Skip to main content

Advertisement

Log in

A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abarrategi, A., M. E. Fernandez-Valle, T. Desmet, D. Castejon, A. Civantos, C. Moreno-Vicente, V. Ramos, J. V. Sanz-Casado, F. J. Martinez-Vazquez, P. Dubruel, P. Miranda, and J. L. Lopez-Lacomba. Label-free magnetic resonance imaging to locate live cells in three-dimensional porous scaffolds. J. R. Soc. Interface R. Soc. 9:2321–2331, 2012.

    CAS  Google Scholar 

  2. Anthanasiou, K. A., E. M. Darling, and J. C. Hu. Articular Cartilage Tissue Engineering. San Rafael: Morgan and Claypool Publishers, 2010.

    Google Scholar 

  3. Arenas-Herrera, J. E., I. K. Ko, A. Atala, and J. J. Yoo. Decellularization for whole organ bioengineering. Biomed. Mater. 8:014106, 2013.

    CAS  PubMed  Google Scholar 

  4. Atala, A., S. B. Bauer, S. Soker, J. J. Yoo, and A. B. Retik. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246, 2006.

    PubMed  Google Scholar 

  5. Badylak, S. F. The extracellular matrix as a biologic scaffold material. Biomaterials 28:3587–3593, 2007.

    CAS  PubMed  Google Scholar 

  6. Badylak, S. F., and T. W. Gilbert. Immune response to biologic scaffold materials. Semin. Immunol. 20:109–116, 2008.

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Bago, J. R., E. Aguilar, M. Alieva, C. Soler-Botija, O. F. Vila, S. Claros, J. A. Andrades, J. Becerra, N. Rubio, and J. Blanco. In vivo bioluminescence imaging of cell differentiation in biomaterials: a platform for scaffold development. Tissue Eng. Part A 19:593–603, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Bell, E., H. P. Ehrlich, D. J. Buttle, and T. Nakatsuji. Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. Science 211:1052–1054, 1981.

    CAS  PubMed  Google Scholar 

  9. Bello, Y. M., A. F. Falabella, and W. H. Eaglstein. Tissue-engineered skin. Current status in wound healing. Am. J. Clin. Dermatol. 2:305–313, 2001.

    CAS  PubMed  Google Scholar 

  10. Benton, J. A., B. D. Fairbanks, and K. S. Anseth. Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable peg hydrogels. Biomaterials 30:6593–6603, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Bosman, F. T., and I. Stamenkovic. Functional structure and composition of the extracellular matrix. J. Pathol. 200:423–428, 2003.

    CAS  PubMed  Google Scholar 

  12. Burg, K. J., S. Porter, and J. F. Kellam. Biomaterial developments for bone tissue engineering. Biomaterials 21:2347–2359, 2000.

    CAS  PubMed  Google Scholar 

  13. Burke, J. F., I. V. Yannas, W. C. Quinby, Jr, C. C. Bondoc, and W. K. Jung. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann. Surg. 194:413–428, 1981.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Caplan, A. I., and J. E. Dennis. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 98:1076–1084, 2006.

    CAS  PubMed  Google Scholar 

  15. Chan, B. P., and K. W. Leong. Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur. Spine J. 17(Suppl 4):467–479, 2008.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Chertok, B., M. J. Webber, M. D. Succi, and R. Langer. Drug delivery interfaces in the 21st century: from science fiction ideas to viable technologies. Mol. Pharm. 10:3531–3543, 2013.

    CAS  PubMed  Google Scholar 

  17. Cui, X., and T. Boland. Human microvasculature fabrication using thermal inkjet printing technology. Biomaterials 30:6221–6227, 2009.

    CAS  PubMed  Google Scholar 

  18. Daly, K. A., S. Liu, V. Agrawal, B. N. Brown, A. Huber, S. A. Johnson, J. Reing, B. Sicari, M. Wolf, X. Zhang, and S. F. Badylak. The host response to endotoxin-contaminated dermal matrix. Tissue Eng. Part A 18:1293–1303, 2012.

    CAS  PubMed  Google Scholar 

  19. Dang, T. T., A. V. Thai, J. Cohen, J. E. Slosberg, K. Siniakowicz, J. C. Doloff, M. Ma, J. Hollister-Lock, K. M. Tang, Z. Gu, H. Cheng, G. C. Weir, R. Langer, and D. G. Anderson. Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug. Biomaterials 34:5792–5801, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Davis, G. E., K. J. Bayless, M. J. Davis, and G. A. Meininger. Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules. Am. J. Pathol. 156:1489–1498, 2000.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Derby, B. Printing and prototyping of tissues and scaffolds. Science 338:921–926, 2012.

    CAS  PubMed  Google Scholar 

  22. di Summa, P. G., P. J. Kingham, C. C. Campisi, W. Raffoul, and D. F. Kalbermatten. Collagen (neuragen((r))) nerve conduits and stem cells for peripheral nerve gap repair. Neurosci. Lett. 572:26–31, 2014.

    PubMed  Google Scholar 

  23. Diederichs, S., K. Baral, M. Tanner, and W. Richter. Interplay between local versus soluble transforming growth factor-beta and fibrin scaffolds: role of cells and impact on human mesenchymal stem cell chondrogenesis. Tissue Eng. Part A 18:1140–1150, 2012.

    CAS  PubMed  Google Scholar 

  24. Elliott, R. B., L. Escobar, R. Calafiore, G. Basta, O. Garkavenko, A. Vasconcellos, and C. Bambra. Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys. Transplant. Proc. 37:466–469, 2005.

    CAS  PubMed  Google Scholar 

  25. Falanga, V., and M. Sabolinski. A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen. 7:201–207, 1999.

    CAS  PubMed  Google Scholar 

  26. Fishman, J. M., M. W. Lowdell, L. Urbani, T. Ansari, A. J. Burns, M. Turmaine, J. North, P. Sibbons, A. M. Seifalian, K. J. Wood, M. A. Birchall, and P. De Coppi. Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model. Proc. Natl. Acad. Sci. USA 110:14360–14365, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Folkman, J. H., and M. Hochberg. Self regulation of growth in three dimensions. J. Exp. Med. 138:745–753, 1973.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Foster, L. J., and E. Karsten. A chitosan based, laser activated thin film surgical adhesive, ‘SurgiLux’: preparation and demonstration. J. Vis. Exp JoVE 68:xv–xvii, 2012.

    Google Scholar 

  29. Frisch, S. M., and H. Francis. Disruption of epithelial cell-matrix interactions induces apoptosis. J. Cell Biol. 124:619–626, 1994.

    CAS  PubMed  Google Scholar 

  30. Gabella, G. Structure of smooth muscles. In: Handbook of Experimental Pharmacology, Vol. 111, edited by L. Szekeres, and J. G. Y. Papp. Berlin: Springer, 1994, pp. 3–34.

    Google Scholar 

  31. Geerligs, M., L. van Breemen, G. Peters, P. Ackermans, F. Baaijens, and C. Oomens. In vitro indentation to determine the mechanical properties of epidermis. J. Biomech. 44:1176–1181, 2011.

    PubMed  Google Scholar 

  32. Geller, H. M., and J. W. Fawcett. Building a bridge: Engineering spinal cord repair. Exp. Neurol. 174:125–136, 2002.

    PubMed  Google Scholar 

  33. Ghanaati, S., M. J. Webber, R. E. Unger, C. Orth, J. F. Hulvat, S. E. Kiehna, M. Barbeck, A. Rasic, S. I. Stupp, and C. J. Kirkpatrick. Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers. Biomaterials 30:6202–6212, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Ghanaati, S., S. Fuchs, M. J. Webber, C. Orth, M. Barbeck, M. E. Gomes, R. L. Reis, and C. J. Kirkpatrick. Rapid vascularization of starch-poly(caprolactone) in vivo by outgrowth endothelial cells in co-culture with primary osteoblasts. J. Tissue Eng. Regen. Med. 5:e136–e143, 2011.

    CAS  PubMed  Google Scholar 

  35. Ghanaati, S., R. E. Unger, M. J. Webber, M. Barbeck, C. Orth, J. A. Kirkpatrick, P. Booms, A. Motta, C. Migliaresi, R. A. Sader, and C. J. Kirkpatrick. Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells. Biomaterials 32:8150–8160, 2011.

    CAS  PubMed  Google Scholar 

  36. Giano, M. C., D. J. Pochan, and J. P. Schneider. Controlled biodegradation of self-assembling beta-hairpin peptide hydrogels by proteolysis with matrix metalloproteinase-13. Biomaterials 32:6471–6477, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Green, H., O. Kehinde, and J. Thomas. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc. Natl. Acad. Sci. USA 76:5665–5668, 1979.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Guo, Y., T. Yuan, Z. Xiao, P. Tang, Y. Xiao, Y. Fan, and X. Zhang. Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer network for cartilage tissue engineering. J. Mater. Sci. Mater. Med. 23:2267–2279, 2012.

    CAS  PubMed  Google Scholar 

  39. Guvendiren, M., and J. A. Burdick. Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat. Commun. 3:792, 2012.

    PubMed  Google Scholar 

  40. Heeschen, C., R. Lehmann, J. Honold, B. Assmus, A. Aicher, D. H. Walter, H. Martin, A. M. Zeiher, and S. Dimmeler. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 109:1615–1622, 2004.

    PubMed  Google Scholar 

  41. Herring, G. M. The chemical structure of tendon, cartilage, dentin and bone matrix. Clin. Orthop. Relat. Res. 60:261–299, 1968.

    CAS  PubMed  Google Scholar 

  42. Hillel, A. T., S. Unterman, Z. Nahas, B. Reid, J. M. Coburn, J. Axelman, J. J. Chae, Q. Guo, R. Trow, A. Thomas, Z. Hou, S. Lichtsteiner, D. Sutton, C. Matheson, P. Walker, N. David, S. Mori, J. M. Taube, and J. H. Elisseeff. Photoactivated composite biomaterial for soft tissue restoration in rodents and in humans. Sci. Transl. Med. 3:93ra67, 2011.

    CAS  PubMed  Google Scholar 

  43. Holmes, C., M. Tabrizian, and P. O. Bagnaninchi. Motility imaging via optical coherence phase microscopy enables label-free monitoring of tissue growth and viability in 3D tissue-engineering scaffolds. J. Tissue Eng. Regen. Med. 2013. doi:10.1002/term.1687.

  44. Holmes, C., J. Daoud, P. O. Bagnaninchi, and M. Tabrizian. Polyelectrolyte multilayer coating of 3D scaffolds enhances tissue growth and gene delivery: non-invasive and label-free assessment. Adv. Healthc. Mater. 3:572–580, 2014.

    CAS  PubMed  Google Scholar 

  45. Hutmacher, D. W. Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543, 2000.

    CAS  PubMed  Google Scholar 

  46. Jaklenec, A., A. Stamp, E. Deweerd, A. Sherwin, and R. Langer. Progress in the tissue engineering and stem cell industry “are we there yet?”. Tissue Eng. Part B Rev. 18:155–166, 2012.

    PubMed  Google Scholar 

  47. Kadler, K. E., D. F. Holmes, J. A. Trotter, and J. A. Chapman. Collagen fibril formation. Biochem. J. 316:1–11, 1996.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Kanematsu, A., S. Yamamoto, M. Ozeki, T. Noguchi, I. Kanatani, O. Ogawa, and Y. Tabata. Collagenous matrices as release carriers of exogenous growth factors. Biomaterials 25:4513–4520, 2004.

    CAS  PubMed  Google Scholar 

  49. Katta, J., T. Stapleton, E. Ingham, Z. M. Jin, and J. Fisher. The effect of glycosaminoglycan depletion on the friction and deformation of articular cartilage. Proc. Inst. Mech. Eng. Part H 222:1–11, 2008.

    CAS  Google Scholar 

  50. Kazemi, M. and L. P. Li. A viscoelastic poromechanical model of the knee joint in large compression. Med. Eng. Phys. 36:998–1006, 2014.

  51. Keane, T. J., R. Londono, N. J. Turner, and S. F. Badylak. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials 33:1771–1781, 2012.

    CAS  PubMed  Google Scholar 

  52. Khan, O. F., and M. V. Sefton. Patterning collagen/poloxamine-methacrylate hydrogels for tissue-engineering-inspired microfluidic and laser lithography applications. J. Biomater. Sci. Polym. Ed. 22:2499–2514, 2011.

    CAS  Google Scholar 

  53. Khan, O. F., D. N. Voice, B. M. Leung, and M.V. Sefton. A novel high-speed production process to create modular components for the bottom-up assembly of large-scale tissue-engineered constructs. Adv. Healthc. Mater. 2014. doi:10.1002/adhm.201400150.

  54. Kim, K. D., and N. M. Wright. Polyethylene glycol hydrogel spinal sealant (duraseal spinal sealant) as an adjunct to sutured dural repair in the spine: results of a prospective, multicenter, randomized controlled study. Spine 36:1906–1912, 2011.

    PubMed  Google Scholar 

  55. Kim, A. M., C. M. Tingen, and T. K. Woodruff. Sex bias in trials and treatment must end. Nature 465:688–689, 2010.

    CAS  PubMed  Google Scholar 

  56. Langer, R. A personal account of translating discoveries in an academic lab. Nat. Biotechnol. 31:487–489, 2013.

    CAS  PubMed  Google Scholar 

  57. Langer, R., and J. P. Vacanti. Tissue engineering. Science. 260:920–926, 1993.

    CAS  PubMed  Google Scholar 

  58. Lee, H. S., S. W. Teng, H. C. Chen, W. Lo, Y. Sun, T. Y. Lin, L. L. Chiou, C. C. Jiang, and C. Y. Dong. Imaging human bone marrow stem cell morphogenesis in polyglycolic acid scaffold by multiphoton microscopy. Tissue Eng. 12:2835–2841, 2006.

    CAS  PubMed  Google Scholar 

  59. Lee, M. H., J. A. Arcidiacono, A. M. Bilek, J. J. Wille, C. A. Hamill, K. M. Wonnacott, M. A. Wells, and S. S. Oh. Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the united states. Tissue Eng. Part. B Rev. 16:41–54, 2010.

    CAS  PubMed  Google Scholar 

  60. Lee, J. E., S. Park, M. Park, M. H. Kim, C. G. Park, S. H. Lee, S. Y. Choi, B. H. Kim, H. J. Park, J. H. Park, C. Y. Heo, and Y. B. Choy. Surgical suture assembled with polymeric drug-delivery sheet for sustained, local pain relief. Acta Biomater. 9:8318–8327, 2013.

    CAS  PubMed  Google Scholar 

  61. L’Heureux, N., N. Dusserre, G. Konig, B. Victor, P. Keire, T. N. Wight, N. A. Chronos, A. E. Kyles, C. R. Gregory, G. Hoyt, R. C. Robbins, and T. N. McAllister. Human tissue-engineered blood vessels for adult arterial revascularization. Nat. Med. 12:361–365, 2006.

    PubMed Central  PubMed  Google Scholar 

  62. L’Heureux, N., T. N. McAllister, and L. M. de la Fuente. Tissue-engineered blood vessel for adult arterial revascularization. New Engl. J. Med. 357:1451–1453, 2007.

    PubMed  Google Scholar 

  63. Lieber, R. L., and S. C. Bodine-Fowler. Skeletal muscle mechanics: Implications for rehabilitation. Phys. Ther. 73:844–856, 1993.

    CAS  PubMed  Google Scholar 

  64. Linke, W. A., and N. Hamdani. Gigantic business: titin properties and function through thick and thin. Circ. Res. 114:1052–1068, 2014.

    CAS  PubMed  Google Scholar 

  65. Liu, J., J. Hilderink, T. A. Groothuis, C. Otto, C. A. van Blitterswijk, and J. de Boer. Monitoring nutrient transport in tissue-engineered grafts. J. Tissue Eng. Regen. Med. 2013.

  66. Lucero, H. A., and H. M. Kagan. Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell. Mol. Life Sci. 63:2304–2316, 2006.

    CAS  PubMed  Google Scholar 

  67. Macchiarini, P., P. Jungebluth, T. Go, M. A. Asnaghi, L. E. Rees, T. A. Cogan, A. Dodson, J. Martorell, S. Bellini, P. P. Parnigotto, S. C. Dickinson, A. P. Hollander, S. Mantero, M. T. Conconi, and M. A. Birchall. Clinical transplantation of a tissue-engineered airway. Lancet 372:2023–2030, 2008.

    PubMed  Google Scholar 

  68. Macdonald, M. L., R. E. Samuel, N. J. Shah, R. F. Padera, Y. M. Beben, and P. T. Hammond. Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants. Biomaterials 32:1446–1453, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. MacNeil, S. Progress and opportunities for tissue-engineered skin. Nature 445:874–880, 2007.

    CAS  PubMed  Google Scholar 

  70. Mangera, A., A. J. Bullock, S. Roman, C. R. Chapple, and S. MacNeil. Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair. BJU Int. 112:674–685, 2013.

    CAS  PubMed  Google Scholar 

  71. Marston, W. A., J. Hanft, P. Norwood, and R. Pollak. The efficacy and safety of dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. 26:1701–1705, 2003.

    PubMed  Google Scholar 

  72. Mathur, A. B., A. M. Collinsworth, W. M. Reichert, W. E. Kraus, and G. A. Truskey. Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy. J. Biomech. 34:1545–1553, 2001.

    CAS  PubMed  Google Scholar 

  73. Mestas, J., and C. C. Hughes. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172:2731–2738, 2004.

    CAS  PubMed  Google Scholar 

  74. Miller, J. S., K. R. Stevens, M. T. Yang, B. M. Baker, D. H. T. Nguyen, D. M. Cohen, E. Toro, A. A. Chen, P. A. Galie, X. Yu, R. Chaturvedi, S. N. Bhatia, and C. S. Chen. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11:768–774, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Morelli, A. E., and A. W. Thomson. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7:610–621, 2007.

    CAS  PubMed  Google Scholar 

  76. Nillesen, S. T., P. J. Geutjes, R. Wismans, J. Schalkwijk, W. F. Daamen, and T. H. van Kuppevelt. Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF-2 and VEGF. Biomaterials 28:1123–1131, 2007.

    CAS  PubMed  Google Scholar 

  77. Nishida, K. Tissue engineering of the cornea. Cornea 22:S28–S34, 2003.

    PubMed  Google Scholar 

  78. Odian, G. G. Principles of Polymerization. Hoboken, NJ: Wiley-Interscience, 2004.

    Google Scholar 

  79. Ommaya, A. K. Mechanical properties of tissues of the nervous system. J. Biomech. 1:127–138, 1968.

    CAS  PubMed  Google Scholar 

  80. Ott, H. C., T. S. Matthiesen, S. K. Goh, L. D. Black, S. M. Kren, T. I. Netoff, and D. A. Taylor. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14:213–221, 2008.

    CAS  PubMed  Google Scholar 

  81. Ott, H. C., B. Clippinger, C. Conrad, C. Schuetz, I. Pomerantseva, L. Ikonomou, D. Kotton, and J. P. Vacanti. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16:927–933, 2010.

    CAS  PubMed  Google Scholar 

  82. Oxlund, H., J. Manschot, and A. Viidik. The role of elastin in the mechanical properties of skin. J. Biomech. 21:213–218, 1988.

    CAS  PubMed  Google Scholar 

  83. Park, K. M., and H. M. Woo. Systemic decellularization for multi-organ scaffolds in rats. Transpl. Proc. 44:1151–1154, 2012.

    CAS  Google Scholar 

  84. Paul, S. M., D. S. Mytelka, C. T. Dunwiddie, C. C. Persinger, B. H. Munos, S. R. Lindborg, and A. L. Schacht. How to improve r&d productivity: The pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov. 9:203–214, 2010.

    CAS  PubMed  Google Scholar 

  85. Petersen, O. W., L. Ronnov-Jessen, A. R. Howlett, and M. J. Bissell. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc. Natl. Acad. Sci. USA 89:9064–9068, 1992.

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Place, E. S., J. H. George, C. K. Williams, and M. M. Stevens. Synthetic polymer scaffolds for tissue engineering. Chem. Soc. Rev. 38:1139–1151, 2009.

    CAS  PubMed  Google Scholar 

  87. Price, A. P., L. M. Godin, A. Domek, T. Cotter, J. D’Cunha, D. A. Taylor, and A. Panoskaltsis-Mortari. Automated decellularization of intact, human-sized lungs for tissue engineering. Tissue Eng. Part C. 2014.

  88. Restifo, N. P., F. M. Marincola, Y. Kawakami, J. Taubenberger, J. R. Yannelli, and S. A. Rosenberg. Loss of functional beta2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J. Natl. Cancer Inst. 88:100–108, 1996.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Rho, J.-Y., L. Kuhn-Spearing, and P. Zioupos. Mechanical properties and the hierarchical structure of bone. Med. Eng. Phys. 20:92–102, 1998.

    CAS  PubMed  Google Scholar 

  90. Saher, G., B. Brugger, C. Lappe-Siefke, W. Mobius, R. Tozawa, M. C. Wehr, F. Wieland, S. Ishibashi, and K. A. Nave. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci. 8:468–475, 2005.

    CAS  PubMed  Google Scholar 

  91. Salinas, C. N., and K. S. Anseth. The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities. Biomaterials 29:2370–2377, 2008.

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Salvatori, M., R. Katari, T. Patel, A. Peloso, J. Mugweru, K. Owusu, and G. Orlando. Extracellular matrix scaffold technology for bioartificial pancreas engineering: State of the art and future challenges. J. Diabetes Sci. Technol. 8:159–169, 2014.

    CAS  PubMed  Google Scholar 

  93. Seok, J., H. S. Warren, A. G. Cuenca, M. N. Mindrinos, H. V. Baker, W. Xu, D. R. Richards, G. P. McDonald-Smith, H. Gao, L. Hennessy, C. C. Finnerty, C. M. Lopez, S. Honari, E. E. Moore, J. P. Minei, J. Cuschieri, P. E. Bankey, J. L. Johnson, J. Sperry, A. B. Nathens, T. R. Billiar, M. A. West, M. G. Jeschke, M. B. Klein, R. L. Gamelli, N. S. Gibran, B. H. Brownstein, C. Miller-Graziano, S. E. Calvano, P. H. Mason, J. P. Cobb, L. G. Rahme, S. F. Lowry, R. V. Maier, L. L. Moldawer, D. N. Herndon, R. W. Davis, W. Xiao, and R. G. Tompkins. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl. Acad. Sci. USA 110:3507–3512, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  94. Shah, N. J., M. L. Macdonald, Y. M. Beben, R. F. Padera, R. E. Samuel, and P. T. Hammond. Tunable dual growth factor delivery from polyelectrolyte multilayer films. Biomaterials 32:6183–6193, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Shah, N. J., M. N. Hyder, J. S. Moskowitz, M. A. Quadir, S. W. Morton, H. J. Seeherman, R. F. Padera, M. Spector, and P. T. Hammond. Surface-mediated bone tissue morphogenesis from tunable nanolayered implant coatings. Sci. Transl. Med. 5:191ra183, 2013.

    Google Scholar 

  96. Sharma, B., S. Fermanian, M. Gibson, S. Unterman, D. A. Herzka, B. Cascio, J. Coburn, A. Y. Hui, N. Marcus, G. E. Gold, and J. H. Elisseeff. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci. Transl. Med. 5:167ra166, 2013.

    Google Scholar 

  97. Shen, Y. H., M. S. Shoichet, and M. Radisic. Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. Acta Biomater. 4:477–489, 2008.

    CAS  PubMed  Google Scholar 

  98. Shultz, L. D., F. Ishikawa, and D. L. Greiner. Humanized mice in translational biomedical research. Nat. Rev. Immunol. 7:118–130, 2007.

    CAS  PubMed  Google Scholar 

  99. Singh, A., Y. Lu, C. Chen, and J. M. Cavanaugh. Mechanical properties of spinal nerve roots subjected to tension at different strain rates. J. Biomech. 39:1669–1676, 2006.

    PubMed  Google Scholar 

  100. Song, J. J., J. P. Guyette, S. E. Gilpin, G. Gonzalez, J. P. Vacanti, and H. C. Ott. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19:646–651, 2013.

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Starzl, T. E., N. Murase, K. Abu-Elmagd, E. A. Gray, R. Shapiro, B. Eghtesad, R. J. Corry, M. L. Jordan, P. Fontes, T. Gayowski, G. Bond, V. P. Scantlebury, S. Potdar, P. Randhawa, T. Wu, A. Zeevi, M. A. Nalesnik, J. Woodward, A. Marcos, M. Trucco, A. J. Demetris, and J. J. Fung. Tolerogenic immunosuppression for organ transplantation. Lancet 361:1502–1510, 2003.

    PubMed Central  PubMed  Google Scholar 

  102. Sussman, E. M., M. C. Halpin, J. Muster, R. T. Moon, and B. D. Ratner. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann. Biomed. Eng. 1–9, 2013.

  103. Thomas, P. K. The connective tissue of peripheral nerve: an electron microscope study. J. Anat. 97:35–44, 1963.

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Tzanakakis, E. S., D. J. Hess, T. D. Sielaff, and W. S. Hu. Extracorporeal tissue engineered liver-assist devices. Annu. Rev. Biomed. Eng. 2:607–632, 2000.

    CAS  PubMed  Google Scholar 

  105. Unger, R. E., K. Peters, Q. Huang, A. Funk, D. Paul, and C. J. Kirkpatrick. Vascularization and gene regulation of human endothelial cells growing on porous polyethersulfone (PES) hollow fiber membranes. Biomaterials 26:3461–3469, 2005.

    CAS  PubMed  Google Scholar 

  106. Utzschneider, S., A. C. Paulus, C. Schroder, and V. Jansson. Possibilities and limits of modern polyethylenes: with respect to the application profile. Der Orthopade 43:515–521, 2014.

    CAS  PubMed  Google Scholar 

  107. Uygun, B. E., A. Soto-Gutierrez, H. Yagi, M. L. Izamis, M. A. Guzzardi, C. Shulman, J. Milwid, N. Kobayashi, A. Tilles, F. Berthiaume, M. Hertl, Y. Nahmias, M. L. Yarmush, and K. Uygun. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat. Med. 16:814–820, 2010.

    PubMed Central  CAS  PubMed  Google Scholar 

  108. Wang, J. H. Mechanobiology of tendon. J. Biomech. 39:1563–1582, 2006.

    PubMed  Google Scholar 

  109. Wang, T. Y., K. A. Bruggeman, R. K. Sheean, B. J. Turner, D. R. Nisbet, and C. L. Parish. Characterisation of the stability and bio-functionality of tethered proteins on bioengineered scaffolds: implications for stem cell biology and tissue repair. J. Biol. Chem. 289:15044–15051, 2014.

    CAS  PubMed  Google Scholar 

  110. Webber, M. J., J. Tongers, C. J. Newcomb, K. T. Marquardt, J. Bauersachs, D. W. Losordo, and S. I. Stupp. Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc. Natl. Acad. Sci. USA 108:13438–13443, 2011.

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Witkowski, P., H. Sondermeijer, M. A. Hardy, D. C. Woodland, K. Lee, G. Bhagat, K. Witkowski, F. See, A. Rana, A. Maffei, S. Itescu, and P. E. Harris. Islet grafting and imaging in a bioengineered intramuscular space. Transplantation 88:1065–1074, 2009.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Wu, W., X. Feng, T. Mao, H. W. Ouyang, G. Zhao, and F. Chen. Engineering of human tracheal tissue with collagen-enforced poly-lactic-glycolic acid non-woven mesh: a preliminary study in nude mice. Br. J. Oral. Maxillofac. Surg. 45:272–278, 2007.

    PubMed  Google Scholar 

  113. Yannas, I. V., J. F. Burke, D. P. Orgill, and E. M. Skrabut. Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. Science 215:174–176, 1982.

    CAS  PubMed  Google Scholar 

  114. Yeong, W. Y., C. K. Chua, K. F. Leong, and M. Chandrasekaran. Rapid prototyping in tissue engineering: challenges and potential. Trends Biotechnol. 22:643–652, 2004.

    CAS  PubMed  Google Scholar 

  115. Zhang, L., Z. Cao, T. Bai, L. Carr, J. R. Ella-Menye, C. Irvin, B. D. Ratner, and S. Jiang. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat. Biotechnol. 31:553–556, 2013.

    CAS  PubMed  Google Scholar 

  116. Zhao, L., V. K. Lee, S. S. Yoo, G. Dai, and X. Intes. The integration of 3-d cell printing and mesoscopic fluorescence molecular tomography of vascular constructs within thick hydrogel scaffolds. Biomaterials 33:5325–5332, 2012.

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

MJW acknowledges support from the National Institutes of Health (NIDDK) for support through a Ruth Kirschstein National Research Service Award (F32DK101335). BCT acknowledges support from the Juvenile Diabetes Research Foundation for a Postdoctoral Fellowship (3-2011-310).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert Langer.

Additional information

Associate Editor Nadya Lumelsky oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Webber, M.J., Khan, O.F., Sydlik, S.A. et al. A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering. Ann Biomed Eng 43, 641–656 (2015). https://doi.org/10.1007/s10439-014-1104-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-014-1104-7

Keywords

Navigation