Tissue engineering tools for modulation of the immune response

BioTechniques

Volumn 51, Issue 4, 2011, Pages 239-254

  Boehler, Ryan M ^a   Graham, John G ^a   Shea, Lonnie D ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Biomaterials; Cell transplantation; Gene delivery; Immune modulation; Immune response; Tissue engineering

Indexed keywords

CORTICOSTEROID; DNA; GAMMA INTERFERON; GROWTH FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; NONSTEROID ANTIINFLAMMATORY AGENT; POLYMER; REACTIVE OXYGEN METABOLITE; RNA; TISSUE SCAFFOLD; TUMOR NECROSIS FACTOR ALPHA;

ANTIGEN PRESENTING CELL; BIODEGRADABILITY; CD4+ CD25+ T LYMPHOCYTE; CELL ADHESION; CELL DIFFERENTIATION; CELL INFILTRATION; CELL INTERACTION; CELL MATURATION; CELL MIGRATION; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; DRUG DELIVERY SYSTEM; EXTRACELLULAR MATRIX; FIBROBLAST; FOREIGN BODY REACTION; GENE DELIVERY SYSTEM; GRANULATION TISSUE; HYDROGEL; IMMUNE RESPONSE; IMMUNITY; IMMUNOGENICITY; IMMUNOMODULATION; IMPLANT; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; LEUKOCYTE ADHERENCE; MONOCYTE; NEUTROPHIL; NONVIRAL GENE DELIVERY SYSTEM; PHAGOCYTOSIS; PROTEIN CROSS LINKING; PROTEIN STABILITY; PROTEIN TRANSPORT; REGENERATIVE MEDICINE; REGULATORY T LYMPHOCYTE; REVIEW; RNA INTERFERENCE; SCAR FORMATION; STEM CELL TRANSPLANTATION; TH1 CELL; TH2 CELL; TISSUE ENGINEERING; TISSUE INJURY; TISSUE REGENERATION; WOUND HEALING; XENOGRAFT;

ADAPTIVE IMMUNITY; BIOCOMPATIBLE MATERIALS; CELL CULTURE TECHNIQUES; CELL TRANSPLANTATION; CYTOKINES; GENE TRANSFER TECHNIQUES; HUMANS; IMMUNITY, INNATE; IMMUNOLOGIC FACTORS; IMMUNOMODULATION; INFLAMMATION; REGENERATIVE MEDICINE; STEM CELLS; TISSUE ENGINEERING; TISSUE SCAFFOLDS;

EID: 80054098005     PISSN: 07366205     EISSN: 19409818     Source Type: Journal    
DOI: 10.2144/000113754     Document Type: Review

References (82)

1. Donnelly, D.J. and P.G. Popovich. 2008. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol. 209:378-388.
2. Tidball, J.G. and M. Wehling-Henricks. 2007. Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J. Physiol. 578:327-336.
3. De Laporte, L. and L.D. Shea. 2007. Matrices and scaffolds for DNA delivery in tissue engineering. Adv. Drug Deliv. Rev. 59:292-307.
4. Drury, J.L. and D.J. Mooney. 2003. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337-4351.
5. Anderson, J.M., A. Rodriguez, and D.T. Chang. 2008. Foreign body reaction to biomaterials. Semin. Immunol. 20:86-100.
6. Diegelmann, R.F. and M.C. Evans. 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9:283-289.
7. Jones, K.S. 2008. Effects of biomaterial-induced inflammation on fibrosis and rejection. Semin. Immunol. 20:130-136.
8. Nilsson, B., K.N. Ekdahl, T.E. Mollnes, and J.D. Lambris. 2007. The role of complement in biomaterial-induced inflammation. Mol. Immunol. 44:82-94.
9. Lopez-Armada, M.J., O. Sanchez-Pernaute, R. Largo, I. Diez-Ortego, I. Palacios, J. Egido, and G. Herrero-Beaumont. 2002. Modulation of cell recruitment by anti-inflammatory agents in antigen-induced arthritis. Ann. Rheum. Dis. 61:1027-1030.
10. Gonzalez, R., J. Glaser, M.T. Liu, T.E. Lane, and H.S. Keirstead. 2003. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp. Neurol. 184:456-463.
11. Beck, K.D., H.X. Nguyen, M.D. Galvan, D.L. Salazar, T.M. Woodruff, and A.J. Anderson. 2010. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain 133:433-447.
12. Pineau, I. and S. Lacroix. 2007. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J. Comp. Neurol. 500:267-285.
13. Duffield, J.S. 2003. The inflammatory macrophage: a story of Jekyll and Hyde. Clin. Sci. (Lond.) 104:27-38.
14. Xu, W., A. Roos, N. Schlagwein, A.M. Woltman, M.R. Daha, and C. van Kooten. 2006. IL-10-producing macrophages preferentially clear early apoptotic cells. Blood 107:4930-4937.
15. Martinez, F.O., A. Sica, A. Mantovani, and M. Locati. 2008. Macrophage activation and polarization. Front. Biosci. 13:453-461.
16. Yoon, Y.S., A. Wecker, L. Heyd, J.S. Park, T. Tkebuchava, K. Kusano, A. Hanley, H. Scadova, et al. 2005. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J. Clin. Invest. 115:326-338.
17. Shapiro, A.M., J.R. Lakey, E.A. Ryan, G.S. Korbutt, E. Toth, G.L. Warnock, N.M. Kneteman, and R.V. Rajotte. 2000. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343:230-238.
18. Hering, B.J., M. Wijkstrom, M.L. Graham, M. Hardstedt, T.C. Aasheim, T. Jie, J.D. Ansite, M. Nakano, et al. 2006. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat. Med. 12:301-303.
19. Kirchhof, N., S. Shibata, M. Wijkstrom, D.M. Kulick, C.T. Salerno, S.M. Clemmings, Y. Heremans, U. Galili, et al. 2004. Reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection. Xenotransplantation 11:396-407.
20. Corbett, J.A., M.A. Sweetland, J.L. Wang, J.R. Lancaster, Jr., and M.L. McDaniel. 1993. Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc. Natl. Acad. Sci. USA 90:1731-1735.
21. Fu, F., Y. Li, S. Qian, L. Lu, F. Chambers, T.E. Starzl, J.J. Fung, and A.W. Thomson. 1996. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation 62:659-665.
22. Ito, T., M. Yang, Y.H. Wang, R. Lande, J. Gregorio, O.A. Perng, X.F. Qin, Y.J. Liu, and M. Gilliet. 2007. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204:105-115.
23. Mellor, A.L. and D.H. Munn. 2008. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat. Rev. Immunol. 8:74-80.
24. Houchin-Ray, T., A. Huang, E.R. West, M. Zelivyanskaya, and L.D. Shea. 2009. Spatially patterned gene expression for guided neurite extension. J. Neurosci. Res. 87:844-856.
25. Gu, Z., A. Biswas, M. Zhao, and Y. Tang. 2011. Tailoring nanocarriers for intracellular protein delivery. Chem. Soc. Rev. 40:3638-3655.
26. Richardson, T.P., M.C. Peters, A.B. Ennett, and D.J. Mooney. 2001. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19:1029-1034.
27. Putney, S.D. and P.A. Burke. 1998. Improving protein therapeutics with sustained-release formulations. Nat. Biotechnol. 16:153-157.
28. Edwards, C.K., 3rd, S.W. Martin, J. Seely, O. Kinstler, S. Buckel, A.M. Bendele, M. Ellen Cosenza, U. Feige, and T. Kohno. 2003. Design of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) for chronic inflammatory diseases. Adv. Drug Deliv. Rev. 55:1315-1336.
29. Alemany, R., K. Suzuki, and D.T. Curiel. 2000. Blood clearance rates of adenovirus type 5 in mice. J. Gen. Virol. 81:2605-2609.
30. Lei, Y., S. Huang, P. Sharif-Kashani, Y. Chen, P. Kavehpour, and T. Segura. 2010. Incorporation of active DNA/cationic polymer polyplexes into hydrogel scaffolds. Biomaterials 31:9106-9116.
31. Jewell, C.M. and D.M. Lynn. 2008. Multilayered polyelectrolyte assemblies as platforms for the delivery of DNA and other nucleic acid-based therapeutics. Adv. Drug Deliv. Rev. 60:979-999.
32. Aviles, M.O., C.H. Lin, M. Zelivyanskaya, J.G. Graham, R.M. Boehler, P.B. Messersmith, and L.D. Shea. 2010. The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds. Biomaterials 31:1140-1147.
33. De Laporte, L., A. Huang, M.M. Ducommun, M.L. Zelivyanska, M.O. Aviles, A.F. Adler, and L.D. Shea. 2010. Patterned transgene expression in multiple-channel bridges after spinal cord injury. Acta Biomater. 6:2889-2897.
34. Phillips, J.E., K.L. Burns, J.M. Le Doux, R.E. Guldberg, and A.J. Garcia. 2008. Engineering graded tissue interfaces. Proc. Natl. Acad. Sci. USA 105:12170-12175.
35. Kako, K., M. Nishikawa, H. Yoshida, and Y. Takakura. 2008. Effects of inflammatory response on in vivo transgene expression by plasmid DNA in mice. J. Pharm. Sci. 97:3074-3083.
36. Hyde, S.C., I.A. Pringle, S. Abdullah, A.E. Lawton, L.A. Davies, A. Varathalingam, G. Nunez-Alonso, A.M. Green, et al. 2008. CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nat. Biotechnol. 26:549-551.
37. Jang, J.H., D.V. Schaffer, and L.D. Shea. 2011. Engineering biomaterial systems to enhance viral vector gene delivery. Mol. Ther. 19:1407-1415.
38. Strayer, D.S. 1999. Viral gene delivery. Expert Opin. Investig. Drugs 8:2159-2172.
39. Beer, S.J., C. B.Matthews, C.S. Stein, B.D. Ros, J. M. Hilfinger, and B.L. Davidson.1998. Poly (lactic-glycoli) acid copolymer enc apsul ation of rec ombinant adenov iru s reduces immu nogenicity in vivo. G ene Ther. 5:740-746.
40. Sakurai, H. F., Sakurai, K., Kawabata T., sasaki N., Koizumi H., Hang, K., Tashiro S., Kurachi, et al. 2007. C omparison of geneexpression efficiency and innat eimmun eresponse in duced by A dvector and lipoplex. J. Con trol. Release 11:430-437.
41. Croyle, M.A., N. Chirmule, Y. Zhang, and J.M. Wilson.2001. Stealth adenovir uses blun t cell- med iated and hu mor al immun e res ponse s against the vir us and allow for significant gene ex pression upon re admi nistrati on in the lung. J. Virl. 75:4792-4801.
42. Minozzi, F., N.C. Hasbrouck, E. Basner-Tschakarjan, S.A. Edmonson, D. J. Hi, D E. Sabtino, S. Zhu, J.F. Wright, et al. 2007. Modulation of tolerance to the transgene product in an onhum an primate model of AAV-mediatedgenetra nsfer to lier. B lood 110: 233 4-23 41.
43. Dai, Y., E.M. Scharz, D. Gu, W.W Zhang, N. Sarvetnick, an I. M. Vermaa. 1995. Cellul ar and h umo ral immune resp onses to adenov ira l vector sconta ining facto rIX gene: toler iza tion o f factor IX and vect or ant igens al lows for long-term expression. Proc. Natl. Acad. Sci. USA 9:1401-1105.
44. Bessis, N., F.J. GarciaCozar, and M.C. Boissier. 2004. Immuner esponses to gene therapy vectors: influence on vector function and effector mechanisms. Gene Ther. 11(Suppl 1):S10-S17.
45. Hezi-Yamit, A., C. Sullivan, J. Wong, L David, M. Chen, P. Cheng, D. Shumaker,J.N. Wilcox, and K. Udipi. 2009. Impa ct o f poly mer hydro philicit y on biocom at ibility: implicat ion f or DES pol ymer design. J. Biome d. Mat er. Res. A 9:133-141.
46. Jones, J.A., D.T Chang, H. Meyerson, E. Colton, I. K. Kwon, T.M atsuda, and J.M. Anerson. 2007. Proteo micanalysis and quantif ication of cyto kines and che mokines from bioma terial surface-adherent macrophages and foreign body giant cells. J. Biomed. M ater. Re s. A 83:5 85-596.
47. Rodriguez, A. H. Meyrson, and J.M. Anerson. 2009. Quantitative in vivo cytokine analys is at synthtic biomaterial implant sites. J. Biome d. Ma ter. Res. A 89:152- 159.
48. Brown, B.N., J.E. Valentin, A. M. Stewart-Akrs, G.P. McCabe, and S.F. Badylak. 2009. Macrop hagep henotype and remodeling out comes in response to biologic scaff olds with and with out a cellular component. Biomaterials 30:1 82-1491.
49. Babensee, J.E. and A. Paranjpe. 2005. Differential levels of dendritic cell matur ationon different biom aterials used incom bination products. J. Biomed. Ma ter. R es. A 74:503-510.
50. Acharya, A. P., N.V. Dolgova, M.J Clare-Salzler, B.G. Keselowsky. 2008. Adhe sivesubstrate-modulation of adaptive immunere sponses. Biomaterils 29:4736-4750.
51. Cao H., K. McHugh, S.Y. Chew, and J.M. Anderson. 2010. Thetopo grahical effect of electrospun nanofi brous scaffolds on the in vivo and in vitro foreign body reac tion. J. Biomed. Mate r. R es. A 93:1151-1159.
52. Chen, S., J.A. J nes, Y. Xu, H. Y. Low, J.M. Anderso, and K.W. Leong. 2010. Character ization of topographical effects on macrophage behavior in a foreign body response model. Bio materials 31:3479-3491.
53. Paul, N.E., C. Skazik, M. Harwardt, M. Bartnck, B. Denecke, D. Klee, J. Salber, and G. Zwadlo-Klarwasser. 2008. Topographical control of humanmacr ophages by ar egularlym icrostruct ured plyviny lidene fluorides rface. Biomaterials 29:4056-4064.
54. Bota, P.C., A.M. Collie, P Puolakkainen, R.B. Vernn, E.H. Sage, B.D. Ratner and P.S. Stayto. 2010. Biomaterial topography alters healing in vivo and mon ocyte/macr ophage activation in vitro. J. Biomed. Mater. Res. A 95: 649-657
55. Kou, P.M. and J.E. Babensee. 2011. Macrophag eand dendritic c ell phenotypic diversity in thcontext of biomaterials. J. Biomed. M ate r. Res. A 96:239-260.
56. Bridges, A.W., N. Singh, K.L. Burns, J.E. Babensee, L. Andrew Lyon, and A. J. Garcia. 2008. Reduced acute inflam matoryre sponses to microgel confomal coatings. Biom aterials 29:4 605-4615.
57. Liu, L., G. Chen, T. Chao, B. D. Ratner, E.H. Sage, and S.J ang. 2008. Reduced foreign body reaction to implanted biomaterials by surfacetreatment with oriented osteopontin. J. Biomater. Sci. Polym. Ed. 1:821-835.
58. Wang, S. A.S. Gupta, S. Sagnella, P.M. Barendt, K. Kottke-Marhant, and R.E. Marchant. 2009. Biomimetic fluorocarbo surfactant polymersreduce platelet adhesionon PT FE/ePTFE surfaces. J. Bio mater. Sci. Polym. Ed. 20:61-635.
59. Weaver, L.C., D. Gris, L.R. S aville, M.A. Oatway, Y. Chen, D R. Marsh, E.F. Hami lton, and G.A. De kaban. 2005. Methylp rednisolon ecauses minimal improvement after spinal cord injury inrats, contrasting with benfits of ananti-integrin treatment. J. Neu rotrau ma 22:13 75-1387.
60. Buti, E., A Bergami A. Recchia, E. Bramilla, U. Del Carro, S. Amadio, A. Cattalini, M. Esposito, et al. 2008. IL4 gene delivery to the CNS recruits regula tory T cells and induce s clini cal r ecove ry in mou se m odels of mul tiple sclerosis. Ge ne Ther. 15:504-515.
61. Fleming, J.C., F. Bao, Y. C hen, E.F. Hamilton, J.K. Relton, and L.C. Weaver. 2008. Alp ha4beta1 integrin blockade after spinal cord injury decreases damage and impr oves neurologicalfun ction. Ex p. Neurol. 214:14 7-159.
62. Chvatal, S. A., Y.T. Kim, A.M. Bratt-Leal, H. Lee, and R.V. Bellamkona. 2008. Spatial distribution and acute ant i-inflam matory effects of Methyl predni solone a fters ustained local delivery to the contuse dspinal cord. Bi omaterials 29: 1967-1975.
63. Blanco, E., B.D Weinberg, N.T. Stowe, J.M. Anderso, and J. Gao.2006. Localrel ease of dexamethasone from polymermillirods effectively pre vents fibros is a fterr adiofr equencyab lation. J. Bio med. Mater. Res. A 76:174-182.
64. Norton, L.W., J. Park, and J.E. Babensee. 2010. Biomaterialadjuvant effect is attenuated by anti-inflammatory drugdelivery or materialselection. J. Contr ol. Re lease 146:3 41-34.
65. Wilson, H.M., S. Chettibi, C. Jbin, D. Walbam, A.J. Rees, and D.C. Kluth. 2005. I nhibi ionofm acrophage nuclear factor-kappaBleads to a dominant anti-inflammatory pheno type that attenuatesglomeru larinflammation in vivo. Am. J. Pathol. 16 7:27-37.
66. Ghivizzani, S.C., E.R. Lechman, R. Kang, C. Tio, J. K olls, C.H. Evans, and P.D. Robbins. 1998. Di rect adenovirus-medi ated ge ne transfer of inte rleukin 1 a nd t umor necrosis f actor al pha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects. Proc. Natl. Acad. Sci. USA 95:4613-4618.
67. Peranteau, W.H., L. Zhang, N. Muvarak, A.T. Badillo, A. Radu, P.W. Zoltick, and K.W. Liechty. 2008. IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation. J. Invest. Dermatol. 128:1852-1860.
68. Cua, D.J., B. Hutchins, D.M. LaFace, S.A. Stohlman, and R.L. Coffman. 2001. Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J. Immunol. 166:602-608.
69. Goudy, K., S. Song, C. Wasserfall, Y.C. Zhang, M. Kapturczak, A. Muir, M. Powers, M. Scott-Jorgensen, et al. 2001. Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice. Proc. Natl. Acad. Sci. USA 98:13913-13918.
70. Prud'homme, G.J. 2000. Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors. J. Gene Med. 2:222-232.
71. Croxford, J.L., M. Feldmann, Y. Chernajovsky, and D. Baker. 2001. Different therapeutic outcomes in experimental allergic encephalomyelitis dependent upon the mode of delivery of IL-10: a comparison of the effects of protein, adenoviral or retroviral IL-10 delivery into the central nervous system. J. Immunol. 166:4124-4130.
72. Marion, N.W. and J.J. Mao. 2006. Mesenchymal stem cells and tissue engineering. Methods Enzymol. 420:339-361.
73. Berman, D.M., M.A. Willman, D. Han, G. Kleiner, N.M. Kenyon, O. Cabrera, J.A. Karl, R.W. Wiseman, et al. 2010. Mesenchymal stem cells enhance allogeneic islet engraftment in nonhuman primates. Diabetes 59:2558-2568.
74. Bartholomew, A., D. Polchert, E. Szilagyi, G.W. Douglas, and N. Kenyon. 2009. Mesenchymal stem cells in the induction of transplantation tolerance. Transplantation 87:S55-S57.
75. Di Nicola, M., C. Carlo-Stella, M. Magni, M. Milanesi, P.D. Longoni, P. Matteucci, S. Grisanti, and A.M. Gianni. 2002. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838-3843.
76. Dufour, J.M., S.J. Lord, T. Kin, G.R. Rayat, D.E. Dixon, R.C. Bleackley, G.S. Korbutt, and R.V. Rajotte. 2008. Comparison of successful and unsuccessful islet/Sertoli cell cotransplant grafts in streptozotocin-induced diabetic mice. Cell Transplant. 16:1029-1038.
77. Garrovillo, M., A. Ali, and S.F. Oluwole. 1999. Indirect allorecognition in acquired thymic tolerance: induction of donor-specific tolerance to rat cardiac allografts by allopeptide-pulsed host dendritic cells. Transplantation 68:1827-1834.
78. Luo, X., K.V. Tarbell, H. Yang, K. Pothoven, S.L. Bailey, R. Ding, R.M. Steinman, and M. Suthanthiran. 2007. Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 104:2821-2826.
79. Zhang, N., B. Schroppel, G. Lal, C. Jakubzick, X. Mao, D. Chen, N. Yin, R. Jessberger, et al. 2009. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity 30:458-469.
80. Kennedy, M.K., L.J. Tan, M.C. Dal Canto, V.K. Tuohy, Z.J. Lu, J.L. Trotter, and S.D. Miller. 1990. Inhibition of murine relapsing experimental autoimmune encephalomyelitis by immune tolerance to proteolipid protein and its encephalitogenic peptides. J. Immunol. 144:909-915.
81. Luo, X., K.L. Pothoven, D. McCarthy, M. DeGutes, A. Martin, D.R. Getts, G. Xia, J. He, et al. 2008. ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms. Proc. Natl. Acad. Sci. USA 105:14527-14532.
82. Kheradmand, T., S. Wang, R.F. Gibly, X. Zhang, S. Holland, J. Tasch, J.G. Graham, D.B. Kaufman, et al. 2011. Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions. Biomaterials 32:4517-4524.