubruel, P. and Schacht, E. (2011) Biopolymer-Based Hydrogels as Scaffolds for Tissue Engineering Applications: A Review. Biomacromolecules, 12, 1387-1408.

[107]   Ray, S.S. and Okamoto, M. (2003) Polymer/Layered Silicate Nanocomposites: A Review from Preparation to Processing. Progress in Polymer Science, 28, 1539-1641.

[108]   Armentano, I., Bitinis, N., Fortunati, E., Mattioli, S., Rescignano, N., Verdejo, R., et al. (2013) Multifunctional Nanostructured PLA Materials for Packaging and Tissue Engineering. Progress in Polymer Science, 38, 1720-1747.

[109]   Zhang, L. and Webster, T.J. (2009) Nanotechnology and Nanomaterials: Promises for Improved Tissue Regeneration. Nano Today, 4, 66-80.

[110]   Karageorgiou, V. and Kaplan, D. (2005) Porosity of 3D Biomaterial Scaffolds and Osteogenesis. Biomaterials, 26, 5474-5491.

[111]   Kubinová, S. and Syková, E. (2010) Nanotechnologies in Regenerative Medicine. Minimally Invasive Therapy & Allied Technologies, 19, 144-156.

[112]   Hule, R.A. and Pochan, D.J. (2007) Polymer Nanocomposites for Biomedical. MRS Bulletin, 32, 354-358.

[113]   Murugan, R. and Ramakrishna, S. (2005) Development of Nanocomposites for Bone Grafting. Composites Science and Technology, 65, 2385-2406.

[114]   Tjong, S.C. (2006) Structural and Mechanical Properties of Polymer Nanocomposites. Materials Science and Engineering: R: Reports, 53, 73-197.

[115]   Cho, J., Joshi, M.S. and Sun, C.T. (2006) Effect of Inclusion Size on Mechanical Properties of Polymeric Composites with Micro and Nano Particles. Composites Science and Technology, 66, 1941-1952.

[116]   Jo, J., Lee, E., Shin, D., Kim, H., Kim, H., Koh, Y., et al. (2009) In Vitro/in Vivo Biocompatibility and Mechanical Properties of Bioactive Glass Nanofiber and Poly(ε-Caprolactone) Composite Materials. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 91, 213-220.

[117]   Davis, H.E. and Leach, J.K. (2008) Hybrid and Composite Biomaterials in Tissue Engineering. In: Ashammakhi, N, Ed., Topics in Multifunctional Biomaterials and Devices, 1-26.

[118]   Bulte, J.W.M., Douglas, T., Witwer, B., Zhang, S., Strable, E., Lewis, B.K., et al. (2001) Magnetodendrimers Allow Endosomal Magnetic Labeling and in Vivo Tracking of Stem Cells. Nature Biotechnology, 19, 1141-1147.

[119]   Harrison, B.S. and Atala, A. (2007) Carbon Nanotube Applications for Tissue Engineering. Biomaterials, 28, 344-353.

[120]   Gleiter, H. (2000) Nanostructured Materials: Basic Concepts and Microstructure. Acta Materialia, 48, 1-29.

[121]   Mothersill, C., Seymour, C.B. and O’Brien, A. (1991) Induction of c-Myc Oncoprotein and of Cellular Proliferation by Radiation in Normal Human Urothelial Cultures. Anticancer Research, 11, 1609-1612.

[122]   Billiet, T., Vandenhaute, M., Schelfhout, J., Van Vlierberghe, S. and Dubruel, P. (2012) A Review of Trends and Limitations in Hydrogel-Rapid Prototyping for Tissue Engineering. Biomaterials, 33, 6020-6041.

[123]   Butscher, A., Bohner, M., Roth, C., Ernstberger, A., Heuberger, R., Doebelin, N., et al. (2012) Printability of Calcium Phosphate Powders for Three-Dimensional Printing of Tissue Engineering Scaffolds. Acta Biomaterialia, 8, 373-385.

[124]   Chumnanklang, R., Panyathanmaporn, T., Sitthiseripratip, K. and Suwanprateeb, J. (2007) 3D Printing of Hydroxyapatite: Effect of Binder Concentration in Pre-Coated Particle on Part Strength. Materials Science and Engineering: C, 27, 914-921.

[125]   Kumar, S. and Kruth, J. (2010) Composites by Rapid Prototyping Technology. Materials & Design, 31, 850-856.

[126]   Maleksaeedi, S., Eng, H., Wiria, F.E., Ha, T.M.H. and He, Z. (2014) Property Enhancement of 3D-Printed Alumina Ceramics Using Vacuum Infiltration. Journal of Materials Processing Technology, 214, 1301-1306.

[127]   Kietzmann, J., Pitt, L. and Berthon, P. (2015) Disruptions, Decisions, and Destinations: Enter the Age of 3-D Printing and Additive Manufacturing. Business Horizons, 58, 209-215.

[128]   Stansbury, J.W. and Idacavage, M.J. (2015) 3D Printing with Polymers: Challenges among Expanding Options and Opportunities. Dental Materials, 32, 54-64.

[129]   Berman, B., Zarb, F.G. and Hall, W. (2012) 3-D Printing: The New Industrial Revolution. Business Horizons, 55, 155-162.

[130]   Melchels, F.P.W., Feijen, J. and Grijpma, D.W. (2010) A Review on Stereolithography and Its Applications in Biomedical Engineering. Biomaterials, 31, 6121-6130.

[131]   Stickland, M.T., Mckay, S. and Scanlon, T.J. (2003) The Development of a Three Dimensional Imaging System and Its Application in Computer Aided Design Workstations. Mechatronics, 13, 521-532.

[132]   Watson, R.A. (2014) A Low-Cost Surgical Application of Additive Fabrication. Journal of Surgical Education, 71, 14-17.

[133]   Gebler, M., Uiterkamp, A.J.M.S. and Visser, C. (2014) A Global Sustainability Perspective on 3D Printing Technologies. Energy Policy, 74, 158-167.

[134]   Shafiee, A. and Atala, A. (2016) Printing Technologies for Medical Applications. Trends in Molecular Medicine, 22, 254-265.

[135]   Yan, X. and Gu, P. (1996) A Review of Rapid Prototyping Technologies and Systems. Computer-Aided Design, 28, 307-316.

[136]   Yang, S., Yang, H., Chi, X., Evans, J.R.G., Thompson, I., Cook, R.J., et al. (2008) Rapid Prototyping of Ceramic Lattices for Hard Tissue Scaffolds. Materials & Design, 29, 1802-1809.

[137]   Rezende, R.A., Kasyanov, V., Mironov, V. and Lopes, J.V. (2015) Organ Printing as an Information Technology. Procedia Engineering, 110, 151-158.

[138]   Malik, H.H., Darwood, A.R.J., Hons, B., Shaunak, S., Kulatilake, P., Elhilly, A.A., et al. (2015) Three-Dimensional Printing in Surgery: A Review of Current Surgical Applications. Journal of Surgical Research, 199, 512-522.

[139]   Pati, F., Shim, J., Lee, J. and Cho, D. (2013) 3D Printing of Cell-Laden Constructs for Heterogeneous Tissue Regeneration. Manufacturing Letters, 1, 49-53.

[140]   Zhang, W., Lian, Q., Li, D., Wang, K., Hao, D., Bian, W., et al. (2015) The Effect of Interface Microstructure on Interfacial Shear Strength for Osteochondral Scaffolds Based on Biomimetic Design and 3D Printing. Materials Science and Engineering: C, 46, 10-15.

[141]   Kruth, J., Levy, G., Klocke, F. and Childs, T.H.C. (2007) Consolidation Phenomena in Laser and Powder-Bed Based Layered Manufacturing. CIRP Annals—Manufacturing Technology, 56, 730-759.

[142]   Melchels, F.P.W., Feijen, J. and Grijpma, D.W. (2009) A Poly(D,L-Lactide) Resin for the Preparation of Tissue Engineering Scaffolds by Stereolithography. Biomaterials, 30, 3801-3809.

[143]   De Ciurana, J., Serenó, L. and Vallès, è. (2013) Selecting Process Parameters in RepRap Additive Manufacturing System for PLA Scaffolds Manufacture. Procedia CIRP, 5, 152-157.

[144]   Gauvin, R., Chen, Y., Woo, J., Soman, P., Zorlutuna, P., Nichol, J.W., et al. (2012) Biomaterials Microfabrication of Complex Porous Tissue Engineering Scaffolds Using 3D Projection Stereolithography. Biomaterials, 33, 3824-3834.

[145]   Okabe, K., Yamada, Y., Ito, K., Kohgo, T., Yoshimi, R. and Ueda, M. (2009) Injectable Soft-Tissue Augmentation by Tissue Engineering and Regenerative Medicine with Human Mesenchymal Stromal Cells, Platelet-Rich Plasma and Hyaluronic Acid Scaffolds. Cytotherapy, 11, 307-316.

[146]   Kim, S.S., Utsunomiya, H., Koski, J.A., Wu, B.M., Cima, M.J., Sohn, J., et al. (1998) Survival and Function of Hepatocytes on a Novel Three-Dimensional Synthetic Biodegradable Polymer Scaffold with an Intrinsic Network of Channels. Annals of Surgery, 228, 8-13.

[147]   Park, J.S., Chu, J.S., Tsou, A.D., Diop, R., Wang, A. and Li, S. (2012) The Effect of Matrix Stiffness on the Differentiation of Mesenchymal Stem Cells in Response to TGF-β. Biomaterials, 32, 3921-3930.

[148]   Zeltinger, J., Sherwood, J.K., Graham, D.A., Müeller, R. and Griffith, L.G. (2001) Effect of Pore Size and Void Fraction on Cellular Adhesion, Proliferation, and Matrix Deposition. Tissue Engineering, 7, 557-572.

[149]   Seliktar, D., Dikovsky, D. and Napadensky, E. (2013) Bioprinting and Tissue Engineering: Recent Advances and Future Perspectives. Israel Journal of Chemistry, 53, 795-804.

[150]   Tang, D., Tare, R.S., Yang, L., Williams, D.F., Ou, K. and Oreffo, R.O.C. (2016) Biofabrication of Bone Tissue: Approaches, Challenges and Translation for Bone Regeneration. Biomaterials, 83, 363-382.

[151]   Odde, D.J. and Renn, M.J. (1999) Laser-Guided Direct Writing for Applications in Biotechnology. Nanotechnology, 7799, 385-389.

[152]   Boland, T., Mironov, V., Gutowska, A., Roth, E.A. and Markwald, R.R. (2003) Cell and Organ Printing 2: Fusion of Cell Aggregates in Three-Dimensional Gels. The Anatomical Record, 272A, 497-502.

[153]   Saunders, R., Bosworth, L., Gough, J., Derby, B., Reis, N., Materials, E., et al. (2004) Selective Cell Delivery for 3D Tissue Culture and Engineering. European Cells & Materials, 7, 84.

[154]   Yang, S., Leong, K.-F., Du, Z. and Chua, C.-K. (2002) The Design of Scaffolds for Use in Tissue Engineering. Part II. Rapid Prototyping Techniques. Tissue Engineering, 8, 1-11.

[155]   Beahm, E.K., Walton, R.L. and Patrick, C.W. (2003) Progress in Adipose Tissue Construct Development. Clinics in Plastic Surgery, 30, 547-558.

[156]   Lee, Y.B., Polio, S., Lee, W., Dai, G. and Yoo, S. (2010) Bio-Printing of Collagen and VEGF-Releasing Fibrin Gel Scaffolds for Neural Stem Cell Culture. Experimental Neurology, 223, 645-652.

[157]   Shim, J., Kim, S.E., Park, J.Y. and Kundu, J. (2014) Scaffolds with Long-Term Delivery for Enhanced Bone Regeneration in a Rabbit Diaphyseal Defect. Tissue Engineering Part A, 20, 1980-1992.

[158]   Flynn, L.E. (2010) The Use of Decellularized Adipose Tissue to Provide an Inductive Microenvironment for the Adipogenic Differentiation of Human Adipose-Derived Stem Cells. Biomaterials, 31, 4715-4724.

[159]   Gilbert, T.W., Sellaro, T.L. and Badylak, S.F. (2006) Decellularization of Tissues and Organs. Biomaterials, 27, 3675-3683.

[160]   Pati, F., Ha, D., Jang, J., Ho, H. and Rhie, J. (2015) Biomimetic 3D Tissue Printing for Soft Tissue Regeneration. Biomaterials, 62, 164-175.

[161]   Debnath, J. and Brugge, J.S. (2005) Modelling Glandular Epithelial Cancers in Three Dimensional Cultures. Nature Reviews Cancer, 5, 675-688.

[162]   Vargo-gogola, T. and Rosen, J.M. (2007) Modelling Breast Cancer: One Size Does Not Fit All. Nature Reviews Cancer, 7, 659-672.

[163]   Rijal, G. and Li, W. (2016) 3D Scaffolds in Breast Cancer Research. Biomaterials, 81, 135-156.

[164]   Xu, T., Zhao, W., Zhu, J., Albanna, M.Z., Yoo, J.J. and Atala, A. (2013) Biomaterials Complex Heterogeneous Tissue Constructs Containing Multiple Cell Types Prepared by Inkjet Printing Technology. Biomaterials, 34, 130-139.

[165]   Lee, V.K., Lanzi, A.M., Ngo, H., Loo, S.C., Vincent, P.A. and Dai, G. (2014) Generation of Multi-Scale Vascular Network System Within 3D Hydrogel Using 3D Bio-Printing Technology. Cellular and Molecular Bioengineering, 7, 460-472.

[166]   Paulsen, S.J. and Miller, J.S. (2015) Tissue Vascularization through 3D Printing: Will Technology Bring Us Flow? Developmental Dynamics, 244, 629-640.

[167]   Hopkinson, N. and Dickens, P.M. (2006) Rapid Manufacturing: An Industrial for the Digital Age.

[168]   Chua, C.K., Leong, K.F., Tan, K.H., Wiria, F.E. and Cheah, C.M. (2004) Development of Tissue Scaffolds Using Selective Laser Sintering of Polyvinyl Alcohol/Hydroxyapatite Biocomposite for Craniofacial and Joint Defects. Journal of Materials Science: Materials in Medicine, 15, 1113-1121.

[169]   Shuai, C., Gao, C., Nie, Y., Hu, H., Zhou, Y. and Peng, S. (2011) Structure and Properties of Nano-Hydroxypatite Scaffolds for Bone Tissue Engineering with a Selective Laser Sintering System. Nanotechnology, 22, 285703.

[170]   Tan, K.H., Chua, C.K., Leong, K.F., Cheah, C.M., Cheang, P., Bakar, M.S.A., et al. (2003) Scaffold Development Using Selective Laser Sintering of Polyetheretherketone-Hydroxyapatite Biocomposite Blends. Biomaterials, 24, 3115- 3123.

[171]   Soe, S.P., Eyers, D.R. and Setchi, R. (2013) Assessment of Non-Uniform Shrinkage in the Laser Sintering of Polymer Materials. The International Journal of Advanced Manufacturing Technology, 68, 111-125.

[172]   Dupin, S., Lame, O., Barrès, C. and Charmeau, J. (2012) Microstructural Origin of Physical and Mechanical Properties of Polyamide 12 Processed by Laser Sintering. European Polymer Journal, 48, 1611-1621.

[173]   Butscher, A., Bohner, M., Hofmann, S., Gauckler, L. and Müller, R. (2011) Structural and Material Approaches to Bone Tissue Engineering in Powder-Based Three-Dimensional Printing. Acta Biomaterialia, 7, 907-920.

[174]   Hull, C.W. and UVP, Inc. (1986) Apparatus for Production of Three-Dimensional Objects by Stereolithography. US Pat 4575330.

[175]   Gittard, S.D. and Narayan, R.J. (2011) Laser Direct Writing of Micro- and Nano-Scale Medical Devices. Expert Review of Medical Devices, 7, 343-356.

[176]   Selimis, A., Mironov, V. and Farsari, M. (2015) Microelectronic Engineering Direct Laser Writing: Principles and Materials for Scaffold 3D Printing. Microelectronic Engineering, 132, 83-89.

[177]   Cooke, M.N., Fisher, J.P., Dean, D., Rimnac, C. and Mikos, A.G. (2002) Use of Stereolithography to Manufacture Critical-Sized 3D Biodegradable Scaffolds for Bone Ingrowth. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 64, 65-69.

[178]   Fisher, J.P., Vehof, J.W.M., Dean, D., Van der Waerden, J.P.C.M., Holland, T.A., Mikos, A.G., et al. (2002) Soft and Hard Tissue Response to Photocrosslinked Poly(Propylene Fumarate) Scaffolds in a Rabbit Model. Journal of Biomedical Materials Research Part A, 59, 547-556.

[179]   Mapili, G., Lu, Y., Chen, S. and Roy, K. (2005) Laser-Layered Microfabrication of Spatially Patterned Functionalized Tissue-Engineering Scaffolds. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 75, 414-424.

[180]   Ikehata, H., Ono, T., Uv, U. and Tls, U.V.A. (2011) The Mechanisms of UV Mutagenesis. Journal of Radiation Research, 52, 115-125.

[181]   Seol, Y., Park, D.Y., Park, J.Y., Kim, S.W. and Park, S.J. (2013) A New Method of Fabricating Robust Freeform 3D Ceramic Scaffolds for Bone Tissue Regeneration. Biotechnology and Bioengineering, 110, 1444-1455.

[182]   Shor, L. (2007) Fabrication of Three-Dimensional Polycaprolactone/Hydroxyapatite Tissue Scaffolds and Osteoblast-Scaffold Interactions in Vitro. Biomaterials, 28, 5291-5297.

[183]   Postiglione, G., Natale, G., Griffini, G., Levi, M. and Turri, S. (2015) Conductive 3D Microstructures by Direct 3D Printing Of Polymer/Carbon Nanotube Nanocomposites via Liquid Deposition Modeling. Composites Part A: Applied Science and Manufacturing, 76, 110-114.

[184]   Hunt, E.J., Zhang, C., Anzalone, N. and Pearce, J.M. (2015) Resources, Conservation and Recycling Polymer Recycling Codes for Distributed Manufacturing with 3-D Printers. Resources, Conservation and Recycling, 97, 24-30.

[185]   Moroni, L., De Wijn, J.R. and Van Blitterswijk, C.A. (2006) 3D Fiber-Deposited Scaffolds for Tissue Engineering: Influence of Pores Geometry and Architecture on Dynamic Mechanical Properties. Biomaterials, 27, 974-985.

[186]   Guo, S., Gosselin, F., Guerin, N., Lanouette, A., Heuzey, M. and Therriault, D. (2013) Solvent-Cast Three-Dimensional Printing of Multifunctional Microsystems. Small, 9, 4118-4122.

[187]   Bergmann, C., Lindner, M., Zhang, W., Koczur, K., Kirsten, A., Telle, R., et al. (2010) 3D Printing of Bone Substitute Implants Using Calcium Phosphate and Bioactive Glasses. Journal of the European Ceramic Society, 30, 2563-2537.

[188]   Vaezi, M. and Chua, C.K. (2011) Effects of Layer Thickness and Binder Saturation Level Parameters on 3D Printing Process. The International Journal of Advanced Manufacturing Technology, 53, 275-284.

[189]   Boland, T., Xu, T., Damon, B. and Cui, X. (2006) Application of Inkjet Printing to Tissue Engineering. Biotechnology Journal, 9, 910-917.

[190]   Chia, H.N. and Wu, B.M. (2015) Recent Advances in 3D Printing of Biomaterials. Journal of Biological Engineering, 9, 4.

[191]   Nakamura, M., Kobayashi, A., Takagi, F., Watanabe, A., Hiruma, Y., Ohuchi, K., et al. (2005) Biocompatible Inkjet Printing Technique for Designed Seeding of Individual Living Cells. Tissue Engineering, 11, 1658-1666.

[192]   Lee, M., Dunn, J.C.Y. and Wu, B.M. (2005) Scaffold Fabrication by Indirect Three-Dimensional Printing. Biomaterials, 26, 4281-4289.

[193]   Wu, B.M., Borland, S.W., Giordano, R.A., Cima, L.G., Sachs, E.M. and Cima, M.J. (1996) Solid Free-Form Fabrication of Drug Delivery Devices. Journal of Controlled Release, 40, 77-87.

[194]   Asadi-eydivand, M., Solati-hashjin, M. and Farzad, A. (2016) Robotics and Computer-Integrated Manufacturing Effect of Technical Parameters on Porous Structure and Strength of 3D Printed Calcium Sulfate Prototypes. Robotics and Computer-Integrated Manufacturing, 37, 57-67.

[195]   Chu, T.G., Hollister, S.J., Halloran, J.W. and Feinberg, S.E. (2002) Manufacturing and Characterization of 3-D Hydroxyapatite Bone Tissue Engineering. Annals of the New York Academy of Sciences, 117, 114-117.

[196]   Liu, C., Xia, Z., Triffitt, J., Hulley, P.A. and Czernuska, J.T. (2008) Novel 3D Collagen Scaffolds Fabricated by Indirect Printing Technique for Tissue Engineering. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 85, 519-528.

[197]   Taboas, J.M., Maddox, R.D., Krebsbach, P.H. and Hollister, S.J. (2003) Indirect Solid Free form Fabrication of Local and Global Porous, Biomimetic and Composite 3D Polymer-Ceramic Scaffolds. Biomaterials, 24, 181-194.

[198]   Tamjid, E. and Simchi, A. (2015) Fabrication of a Highly Ordered Hierarchically Designed Porous Nanocomposite via Indirect 3D Printing: Mechanical Properties and in Vitro Cell Responses. Materials & Design, 88, 924-931.

[199]   Deisinger, U., Hamisch, S., Schumacher, M., Uhl, F., Detsch, R. and Ziegler, G. (2008) Fabrication of Tailored Hydroxyapatite Scaffolds: Comparison between a Direct and an Indirect Rapid Prototyping Technique. Key Engineering Materials, 361-363, 915-918.

[200]   Lu, K., Hiser, M. and Wu, W. (2009) Effect of Particle Size on Three Dimensional Printed Mesh Structures. Powder Technology, 192, 178-183.

[201]   Turker, M., Godlinski, D. and Petzoldt, F. (2008) Effect of Production Parameters on the Properties of IN 718 Superalloy by Three-Dimensional Printing. Materials Characterization, 59, 1728-1735.

[202]   Zhou, Z., Buchanan, F., Mitchell, C. and Dunne, N. (2014) Printability of Calcium Phosphate: Calcium Sulfate Powders for the Application of Tissue Engineered Bone Scaffolds Using the 3D Printing Technique. Materials Science and Engineering: C, 38, 1-10.