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Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing

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Abstract

The field of tissue engineering continues to advance with the discovery of new biomaterials, growth factors and scaffold fabrication techniques. However, for the ultimate success of a tissue engineered construct the issue of nutrient transport to the scaffold interior needs to be addressed. Often, the requirements for adequate nutrient supply are at odds with other scaffold design parameters such as mechanical properties as well as scaffold fabrication techniques, leading to incongruities in finding optimal solutions. The goal of this review article is to provide an overview of the various engineering design factors that promote movement of nutrients, waste and other biomolecules in scaffolds for musculoskeletal tissue engineering applications. The importance of diffusion in scaffolds and how it is influenced by porosity, permeability, architecture, and nutrient mixing has been emphasized. Methods for measuring porosity and permeability have also been outlined. The different types of biomaterials used, scaffold fabrication techniques implemented and the pore sizes/porosities obtained over the past 5 years have also been addressed.

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References

  1. Agrawal, C. M., J. S. McKinney, D. Huang., and K. A. Athanasiou. The use of the vibrating particle technique to fabricate highly porous and permeable biodegradable scaffolds. In: Synthetic Bioabsorbable Polymers for Implants, ASTM STP 1396, edited by C. M. Agrawal, J. E. Parr, and S. T. Lin. West Conshohocken, PA: American Society for Testing and Materials, 2000, pp. 99–114.

    Google Scholar 

  2. Agrawal, C. M., J. S. McKinney, D. Lanctot., and K. A. Athanasiou. Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering. Biomaterials 21(23):2443–2452, 2000.

    Google Scholar 

  3. Agrawal, C. M., and J. L. Ong. Personal Communication.

  4. Agrawal, C. M., and R. B. Ray. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. J. Biomed. Mater. Res. 55(2):141–150, 2001.

    Google Scholar 

  5. Ang, T. H., F. S. A. Sultana, D. W. Hutmacher, Y. S. Wong, J. Y. H. Fuh, X. M. Mo, H. T. Loh, E. Burdet., and S. H. Teoh. Fabrication of 3D chitosan-hydroxyapatite scafolds using a robotic dispensing system. Mater. Sci. Eng. C 20(1/2):35–42, 2002.

    Google Scholar 

  6. Athanasiou, K. A., J. P. Schmitz, and C. M. Agrawal. The effects of porosity on degradation of PLA-PGA implants. Tissue Eng. 4:53–63, 1998.

    Google Scholar 

  7. Bancroft, G. N., V. I. Sikavitsas, and A. G. Mikos. Design of a flow perfusion bioreactor system for bone tissue-engineering applications. Tissue Eng. 9(3):549–554, 2003.

    Google Scholar 

  8. Bancroft, G. N., V. I. Sikavitsas, J. Dolder., T. L. Sheffield, C. G. Ambrose, J. A. Jansen, and A. G. Mikos. Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc. Natl Acad. Sci. USA 99(20):12600–12605, 2002.

    Google Scholar 

  9. Barralet, J. E., L. Grover., T. Gaunt., A. J. Wright, and I. R. Gibson. Preparation of macroporous calcium phosphate cement tissue engineering scaffold. Biomaterials 23:3063–3072, 2002.

    Google Scholar 

  10. Bobyn, J. D., R. M. Pilliar, H. U. Cameron, and G. C. Weatherly. The optimum pore size for the fixation of porous-surfaced metal implants by the ingrowth of bone. Clin. Orthop. 150:263–270, 1980.

    Google Scholar 

  11. Bobyn, J. D., R. M. Pilliar, H. U. Cameron, G. C. Weatherly, and G. M. Kent. The effect of porous surface configuration on the tensile strength of fixation of implants by bone ingrowth. Clin. Orthop. 149:291–298, 1980.

    Google Scholar 

  12. Borden, M., S. F. El-Amin, M. Attawia., and C. T. Laurencin. Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair. Biomaterials 24:597–609, 2003.

    Google Scholar 

  13. Botchwey, E. A., M. A. Dupree, S. R. Pollack, E. M. Levine, and C. T. Laurencin. Tissue engineered bone: Measurement of nutrient transport in three-dimensional matrices. J. Biomed. Mater. Res. 67A:357–367, 2003.

    Google Scholar 

  14. Botchwey, E. A., S. R. Pollack, S. El-Amin, E. M. Levine, R. S. Tuan, and C. T. Laurencin. Human osteoblast-like cells in three-dimensional culture with fluid flow. Biorheology 40(1–3):299–306, 2003.

    Google Scholar 

  15. Burg, K. J. L., J. W. D. Holder, C. R. Culberson, R. J. Beiler, K. G. Greene, A. B. Loebsack, W. D. Roland, P. Eiselt., D. J. Mooney, and C. R. Halberstadt. Comparative study of seeding methods for three-dimensional polymeric scaffolds. J. Biomed. Mater. Res. 51:642–649, 2000.

    Google Scholar 

  16. Cao, T., K. H. Ho, and S. H. Teoh. Scaffold design and in vitro study of osteochondral coculture in a three-dimensional porous polycaprolactone scaffold fabricated by fused deposition modeling. Tissue Eng. 9 Supplement 1(4):S103–S112, 2003.

    Google Scholar 

  17. Carrier, R., M. Pupnick., R. Langer., L. Freed., and G. Vunjak-Novakovic. Effects of oxygen on engineered cardiac muscle. Biotechnol. Bioeng. 78:617–625, 2002.

    Google Scholar 

  18. Chu, T. M. G., D. G. Orton, S. J. Hollister, S. E. Feinberg, and J. W. Halloran. Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures. Biomaterials 23:1283–1293, 2002.

    Google Scholar 

  19. Cima, L. G., and M. J. Cima. Preparation of medical devices by solid free-form fabrication methods. United States Patent 5, 490, 962, 1996.

  20. Collins, R. E. Flow of Fluids Through Porous Material s. Tulsa., OK: PennWell Publishing Company, 1976, pp. 270.

    Google Scholar 

  21. Cooke, M. N., J. P. Fisher, D. Dean., C. Rimnac., and A. G. Mikos. Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth. J. Biomed. Mater. Res. 64B(2):65–69, 2003.

    Google Scholar 

  22. Crump, S. S. Apparatus and method for creating three-dimensional objects. United States Patent 5, 121, 329, 1992.

  23. Curodeau, A., E. Sachs., and S. Caldaraise. Design and fabrication of cast orthopedic implants with freeform surface textures from 3-D printed ceramic shell. J. Biomed. Mater. Res. 53:525–535, 2000.

    Google Scholar 

  24. Dolder, J., G. N. Bancroft, V. L. Sikavitsas, P. H. M. Spauwen, J. A. Jansen, and A. G. Mikos. Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh. J. Biomed. Mater. Res. 64A:235–241, 2003.

    Google Scholar 

  25. Eid, K., E. Chen., L. Griffith., and J. Glowacki. Effect of RGD coating on osteocompatibility of PLGA-polymer disks in a rat tibial wound. J. Biomed. Mater. Res. 57(2):224–231, 2001.

    Google Scholar 

  26. Fisher, J. P., J. W. Vehof, D. Dean., J. P. v. D. Waerden, T. A. Holland, A. G. Mikos, and J. A. Jansen. Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model. J. Biomed. Mater. Res. 59(3):547–556, 2002.

    Google Scholar 

  27. Freed, L. E., J. C. Marquis, G. Vunjak-Novakovic, J. Emmanual., and R. Langer. Composition of cell-polymer cartilage implants. Biotechnol. Bioeng. 43:605–614, 1994.

    Google Scholar 

  28. Freed, L. E., G. Vunjak-Novakovic, R. J. Biron, D. B. Eagles, D. C. Lesnoy, S. K. Barlow, and R. Langer. Biodegradable polymer scaffolds for tissue engineering. Biotechnology (NY) 12(7):689–693, 1994.

    Google Scholar 

  29. Freed, L. E., G. Vunjak-Novakovic, and R. Langer. Cultivation of cell-polymer cartilage implants in bioreactors. J. Cell. Biochem. 51(3):257–264, 1993.

    Google Scholar 

  30. Freed, L. E., G. Vunjak-Novakovic, J. C. Marquis, and R. Langer. Kinetics of chondrocyte growth in cell-polymer implants. Biotechnol. Bioeng. 43:597–604, 1994.

    Google Scholar 

  31. Giordano, R. A., B. M. Wu, S. W. Borland, L. G. Cima, E. M. Sachs, and M. J. Cima. Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing. J. Biomater. Sci. Polym. Ed. 8(1):63–75, 1996.

    Google Scholar 

  32. Goldstein, A. S., T. M. Juarez, C. D. Hemke, M. C. Gustin, and A. G. Mikos. Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffolds. Biomaterials 22:1279–1288, 2001.

    Google Scholar 

  33. Goldstein, A. S., G. Zhu., G. E. Morris, R. K. Meszlenyi, and A. G. Mikos. Effect of osteoblastic culture conditions on the structure of poly(DL-Lactic-co-Glycolic Acid) foam scaffolds. Tissue Eng. 5(5):421–433, 1999.

    Google Scholar 

  34. Gomes, M. E., V. I. Sikavitsas, E. Behravesh., R. L. Reis, and A. G. Mikos. Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three-dimensional scaffolds. J. Biomed. Mater. Res. 67A:87–95, 2003.

    Google Scholar 

  35. Gooch, K., J. Kwon., T. Blunk., R. Langer., L. E. Freed, and G. Vunjak-Novakovic. Effects of mixing intensity on tissue-engineered cartilage. Biotechnol. Bioeng. 72:402–407, 2001.

    Google Scholar 

  36. Grynpas, M. D., R. M. Pilliar, R. A. Kandel, R. Renlund., M. Filiaggi., and M. Dumitriu. Porous calcium polyphosphate scaffolds for bone substitute applications in vivo studies. Biomaterials 23:2063–2070, 2002.

    Google Scholar 

  37. Holy, C. E., J. A. Fialkov, J. E. Davies, and M. S. Shoichet. Use of a biomimetic strategy to engineer bone. J. Biomed. Mater. Res. 65A:447–453, 2003.

    Google Scholar 

  38. Hou, Q., D. W. Grijpma, and J. Feijen. Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials 24:1937–1947, 2003.

    Google Scholar 

  39. Hu, Y., D. W. Grainger, S. R. Winn, and J. O. Hollinger. Fabrication of poly(α-hydroxy acid) foam scaffolds using multiple solvent systems. J. Biomed. Mater. Res. 59:563–572, 2002.

    Google Scholar 

  40. Hull, C. W. Method for production of three-dimensional objects by stereolithography. United States Patent 4,929,402, 1990.

  41. Hutmacher, D. W., T. Schantz., I. Zein., K. W. Ng, S. H. Teoh, and K. C. Tan. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J. Biomed. Mater. Res. 55(2):203–216, 2001.

    Google Scholar 

  42. Hutmacher, D. W., S. H. Teoh, I. Zein., K. W. Ng, J. T. Schantz, and J. C. Leahy. Design and fabrication of a 3D scaffold for tissue engineering bone. In: Synthetic Bioabsorbable Polymers for Implants, ASTM STP 1396, edited by C. M. Agrawal, J. E. Parr, and S. T. Lin. West Conchohoden, PA: American Society for Testing and Materials, 2000, pp. 152–167.

    Google Scholar 

  43. Ishaug-Riley, S. Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds. J. Biomed. Mater. Res. 36(1):17–28, 1997.

    Google Scholar 

  44. Ishaug-Riley, S., G. M. Crane-Kruger, M. J. Yaszemski, and A. G. Mikos. Three-dimensional culture of rat calvarial osteoblasts in porous biodegradable polymers. Biomaterials 19(15):1405–1412, 1998.

    Google Scholar 

  45. Itälä, A., H. O. Ylänen, C. Ekholm., K. H. Karisson, and H. T. Aro. Pore diameter of more than 100 μm is not requisite for bone ingrowth in rabbits. J. Biomed. Mater. Res. 58:679–683, 2001.

    Google Scholar 

  46. Kim, B. S., and D. J. Mooney. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 16(5):224–230, 1998.

    Google Scholar 

  47. Kuboki, Y., Q. Jin., and H. Takita. Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis. J. Bone Joint Surg. 83-A(Supplement 1, Part 2):S1–105 to S1–115, 2001.

  48. LeBaron, R. G., and K. A. Athanasiou. Ex vivo synthesis of articular cartilage. Biomaterials 21:2575–2587, 2000.

    Google Scholar 

  49. Lee, Y. M., Y. J. Seol, Y. T. Lim, S. Kim., S. B. Han, I. C. Rhyu, S. H. Baek, S. J. Heo, J. Y. Choi, P. R. Klokkevold, and C. P. Chung. Tissue-engineered growth of bone by marrow cell transplantation using porous calcium metaphosphate matrices. J. Biomed. Mater. Res. 54:216–223, 2001.

    Google Scholar 

  50. Levy, R. A., T. M. G. Chu, J. W. Halloran, S. E. Feinberg, and S. Hollister. CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant. AJNR Am. J. Neuroradiol. 18(8):1522–1525, 1997.

    Google Scholar 

  51. Li, S., J. R. De Wijn, J. Li., P. Layrolle., and K. De Groot. Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio. Tissue Eng. 9(3):535–548, 2003.

    Google Scholar 

  52. Li, S. H., J. R. De Wijn, P. Layrolle., and K. De Groot. Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering. J. Biomed. Mater. Res. 61:109–120, 2002.

    Google Scholar 

  53. Li, W. J., C. T. Laurencin, E. J. Caterson, R. S. Tuan, and F. K. Ko. Electrospun nanofibrous structure: A novel scaffold for tissue engineering. J. Biomed. Mater. Res. 60(4):613–621, 2002.

    Google Scholar 

  54. Li, W. J., K. G. Danielson, P. G. Alexander, and R. S. Tuan. Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds. J. Biomed. Mater. Res. 67A(4):1105–1114, 2003.

    Google Scholar 

  55. Liao, C. J., C. F. Chen, J. H. Chen, S. F. Chiang, Y. J. Lin, and K. Y. Chang. Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method. J. Biomed. Mater. Res. 59:676–681, 2002.

    Google Scholar 

  56. Lin, A. S. P., T. H. Barrows, S. H. Cartmell, and R. E. Guldberg. Microarchitectural and mechanical characterization of oriented porous polymer scaffolds. Biomaterials 24:481–489, 2003.

    Google Scholar 

  57. Lu, S., W. F. Ramirez, and K. S. Anseth. Modeling and optimization of drug release from laminated polymer matrix devices. AIChE J. 44(7):1689–1696, 1998.

    Google Scholar 

  58. Ma, P. X., and J. W. Choi. Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. Tissue Eng. 7(1):23–33, 2001.

    Google Scholar 

  59. Ma, P. X., and R. Zhang. Microtubular architecture of biodegradable polymer scaffolds. J. Biomed. Mater. Res. 56:469–477, 2001.

    Google Scholar 

  60. Ma, P. X., and R. Zhang. Synthetic nano-scale fibrous extracellular matrix. J. Biomed. Mater. Res. 46(1):60–72, 1999.

    Google Scholar 

  61. Malaviya, P., and R. M. Nerem. Fluid-induced shear stress stimulates chondrocyte proliferation partially mediated via TGF-B1. Tissue Eng. 8(4):581–590, 2002.

    Google Scholar 

  62. Malda, J., J. Rouwkema., D. E. Martens, E. P. l. Comte, F. K. Kooy, J. Tramper., C. A. v. Blitterswijk, and J. Riesle. Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: Measurement and modeling. Biotechnol. Bioeng. 86(1):9–18, 2004.

    Google Scholar 

  63. Mankani, M. H., S. A. Kuznetsov, B. Fowler., A. Kingman., and P. G. Robey. In vivo bone formation by human bone marrow stromal cells: Effect of carrier particle size and shape. Biotechnol. Bioeng. 72:96–107, 2001.

    Google Scholar 

  64. Maquet, V., S. Blacher., R. Pirard., J. P. Pirard, M. N. Vyakarnam, and R. Jerome. Preparation of macroporous biodegradable poly(L-lactide-co-ε-caprolactone) foams and characterization by mercury intrusion porosimetry, image analysis, and impedance spectroscopy. J. Biomed. Mater. Res. 66A:199–213, 2003.

    Google Scholar 

  65. Maspero, F. A., K. Ruffieux., B. Muller., and E. Wintermantel. Resorbable defect analog PLGA scaffolds using CO2 as solvent: Structural characterization. J. Biomed. Mater. Res. 62:89–98, 2002.

    Google Scholar 

  66. Matthews, J. A., G. E. Wnek, D. G. Simpson, and G. L. Bowlin. Electrospinning of collagen nanofibers. Biomacromolecules 3:232–238, 2002.

    Google Scholar 

  67. Mooney, D. J., K. McNamara., D. Hern., J. P. Vacanti, and R. Langer. Stablized polyglycolic acid fibre-based tubes for tissue engineering. Biomaterials 17(2):115–124, 1996.

    Google Scholar 

  68. Murphy, C. L., and A. Sambanis. Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes. Tissue Eng. 7(6):791–803, 2001.

    Google Scholar 

  69. Murphy, W. L., R. G. Dennis, J. L. Kileny, and D. J. Mooney. Salt fusion: An approach to improve pore interconnectivity within tissue engineering scaffolds. Tissue Eng. 8(1):43–52, 2002.

    Google Scholar 

  70. Nam, Y. S., and T. G. Park. Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. J. Biomed. Mater. Res. 47:8–17, 1999.

    Google Scholar 

  71. Naumann, A., J. Aigner., R. Staudenmaier., M. Seemann., R. Bruening, K. H. Englmeier, G. Kadegge., A. Pavesio., E. Kastenbauer., and A. Berghaus. Clinical aspects and strategy for biomaterial engineering of an auricle based on three-dimensional stereolithography. Eur. Arch. Otorhinolaryngol. 260(10):568–575, 2003.

    Google Scholar 

  72. Oh, S. H., S. G. Kang, E. S. Kim, S. H. Cho, and J. H. Lee. Fabrication and characterization of hydrophilic poly(lactic-co-glycolic acid)/poly(vinyl alcohol) blend cell scaffolds by melt-molding particulate-leaching method. Biomaterials 24:4011–4021, 2003.

    Google Scholar 

  73. Oliveira, J. F. D., P. F. De Aguiar, A. M. Rossi, and G. A. Soares. Effect of process parameters on the characteristics of porous calcium phosphate ceramics for bone tissue scaffolds. Artif. Organs 27(5):406–411, 2003.

    Google Scholar 

  74. Park, A., B. Wu., and L. G. Griffith. Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion. J. Biomater. Sci. Polym. Ed. 9(2):89–110, 1998.

    Google Scholar 

  75. Peter, S. J., M. J. Miller, A. W. Yasko, M. J. Yaszemski, and A. G. Mikos. Polymer concepts in tissue engineering. J. Biomed. Mater. Res. 43(4):422–427, 1998.

    Google Scholar 

  76. Petrov, N., and S. R. Pollack. Comparative analysis of diffusive and stress induced nutrient transport efficiency in the lacunar-canalicular system of osteons. Biorheology 40(1–3):347–353, 2003.

    Google Scholar 

  77. Pilliar, R. M., M. Filiaggi., J. D. Wells, M. D. Grynpas, and R. A. Kandel. Porous calcium polyphosphate scaffolds for bone substitute applications-in vitro characterization. Biomaterials 22:963–972, 2001.

    Google Scholar 

  78. Porter, N. L., R. M. Pilliar, and M. D. Grynpas. Fabrication of porous calcium polyphosphate implants by solid freeform fabrication: A study of processing parameters and in vitro degradation characteristics. J. Biomed. Mater. Res. 56(4):504–515, 2001.

    Google Scholar 

  79. Ramay, H. R., and M. Zhang. Preparation of porous hydroxyapatite scaffolds by combination of the gel-casting and polymer sponge methods. Biomaterials 24:3293–3302, 2003.

    Google Scholar 

  80. Ramay, H. R. R., and M. Zhang. Biphasic calcium phosphate nanocomposite porous scaffolds for load-bearing bone tissue engineering. Biomaterials 25(21):5171–5180, 2004.

    Google Scholar 

  81. Reneker, D. H., and I. Chun. Nanometre diameter fibres of polymer, produced by electrospinning. Nanotechnology 7:216–223, 1996.

    Google Scholar 

  82. Rimell, J. T., and P. M. Marquis. Selective laser sintering of ultra high molecular weight polyethylene for clinical applications. J. Biomed. Mater. Res. 53(4):414–420, 2000.

    Google Scholar 

  83. Rodriguez-Lorenzo, L. M., M. Vallet-Regi, and J. M. F. Ferreira. Fabrication of porous hydroxyapatite bodies by a new direct consolidation method: Starch consolidation. J. Biomed. Mater. Res. 60:232–240, 2002.

    Google Scholar 

  84. Rodriguez-Lorenzo, L. M., M. Vallet-Regi, J. M. F. Ferreira, M. P. Ginebra, C. Aparicio., and J. A. Planell. Hydroxyapatite ceramic bodies with tailored mechanical properties for different applications. J. Biomed. Mater. Res. 60:159–166, 2002.

    Google Scholar 

  85. Rohner, D., D. W. Hutmacher, T. K. Cheng, M. Oberholzer., and B. Hammer. In vivo efficacy of bone-marrow-coated polycaprolactone scaffolds for the reconstruction of orbital defects in the pig. J. Biomed. Mater. Res. 66B(2):574–580, 2003.

    Google Scholar 

  86. Roy, T. D., J. L. Simon, J. L. Ricci, E. D. Rekow, V. P. Thompson, and J. R. Parsons. Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. J. Biomed. Mater. Res. 66A:283–291, 2003.

    Google Scholar 

  87. Roy, T. D., J. L. Simon, J. L. Ricci, E. D. Rekow, V. P. Thompson, and J. R. Parsons. Performance of hydroxyapatite bone repair scaffolds created via three-dimensional fabrication techniques. J. Biomed. Mater. Res. 67A:1228–1237, 2003.

    Google Scholar 

  88. Sachlos, E., and J. T. Czernuska. Making tissue engineering scaffolds work. Review on the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. Eur. Cell. Mater. 5:29–40, 2003.

    Google Scholar 

  89. Sachs, E., A. Curodeau., T. Fan., J. F. Bredt, M. Cima., and D. Brancazio. Three dimensional printing system. United States Patent 5,807,437, 1998.

  90. Saini, S., and T. M. Wick. Concentric cylinder bioreactor for production of tissue engineered cartilage: Effect of seeding density and hydrodynamic loading on construct development. Biotechnol. Prog. 19(2):510–521, 2003.

    Google Scholar 

  91. Scheidegger, A. E. The Physics of Flow Through Porous Media. New York: Macmillan, 1957, pp. 236.

    Google Scholar 

  92. Sheridan, M. H., L. D. Shea, M. C. Peters, and D. J. Mooney. Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J. Control. Release 64:91–102, 2000.

    Google Scholar 

  93. Sherwood, J. K., S. L. Riley, R. Palazzolo., S. C. Brown, D. C. Monkhouse, M. Coates., L. G. Griffith, L. K. Landeen, and A. Ratcliffe. A three-dimensional osteochondral composite scaffold for articular cartilage repair. Biomaterials 23:4739–4751, 2002.

    Google Scholar 

  94. Shishkovsky, I. V., E. Y. Tarasova, L. V. huravel, and A. L. Petrov. The synthesis of a biocomposite based on nickel titanium and hydroxyapatite under selective laser sintering conditions. Tech. Phys. Lett. 27(3):211–213, 2001.

    Google Scholar 

  95. Sikavitsas, V. I., G. N. Bancroft, and A. G. Mikos. Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. J. Biomed. Mater. Res. 62:136–148, 2002.

    Google Scholar 

  96. Sikavitsas, V. I., G. N. Bancroft, H. L. Holtorf, J. A. Jansen, and A. G. Mikos. Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Proc. Natl Acad. Sci. USA 100(25):14683–14688, 2003.

    Google Scholar 

  97. Simon, J. L., T. D. Roy, J. R. Parsons, E. D. Rekow, V. P. Thompson, J. Kemnitzer., and J. L. Ricci. Engineered cellular response to scaffold architecture in a rabbit trephine defect. J. Biomed. Mater. Res. 66A(2):275–282, 2003.

    Google Scholar 

  98. Singhal, A. R., C. M. Agrawal, and K. A. Athanasiou. Salient degradation features of a 50:50 PLA/PGA scaffold for tissue engineering. Tissue Eng. 2(3):197–207, 1996.

    Google Scholar 

  99. Sittinger, M., C. Perka., O. Schultz., T. Haupl., and G. R. Burmester. Joint cartilage regeneration by tissue engineering. Z Rheumatol. 58(3):130–135, 1999.

    Google Scholar 

  100. Sodian, R., M. Loebe., A. Hein., D. P. Martin, S. P. Hoerstrup, E. V. Potapov, H. Hausmann., T. Lueth., and R. Hetzer. Application of stereolithography for scaffold fabrication for tissue engineered heart valves. ASAIO J. 48(1):12–16, 2002.

    Google Scholar 

  101. Spaans, C. J., V. W. Belgraver, O. Rienstra., J. H. de Groot, R. P. H. Veth, and A. J. Pennings. Solvent-free fabrication of micro-porous polyurethane amide and polyurethane-urea scaffolds for repair and replacement of the knee-joint meniscus. Biomaterials 21:2453–2460, 2000.

    Google Scholar 

  102. Suh, S. W., J. Y. Shin, J. Kim., J. Kim., C. H. Beak, D. I. Kim, H. Kim., S. S. Jeon, and I.-W. Choo. Effect of different particles on cell proliferation in polymer scaffolds using a solvent-casting and particulate leaching technique. ASAIO J. 48:460–464, 2002.

    Google Scholar 

  103. Taboas, J. M., R. D. Maddox, P. H. Krebsbach, and S. J. Hollister. Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer–ceramic scaffolds. Biomaterials 24:181–194, 2003.

    Google Scholar 

  104. Tan, K. H., C. K. Chua, K. F. Leong, C. M. Cheah, P. Cheang., M. S. A. Bakar, and S. W. Cha. Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends. Biomaterials 24(18):3115–3123, 2003.

    Google Scholar 

  105. Thomson, R. C., M. J. Yaszemski, J. M. Powers, and A. G. Mikos. Hydroxyapatite fiber reinforced poly(α-hydroxy ester) foams for bone regeneration. Biomaterials 19:1935–1943, 1998.

    Google Scholar 

  106. Tienen, T. v., R. Heijkants., P. Buma., J. de Groot, A. Pennings., and R. Verth. Tissue ingrowth and degradation of two biodegradable porous polymers with different porosities and pore sizes. Biomaterials 23(8):1731–1738, 2002.

    Google Scholar 

  107. Vacanti, J. P. Beyond Transplantation. Third Annual Samuel Jason Mixter Lecture. Arch. Surg. 123(5):545–549, 1988.

    Google Scholar 

  108. Vacanti, J. P., M. A. Morse, W. M. Saltzman, A. J. Domb, A. Perez-Atayde, R. Langer., C. L. Mazzoni, and C. Breuer. Selective cell transplantation using bioabsorbable artificial polymers as matrices. J. Pediatr. Surg. 23:3–9, 1988.

    Google Scholar 

  109. Vehof, J. W. M., J. P. Fisher, D. Dean., J. P. C. M. Van der Waerden, P. H. M. Spauwen, A. G. Mikos, and J. A. Jansen. Bone formation in transforming growth factor β-1-coated porous poly(propylene fumarate) scaffolds. J. Biomed. Mater. Res. 60:241–251, 2002.

    Google Scholar 

  110. Vunjak-Novakovic, G., L. E. Freed, R. Biron., and R. Langer. Effects of mixing on the composition and morphology of tissue-engineered cartilage. AIChE J. 42(3):850–860, 1996.

    Google Scholar 

  111. Vunjak-Novakovic, G., I. Martin., B. Obradovic., S. Treppo., A. J. Grodzinsky, R. Langer., and L. E. Freed. Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineering cartilage. J. Orthop. Res. 17(1):130–138, 1999.

    Google Scholar 

  112. Vunjak-Novakovic, G., B. Obradovic., I. Martin., P. M. Bursac, R. Langer., and L. E. Freed. Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering. Biotechnol. Prog. 14(2):193–202, 1998.

    Google Scholar 

  113. Whang, K., T. K. Goldstick, and K. E. Healy. A biodegradable polymer scaffold for delivery of osteotropic factors. Biomaterials 21:2545–2551, 2000.

    Google Scholar 

  114. Whang, K., K. E. Healy, D. R. Elenz, E. K. Nam, D. C. Tsai, C. H. Thomas, G. W. Nuber, F. H. Glorieux, R. Travers., and S. M. Sprague. Engineering bone regeneration with bioabsorable scaffolds with novel architecture. Tissue Eng. 5(1):35–51, 1999.

    Google Scholar 

  115. Widmer, M. S., P. K. Gupta, L. Lu., R. K. Meszlenyi, G. R. D. Evans, K. Brandt., T. Savel., A. Gurlek Jr., C. W. P., and A. G. Mikos. Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration. Biomaterials 19:1945–1955, 1998.

  116. Wintermantel, E., J. Mayer., J. Blum., K. L. Eckert, P. Luscher., and M. Mathey. Tissue engineering scaffolds using superstructures. Biomaterials 17:83–91, 1996.

    Google Scholar 

  117. Wu, B. M., S. W. Borland, R. A. Giordano, L. G. Cima, E. M. Sachs, and M. J. Cima. Solid free-form fabrication of drug delivery devices. J. Control. Release 40(1–2):77–87, 1996.

    Google Scholar 

  118. Yang, J., G. Shi., J. Bei., S. Wang., Y. Cao., Q. Shang., G. Yang., and W. Wang. Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast cell culture. J. Biomed. Mater. Res. 62:438–446, 2002.

    Google Scholar 

  119. Yang, S., K. F. Leong, Z. Du., and C. K. Chua. The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue Eng. 8(1):1–11, 2002.

    Google Scholar 

  120. Yang, S., K. F. Leong, Z. Du., and C. K. Chua. The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue Eng. 7(6):679–689, 2001.

    Google Scholar 

  121. Yoon, J. J., and T. G. Park. Degradation behaviors of biodegradable macroporous scaffolds prepared by gas foaming of effervescent salts. J. Biomed. Mater. Res. 55:401–408, 2001.

    Google Scholar 

  122. Yoshimoto, H., Y. M. Shin, H. Terai., and J. P. Vacanti. A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 24(12):2077–2082, 2003.

    Google Scholar 

  123. Zein, I., D. W. Hutmacher, K. C. Tan, and S. H. Teoh. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials 23:1169–1185, 2002.

    Google Scholar 

  124. Zeltinger, J., J. K. Sherwood, D. A. Graham, R. Mueller., and L. G. Griffith. Effect of pore size and void fraction on cellular adhesion proliferation, and matrix deposition. Tissue Eng. 7(5):557–572, 2001.

    Google Scholar 

  125. Zhang, R., and P. X. Ma. Poly(α-hydroxyl acids)/hydroxyapatite porous composites for bone-tissue engineering. I. Preparation and morphology. J. Biomed. Mater. Res. 44(4):446–455, 1999.

    Google Scholar 

  126. Zhao, F., Y. Yin., W. W. Lu, J. C. Leong, W. Zhang., J. Zhang., M. Zhang., and K. Yao. Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chtosan-gelatin network composite scaffolds. Biomaterials 23:3227–3234, 2002.

    Google Scholar 

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Correspondence to C. Mauli Agrawal.

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Karande, T.S., Ong, J.L. & Agrawal, C.M. Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing. Ann Biomed Eng 32, 1728–1743 (2004). https://doi.org/10.1007/s10439-004-7825-2

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