Skip to main content

Advertisement

SpringerLink
Log in

Decellularized Allogeneic and Xenogeneic Tissue as a Bioscaffold for Regenerative Medicine: Factors that Influence the Host Response

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

Abstract

Biologic scaffold materials composed of mammalian extracellular matrix (ECM) are prepared by decellularization of source tissues harvested from either humans (allogeneic) or a variety of other (xenogeneic) species. These matrix scaffold materials are commonly regulated and used as surgical mesh materials for applications such as ventral hernia repair, musculotendinous tissue reconstruction, dura mater replacement, reconstructive breast surgery, pelvic floor reconstruction, and the treatment of cutaneous ulcers, among others. The clinical results for these applications vary widely for reasons which include characteristics of the source tissue, methods and efficacy of tissue decellularization, and methods of processing/manufacturing. However, the primary determinant of success or failure in the clinical setting is the response of the host to these implanted biologic scaffold materials. It is logical to question why any non-self biologic material, particularly a xenogeneic material, would not elicit an early and aggressive adverse immune response. The present manuscript briefly describes the known mechanisms by which these biologic scaffold materials can facilitate a constructive remodeling response, the known causative factors of an adverse response, and provides a general discussion of the role of the macrophage in determining outcome.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DAMP:

Damage associated molecular pattern

ECM:

Extracellular matrix

GAG:

Glycosaminoglycan

HMGB1:

High mobility group box 1

SIS:

Small intestinal submucosa

TE/RM:

Tissue Engineering and Regenerative Medicine

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor alpha

References

  1. Agrawal, V., S. A. Johnson, J. Reing, L. Zhang, S. Tottey, et al. Epimorphic regeneration approach to tissue replacement in adult mammals. Proc Natl Acad Sci U S A 107:3351–3355, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Alvarado, A. Regeneration in the metazoans: why does it happen? BioEssays 22:578–590, 2000.

    Article  CAS  Google Scholar 

  3. Anderson, J. M. Inflammatory response to implants. ASAIO Trans 34:101–107, 1988.

    Article  CAS  PubMed  Google Scholar 

  4. Anderson, J. M., A. Rodriguez, and D. T. Chang. Foreign body reaction to biomaterials. Semin Immunol 20:86–100, 2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Andrassy, M., H. C. Volz, J. C. Igwe, B. Funke, S. N. Eichberger, et al. High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation 117:3216–3226, 2008.

    Article  CAS  PubMed  Google Scholar 

  6. Badylak, S. F., T. Hoppo, A. Nieponice, T. W. Gilbert, J. M. Davison, and B. A. Jobe. Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold. Tissue Eng Part A 17:1643–1650, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Badylak, S., K. Kokini, B. Tullius, A. Simmons-Byrd, and R. Morff. Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Res 103:190–202, 2002.

    Article  PubMed  Google Scholar 

  8. Badylak, S., K. Kokini, B. Tullius, and B. Whitson. Strength over time of a resorbable bioscaffold for body wall repair in a dog model. J Surg Res 99:282–287, 2001.

    Article  CAS  PubMed  Google Scholar 

  9. Badylak, S. F., G. C. Lantz, A. Coffey, and L. A. Geddes. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res 47:74–80, 1989.

    Article  CAS  PubMed  Google Scholar 

  10. Badylak, S. F., K. Park, N. Peppas, G. McCabe, and M. Yoder. Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix. Exp Hematol 29:1310–1318, 2001.

    Article  CAS  PubMed  Google Scholar 

  11. Beattie, A. J., T. W. Gilbert, J. P. Guyot, A. J. Yates, and S. F. Badylak. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng Part A 15:1119–1125, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Brown, B. N., and S. F. Badylak. Expanded applications, shifting paradigms and an improved understanding of host-biomaterial interactions. Acta Biomater 9:4948–4955, 2013.

    Article  CAS  PubMed  Google Scholar 

  13. Brown, B. N., J. M. Freund, L. Han, J. P. Rubin, J. E. Reing, et al. Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Eng Part C Methods 17:411–421, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Brown, B. N., R. Londono, S. Tottey, L. Zhang, K. A. Kukla, et al. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater 8:978–987, 2012.

    Article  CAS  PubMed  Google Scholar 

  15. Brown, B. N., B. D. Ratner, S. B. Goodman, S. Amar, and S. F. Badylak. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33:3792–3802, 2012.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Brown, B. N., J. E. Valentin, A. M. Stewart-Akers, G. P. McCabe, and S. F. Badylak. Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials 30:1482–1491, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Cartmell, J. S., and M. G. Dunn. Effect of chemical treatments on tendon cellularity and mechanical properties. J Biomed Mater Res 49:134–140, 2000.

    Article  CAS  PubMed  Google Scholar 

  18. Choi, J. S., J. K. Williams, M. Greven, K. A. Walter, P. W. Laber, et al. Bioengineering endothelialized neo-corneas using donor-derived corneal endothelial cells and decellularized corneal stroma. Biomaterials 31:6738–6745, 2010.

    Article  CAS  PubMed  Google Scholar 

  19. Clough, A., J. Ball, G. S. Smith, and S. Leibman. Porcine small intestine submucosa matrix (Surgisis) for esophageal perforation. Ann Thorac Surg 91:e15–e16, 2011.

    Article  PubMed  Google Scholar 

  20. Cobb, M. A., S. F. Badylak, W. Janas, and F. A. Boop. 1996. Histology after dural grafting with small intestinal submucosa. Surg. Neurol. 46:389–393; discussion 93-4.

    Google Scholar 

  21. Colorado, P. C., A. Torre, G. Kamphaus, Y. Maeshima, H. Hopfer, et al. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 60:2520–2526, 2000.

    CAS  PubMed  Google Scholar 

  22. Crapo, P. M., T. W. Gilbert, and S. F. Badylak. An overview of tissue and whole organ decellularization processes. Biomaterials 32:3233–3243, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Daly, K., A. Stewart-Akers, H. Hara, M. Ezzelarab, C. Long, et al. Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng. Part A. 15(12), 3877–3888, 2009.

    Google Scholar 

  24. Daly, K. A., S. Liu, V. Agrawal, B. N. Brown, S. A. Johnson, et al. Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling. Biomaterials 33:91–101, 2012.

    Article  CAS  PubMed  Google Scholar 

  25. de Castro Bras, L. E., S. Shurey, and P. D. Sibbons. Evaluation of crosslinked and non-crosslinked biologic prostheses for abdominal hernia repair. Hernia 16:77–89, 2012.

    Article  PubMed Central  PubMed  Google Scholar 

  26. De Mori, R., S. Straino, A. Di Carlo, A. Mangoni, G. Pompilio, et al. Multiple effects of high mobility group box protein 1 in skeletal muscle regeneration. Arterioscler Thromb Vasc Biol 27:2377–2383, 2007.

    Article  PubMed  Google Scholar 

  27. Deeken, C. R., A. K. White, S. L. Bachman, B. J. Ramshaw, D. S. Cleveland, et al. 2010. Method of preparing a decellularized porcine tendon using tributyl phosphate. J. Biomed. Mater. Res. B Appl. Biomater.

  28. Dennis, C. Brief history of development of vascular grafts. In: Modern Vascular Grafts, edited by P. Sawyer. New York: McGraw-Hill, 1987, 326 pp.

  29. Dong, X., X. Wei, W. Yi, C. Gu, X. Kang, et al. 2009. RGD-modified acellular bovine pericardium as a bioprosthetic scaffold for tissue engineering. J. Mater. Sci. Mater. Med.

  30. Fitzpatrick, J. C., P. M. Clark, F. M. Capaldi. 2010. Effect of decellularization protocol on the mechanical behavior of porcine descending aorta. Int. J. Biomater. 2010.

  31. Flynn, L. E. 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, 2010.

    Article  CAS  PubMed  Google Scholar 

  32. Gilbert, T. W., M. S. Sacks, J. S. Grashow, S. L. Woo, S. F. Badylak, and M. B. Chancellor. Fiber kinematics of small intestinal submucosa under biaxial and uniaxial stretch. J Biomech Eng 128:890–898, 2006.

    Article  PubMed  Google Scholar 

  33. Gilbert, T. W., T. L. Sellaro, and S. F. Badylak. Decellularization of tissues and organs. Biomaterials 27:3675–3683, 2006.

    CAS  PubMed  Google Scholar 

  34. Gillies, A. R., L. R. Smith, R. L. Lieber, and S. Varghese. Method for decellularizing skeletal muscle without detergents or proteolytic enzymes. Tissue Eng Part C Methods 17:383–389, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Gordon, S., and P. R. Taylor. Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964, 2005.

    Article  CAS  PubMed  Google Scholar 

  36. Gratzer, P. F., R. D. Harrison, and T. Woods. Matrix alteration and not residual sodium dodecyl sulfate cytotoxicity affects the cellular repopulation of a decellularized matrix. Tissue Eng 12:2975–2983, 2006.

    Article  CAS  PubMed  Google Scholar 

  37. Grauss, R. W., M. G. Hazekamp, F. Oppenhuizen, C. J. van Munsteren, A. C. Gittenberger-de Groot, and M. C. DeRuiter. 2005. Histological evaluation of decellularised porcine aortic valves: matrix changes due to different decellularisation methods. Eur. J. Cardiothorac. Surg. 27:566–571.

  38. Ho, K. L., M. N. Witte, and E. T. Bird. 8-ply small intestinal submucosa tension-free sling: spectrum of postoperative inflammation. J Urol 171:268–271, 2004.

    Article  PubMed  Google Scholar 

  39. Hodde, J. P., S. F. Badylak, and K. D. Shelbourne. The effect of range of motion on remodeling of small intestinal submucosa (SIS) when used as an Achilles tendon repair material in the rabbit. Tissue Eng 3:27–37, 1997.

    Article  Google Scholar 

  40. Horowitz, B., R. Bonomo, A. M. Prince, S. N. Chin, B. Brotman, and R. W. Shulman. Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. Blood 79:826–831, 1992.

    CAS  PubMed  Google Scholar 

  41. Huang, M., N. Li, Z. Wu, P. Wan, X. Liang, et al. Using acellular porcine limbal stroma for rabbit limbal stem cell microenvironment reconstruction. Biomaterials 32:7812–7821, 2011.

    Article  CAS  PubMed  Google Scholar 

  42. Hudson, T. W., S. Y. Liu, and C. E. Schmidt. Engineering an improved acellular nerve graft via optimized chemical processing. Tissue Eng 10:1346–1358, 2004.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    Article  CAS  PubMed  Google Scholar 

  44. Lantz, G. C., S. F. Badylak, A. C. Coffey, L. A. Geddes, and W. E. Blevins. Small intestinal submucosa as a small-diameter arterial graft in the dog. J Invest Surg 3:217–227, 1990.

    Article  CAS  PubMed  Google Scholar 

  45. Lawrence, T., and G. Natoli. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761, 2011.

    Article  CAS  PubMed  Google Scholar 

  46. Levy, R. J., N. Vyavahare, M. Ogle, P. Ashworth, R. Bianco, and F. J. Schoen. 2003. Inhibition of cusp and aortic wall calcification in ethanol- and aluminum-treated bioprosthetic heart valves in sheep: background, mechanisms, and synergism. J. Heart Valve Dis. 12:209–216; discussion 16.

    Google Scholar 

  47. Liao, J., L. Yang, J. Grashow, and M. S. Sacks. The relation between collagen fibril kinematics and mechanical properties in the mitral valve anterior leaflet. J Biomech Eng 129:78–87, 2007.

    Article  PubMed  Google Scholar 

  48. Limana, F., A. Germani, A. Zacheo, J. Kajstura, A. Di Carlo, et al. Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation. Circ Res 97:e73–e83, 2005.

    Article  CAS  PubMed  Google Scholar 

  49. Lolmede, K., L. Campana, M. Vezzoli, L. Bosurgi, R. Tonlorenzi, et al. Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways. J Leukoc Biol 85:779–787, 2009.

    Article  CAS  PubMed  Google Scholar 

  50. Longaker, M. T., M. R. Harrison, T. M. Crombleholme, J. C. Langer, M. Decker, et al. Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid. J Pediatr Surg 24:789–792, 1989.

    Article  CAS  PubMed  Google Scholar 

  51. Longaker, M. T., D. J. Whitby, M. W. Ferguson, M. R. Harrison, T. M. Crombleholme, et al. Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing. J Pediatr Surg 24:799–805, 1989.

    Article  CAS  PubMed  Google Scholar 

  52. Lumpkins, S. B., N. Pierre, and P. S. McFetridge. A mechanical evaluation of three decellularization methods in the design of a xenogeneic scaffold for tissue engineering the temporomandibular joint disc. Acta Biomater 4:808–816, 2008.

    Article  PubMed  Google Scholar 

  53. Lynch, A. P., and M. Ahearne. Strategies for developing decellularized corneal scaffolds. Exp Eye Res 108:42–47, 2013.

    Article  CAS  PubMed  Google Scholar 

  54. Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, and M. Locati. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686, 2004.

    Article  CAS  PubMed  Google Scholar 

  55. Martin, P., and J. Lewis. Actin cables and epidermal movement in embryonic wound healing. Nature 360:179–183, 1992.

    Article  CAS  PubMed  Google Scholar 

  56. McPherson, T. B., H. Liang, R. D. Record, and S. F. Badylak. Galalpha(1,3)Gal epitope in porcine small intestinal submucosa. Tissue Eng 6:233–239, 2000.

    Article  CAS  PubMed  Google Scholar 

  57. Meyer, S. R., B. Chiu, T. A. Churchill, L. Zhu, J. R. Lakey, and D. B. Ross. Comparison of aortic valve allograft decellularization techniques in the rat. J Biomed Mater Res A 79:254–262, 2006.

    Article  PubMed  Google Scholar 

  58. Mills, C. D., K. Kincaid, J. M. Alt, M. J. Heilman, and A. M. Hill. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173, 2000.

    Article  CAS  PubMed  Google Scholar 

  59. Montoya, C. V., and P. S. McFetridge. Preparation of ex vivo-based biomaterials using convective flow decellularization. Tissue Eng Part C Methods 15:191–200, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Morgan, T. Regeneration in the Egg, Embryo, and Adult. The American Naturalist 35:949–979, 1901.

    Article  Google Scholar 

  61. Mosser, D. M., and J. P. Edwards. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969, 2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Musahl, V., S. D. Abramowitch, T. W. Gilbert, E. Tsuda, J. H. Wang, et al. The use of porcine small intestinal submucosa to enhance the healing of the medial collateral ligament—a functional tissue engineering study in rabbits. J Orthop Res 22:214–220, 2004.

    Article  PubMed  Google Scholar 

  63. Nakayama, K. H., C. A. Batchelder, C. I. Lee, and A. F. Tarantal. Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng Part A 16:2207–2216, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. O’Neill, J. D., R. Anfang, A. Anandappa, J. Costa, J. Javidfar, et al. Decellularization of human and porcine lung tissues for pulmonary tissue engineering. Ann Thorac Surg 96:1046–1055; discussion 55–56. 2013.

    Google Scholar 

  65. O’Reilly, M. S., T. Boehm, Y. Shing, N. Fukai, G. Vasios, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285, 1997.

    Article  PubMed  Google Scholar 

  66. Ozeki, M., Y. Narita, H. Kagami, N. Ohmiya, A. Itoh, et al. Evaluation of decellularized esophagus as a scaffold for cultured esophageal epithelial cells. J Biomed Mater Res A 79:771–778, 2006.

    Article  PubMed  Google Scholar 

  67. Petersen, T. H., E. A. Calle, M. B. Colehour, and L. E. Niklason. Matrix composition and mechanics of decellularized lung scaffolds. Cells Tissues Organs 195:222–231, 2012.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Petersen, T. H., E. A. Calle, L. Zhao, E. J. Lee, L. Gui, et al. Tissue-engineered lungs for in vivo implantation. Science 329:538–541, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Petter-Puchner, A. H., R. H. Fortelny, R. Mittermayr, N. Walder, W. Ohlinger, and H. Redl. Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair. Surg Endosc 20:942–946, 2006.

    Article  CAS  PubMed  Google Scholar 

  70. Ponce Marquez, S., V. S. Martinez, W. McIntosh Ambrose, J. Wang, N. G. Gantxegui, et al. Decellularization of bovine corneas for tissue engineering applications. Acta Biomater 5:1839–1847, 2009.

    Article  PubMed  Google Scholar 

  71. Porto, A., R. Palumbo, M. Pieroni, G. Aprigliano, R. Chiesa, et al. Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein. FASEB J 20:2565–2566, 2006.

    Article  CAS  PubMed  Google Scholar 

  72. Prasertsung, I., S. Kanokpanont, T. Bunaprasert, V. Thanakit, and S. Damrongsakkul. Development of acellular dermis from porcine skin using periodic pressurized technique. J Biomed Mater Res B Appl Biomater 85:210–219, 2008.

    Article  PubMed  Google Scholar 

  73. Ramchandran, R., M. Dhanabal, R. Volk, M. J. Waterman, M. Segal, et al. Antiangiogenic activity of restin, NC10 domain of human collagen XV: comparison to endostatin. Biochem Biophys Res Commun 255:735–739, 1999.

    Article  CAS  PubMed  Google Scholar 

  74. Ranzato, E., M. Patrone, M. Pedrazzi, and B. Burlando. HMGb1 promotes scratch wound closure of HaCaT keratinocytes via ERK1/2 activation. Mol Cell Biochem 332:199–205, 2009.

    Article  CAS  PubMed  Google Scholar 

  75. Record, R. D., D. Hillegonds, C. Simmons, R. Tullius, F. A. Rickey, et al. In vivo degradation of 14C-labeled small intestinal submucosa (SIS) when used for urinary bladder repair. Biomaterials 22:2653–2659, 2001.

    Article  CAS  PubMed  Google Scholar 

  76. Reing, J. E., B. N. Brown, D. A. Daly, J. M. Freund, T. W. Gilbert, et al. The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds. Biomaterials 31:8626–8633, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Reing, J. E., L. Zhang, J. Myers-Irvin, K. E. Cordero, D. O. Freytes, et al. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng Part A 15:605–614, 2009.

    Article  CAS  PubMed  Google Scholar 

  78. Rieder, E., M. T. Kasimir, G. Silberhumer, G. Seebacher, E. Wolner, et al. Decellularization protocols of porcine heart valves differ importantly in efficiency of cell removal and susceptibility of the matrix to recellularization with human vascular cells. J Thorac Cardiovasc Surg 127:399–405, 2004.

    Article  PubMed  Google Scholar 

  79. Sarikaya, A., R. Record, C. C. Wu, B. Tullius, S. Badylak, and M. Ladisch. Antimicrobial activity associated with extracellular matrices. Tissue Eng 8:63–71, 2002.

    Article  PubMed  Google Scholar 

  80. Sheridan, W. S., G. P. Duffy, and B. P. Murphy. Mechanical characterization of a customized decellularized scaffold for vascular tissue engineering. J Mech Behav Biomed Mater 8:58–70, 2012.

    Article  CAS  PubMed  Google Scholar 

  81. Sicari, B. M., S. A. Johnson, B. F. Siu, P. M. Crapo, K. A. Daly, et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials 33:5524–5533, 2012.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Stout, R. D., S. K. Watkins, and J. Suttles. Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages. J Leukoc Biol 86:1105–1109, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Thomas, J. O. HMG1 and 2: architectural DNA-binding proteins. Biochem Soc Trans 29:395–401, 2001.

    Article  CAS  PubMed  Google Scholar 

  84. Tian, J., A. M. Avalos, S. Y. Mao, B. Chen, K. Senthil, et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496, 2007.

    Article  CAS  PubMed  Google Scholar 

  85. Tottey, S., S. A. Johnson, P. M. Crapo, J. E. Reing, L. Zhang, et al. The effect of source animal age upon extracellular matrix scaffold properties. Biomaterials 32:128–136, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Turner, N. J., A. J. Yates, Jr, D. J. Weber, I. R. Qureshi, D. B. Stolz, et al. Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. Tissue Eng Part A 16:3309–3317, 2010.

    Article  CAS  PubMed  Google Scholar 

  87. Uygun, B. E., A. Soto-Gutierrez, H. Yagi, M. L. Izamis, M. A. Guzzardi, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16:814–820, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Valentin, J. E., A. M. Stewart-Akers, T. W. Gilbert, and S. F. Badylak. Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A 15:1687–1694, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Valentin, J. E., N. J. Turner, T. W. Gilbert, and S. F. Badylak. Functional skeletal muscle formation with a biologic scaffold. Biomaterials 31:7475–7484, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Vavken, P., S. Joshi, and M. M. Murray. TRITON-X is most effective among three decellularization agents for ACL tissue engineering. J Orthop Res 27:1612–1618, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Whitby, D. J., and M. W. Ferguson. The extracellular matrix of lip wounds in fetal, neonatal and adult mice. Development 112:651–668, 1991.

    CAS  PubMed  Google Scholar 

  92. Woods, T., and P. F. Gratzer. Effectiveness of three extraction techniques in the development of a decellularized bone-anterior cruciate ligament-bone graft. Biomaterials 26:7339–7349, 2005.

    Article  CAS  PubMed  Google Scholar 

  93. Xu, C. C., R. W. Chan, and N. Tirunagari. A biodegradable, acellular xenogeneic scaffold for regeneration of the vocal fold lamina propria. Tissue Eng. 2006.

  94. Yang, D., Q. Chen, H. Yang, K. J. Tracey, M. Bustin, and J. J. Oppenheim. High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. J Leukoc Biol 81:59–66, 2007.

    Article  CAS  PubMed  Google Scholar 

  95. Zhang, A. Y., S. J. Bates, E. Morrow, H. Pham, B. Pham, and J. Chang. Tissue-engineered intrasynovial tendons: optimization of acellularization and seeding. J Rehabil Res Dev 46:489–498, 2009.

    Article  PubMed  Google Scholar 

  96. Zhang, Q., M. Raoof, Y. Chen, Y. Sumi, T. Sursal, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Zhou, J., O. Fritze, M. Schleicher, H. P. Wendel, K. Schenke-Layland, et al. Impact of heart valve decellularization on 3-D ultrastructure, immunogenicity and thrombogenicity. Biomaterials 31:2549–2554, 2010.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Author information

Authors and Affiliations

  1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA, 15219-3130, USA

    Stephen F. Badylak

  2. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Stephen F. Badylak

  3. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    Stephen F. Badylak

Authors
  1. Stephen F. Badylak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen F. Badylak.

Additional information

Associate Editor Song Li oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Badylak, S.F. Decellularized Allogeneic and Xenogeneic Tissue as a Bioscaffold for Regenerative Medicine: Factors that Influence the Host Response. Ann Biomed Eng 42, 1517–1527 (2014). https://doi.org/10.1007/s10439-013-0963-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-013-0963-7

Keywords

Search

Navigation