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Injectable Acellular Hydrogels for Cardiac Repair

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Abstract

Injectable hydrogels are being developed as potential translatable materials to influence the cascade of events that occur after myocardial infarction. These hydrogels, consisting of both synthetic and natural materials, form through numerous chemical crosslinking and assembly mechanisms and can be used as bulking agents or for the delivery of biological molecules. Specifically, a range of materials are being applied that alter the resulting mechanical and biological signals after infarction and have shown success in reducing stresses in the myocardium and limiting the resulting adverse left ventricular (LV) remodeling. Additionally, the delivery of molecules from injectable hydrogels can influence cellular processes such as apoptosis and angiogenesis in cardiac tissue or can be used to recruit stem cells for repair. There is still considerable work to be performed to elucidate the mechanisms of these injectable hydrogels and to optimize their various properties (e.g., mechanics and degradation profiles). Furthermore, although the experimental findings completed to date in small animals are promising, future work needs to focus on the use of large animal models in clinically relevant scenarios. Interest in this therapeutic approach is high due to the potential for developing percutaneous therapies to limit LV remodeling and to prevent the onset of congestive heart failure that occurs with loss of global LV function. This review focuses on recent efforts to develop these injectable and acellular hydrogels to aid in cardiac repair.

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References

  1. Gheorghiade, M., & Bonow, R. O. (1998). Chronic heart failure in the United States—A manifestation of coronary artery disease. Circulation, 97(3), 282–289.

    PubMed  CAS  Google Scholar 

  2. Eaton, L. W., Weiss, J. L., Bulkley, B. H., Garrison, J. B., & Weisfeldt, M. L. (1979). Regional cardiac dilatation after acute myocardial-infarction—Recognition by 2-dimensional echocardiography. The New England Journal of Medicine, 300(2), 57–62.

    Article  PubMed  CAS  Google Scholar 

  3. Erlebacher, J. A., Weiss, J. L., Weisfeldt, M. L., & Bulkley, B. H. (1984). Early dilation of the infarcted segment in acute transmural myocardial-infarction—Role of infarct expansion in acute left-ventricular enlargement. Journal of the American College of Cardiology, 4(2), 201–208.

    Article  PubMed  CAS  Google Scholar 

  4. Weisman, H. F., & Healy, B. (1987). Myocardial infarct expansion, infarct extension, and reinfarction—Pathophysiologic concepts. Progress in Cardiovascular Diseases, 30(2), 73–110.

    Article  PubMed  CAS  Google Scholar 

  5. Epstein, F. H., Yang, Z. Q., Gilson, W. D., Berr, S. S., Kramer, C. M., & French, B. A. (2002). MR tagging early after myocardial infarction in mice demonstrates contractile dysfunction in adjacent and remote regions. Magnetic Resonance in Medicine, 48(2), 399–403.

    Article  PubMed  Google Scholar 

  6. Jackson, B. M., Gorman, J. H., Moainie, S. L., Guy, T. S., Narula, N., Narula, J., et al. (2002). Extension of borderzone myocardium in postinfarction dilated cardiomyopathy. Journal of the American College of Cardiology, 40(6), 1160–1167.

    Article  PubMed  Google Scholar 

  7. Jackson, B. M., Gorman, J. H., Salgo, I. S., Moainie, S. L., Plappert, T., St John-Sutton, M., et al. (2003). Border zone geometry increases wall stress after myocardial infarction: Contrast echocardiographic assessment. American Journal of Physiology. Heart and Circulatory Physiology, 284(2), H475–H479.

    PubMed  CAS  Google Scholar 

  8. Kramer, C. M., Lima, J. A. C., Reichek, N., Ferrari, V. A., Llaneras, M. R., Palmon, L. C., et al. (1993). Regional differences in function within noninfarcted myocardium during left-ventricular remodeling. Circulation, 88(3), 1279–1288.

    PubMed  CAS  Google Scholar 

  9. Lima, J. A. C., Becker, L. C., Melin, J. A., Lima, S., Kallman, C. A., Weisfeldt, M. L., et al. (1985). Impaired thickening of nonischemic myocardium during acute regional ischemia in the dog. Circulation, 71(5), 1048–1059.

    Article  PubMed  CAS  Google Scholar 

  10. Pilla, J. J., Blom, A. S., Gorman, J. H., 3rd, Brockman, D. J., Affuso, J., Parish, L. M., et al. (2005). Early postinfarction ventricular restraint improves borderzone wall thickening dynamics during remodeling. The Annals of Thoracic Surgery, 80(6), 2257–2262.

    Article  PubMed  Google Scholar 

  11. Gorman, R. C., Jackson, B. M., & Gorman, J. H. (2004). The potential role of ventricular compressive therapy. Surgical Clinics of North America, 84(1), 45-+.

    Article  PubMed  Google Scholar 

  12. Mann, D. L. (1999). Mechanisms and models in heart failure—A combinatorial approach. Circulation, 100(9), 999–1008.

    PubMed  CAS  Google Scholar 

  13. Sutton, M. G., & Sharpe, N. (2000). Left ventricular remodeling after myocardial infarction: Pathophysiology and therapy. Circulation, 101(25), 2981–2988.

    PubMed  CAS  Google Scholar 

  14. Blom, A. S., Pilla, J. J., Gorman, R. C., 3rd, Gorman, J. H., Mukherjee, R., Spinale, F. G., et al. (2005). Infarct size reduction and attenuation of global left ventricular remodeling with the CorCap cardiac support device following acute myocardial infarction in sheep. Heart Failure Reviews, 10(2), 125–139.

    Article  PubMed  Google Scholar 

  15. Enomoto, Y., Gorman, J. H., Moainie, S. L., Jackson, B. M., Parish, L. M., Plappert, T., et al. (2005). Early ventricular restraint after myocardial infarction: Extent of the wrap determines the outcome of remodeling. The Annals of Thoracic Surgery, 79(3), 881–887.

    Article  PubMed  Google Scholar 

  16. Kelley, S. T., Malekan, R., Gorman, J. H., 3rd, Jackson, B. M., Gorman, R. C., Suzuki, Y., et al. (1999). Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction. Circulation, 99(1), 135–142.

    PubMed  CAS  Google Scholar 

  17. Moainie, S. L., Guy, S., Gorman, J. H., Plappert, T., Jackson, B. M., St John-Sutton, M. G., et al. (2002). Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after postero-lateral infarction. The Annals of Thoracic Surgery, 74(2), 444–449.

    Article  PubMed  Google Scholar 

  18. Christman, K. L., Fok, H. H., Sievers, R. E., Fang, Q. H., & Lee, R. J. (2004). Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac function after myocardial infarction. Tissue Engineering, 10(3–4), 403–409.

    Article  PubMed  CAS  Google Scholar 

  19. Dai, W. D., Wold, L. E., Dow, J. S., & Kloner, R. A. (2005). Thickening of the infarcted wall by collagen injection improves left ventricular function in rats. Journal of the American College of Cardiology, 46(4), 714–719.

    Article  PubMed  CAS  Google Scholar 

  20. Davis, M. E., Hsieh, P. C. H., Takahashi, T., Song, Q., Zhang, S. G., Kamm, R. D., et al. (2006). Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 103(21), 8155–8160.

    Article  PubMed  CAS  Google Scholar 

  21. Dobner, S., Bezuidenhout, D., Govender, P., Zilla, P., & Davies, N. (2009). A synthetic non-degradable polyethylene glycol hydrogel retards adverse post-infarct left ventricular remodeling. Journal of Cardiac Failure, 15(7), 629–636.

    Article  PubMed  CAS  Google Scholar 

  22. Fujimoto, K. L., Ma, Z. W., Nelson, D. M., Hashizume, R., Guan, J. J., Tobita, K., et al. (2009). Synthesis, characterization and therapeutic efficacy of a biodegradable, thermoresponsive hydrogel designed for application in chronic infarcted myocardium. Biomaterials, 30(26), 4357–4368.

    Article  PubMed  CAS  Google Scholar 

  23. Huang, N. F., Yu, J., Sievers, R., Li, S., & Lee, R. J. (2005). Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Engineering, 11(11–12), 1860–1866.

    Article  PubMed  CAS  Google Scholar 

  24. Jiang, X. J., Wang, T., Li, X. Y., Wu, D. Q., Zheng, Z. B., Zhang, J. F., et al. (2009). Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction. Journal of Biomedical Materials Research. Part A, 90(2), 472–477.

    Article  PubMed  Google Scholar 

  25. Kofidis, T., Lebl, D. R., Martinez, E. C., Hoyt, G., Tanaka, M., & Robbins, R. C. (2005). Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury. Circulation, 112(9 Suppl), I173–I177.

    PubMed  Google Scholar 

  26. Landa, N., Miller, L., Feinberg, M. S., Holbova, R., Shachar, M., Freeman, I., et al. (2008). Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation, 117(11), 1388–1396.

    Article  PubMed  CAS  Google Scholar 

  27. Leor, J., Miller, L., Feinberg, M. S., Shachar, M., Landa, N., Holbova, R., et al. (2004). A novel injectable alginate scaffold promotes angiogenesis and preserves left ventricular geometry and function after extensive myocardial infarction in rat. Circulation, 110(17), 279.

    Google Scholar 

  28. Lu, W. N., Lu, S. H., Wang, H. B., Li, D. X., Duan, C. M., Liu, Z. Q., et al. (2009). Functional improvement of infarcted heart by co-injection of embryonic stem cells with temperature-responsive chitosan hydrogel. Tissue Engineering. Part A, 15(6), 1437–1447.

    Article  PubMed  CAS  Google Scholar 

  29. Mukherjee, R., Zavadzkas, J. A., Saunders, S. M., Mclean, J. E., Jeffords, L. B., Beck, C., et al. (2008). Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs. The Annals of Thoracic Surgery, 86(4), 1268–1276.

    Article  PubMed  Google Scholar 

  30. Singelyn, J. M., Dequach, J. A., Seif-Naraghi, S. B., Littlefield, R. B., Schup-Magoffin, P. J., & Christman, K. L. (2009). Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials, 30(29), 5409–5416.

    Article  PubMed  CAS  Google Scholar 

  31. Tsur-Gang, O., Ruvinov, E., Landa, N., Holbova, R., Feinberg, M. S., Leor, J., et al. (2009). The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials, 30(2), 189–195.

    Article  PubMed  CAS  Google Scholar 

  32. Wang, T., Wu, D. Q., Jiang, X. J., Zhang, X. Z., Li, X. Y., Zhang, J. F., et al. (2009). Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling. European Journal of Heart Failure, 11(1), 14–19.

    Article  PubMed  CAS  Google Scholar 

  33. Yoon, S. J., Fang, Y. H., Lim, C. H., Kim, B. S., Son, H. S., Park, Y., et al. (2009). Regeneration of ischemic heart using hyaluronic acid-based injectable hydrogel. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 91B, 163–171.

    Article  CAS  Google Scholar 

  34. Yu, J., Christman, K. L., Chin, E., Sievers, R. E., Saeed, M., & Lee, R. J. (2009). Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy. The Journal of Thoracic and Cardiovascular Surgery, 137(1), 180–187.

    Article  PubMed  Google Scholar 

  35. Wall, S. T., Walker, J. C., Healy, K. E., Ratcliffe, M. B., & Guccione, J. M. (2006). Theoretical impact of the injection of material into the myocardium: A finite element model simulation. Circulation, 114(24), 2627–2635.

    Article  PubMed  Google Scholar 

  36. Lee, K. Y., & Mooney, D. J. (2001). Hydrogels for tissue engineering. Chemical Reviews, 101(7), 1869–1879.

    Article  PubMed  CAS  Google Scholar 

  37. Minh, K. N., & Lee, D. S. (2010). Injectable biodegradable hydrogels. Macromolecular Bioscience, 10(6), 563–579.

    Article  Google Scholar 

  38. Yu, L., & Ding, J. D. (2008). Injectable hydrogels as unique biomedical materials. Chemical Society Reviews, 37(8), 1473–1481.

    Article  PubMed  CAS  Google Scholar 

  39. Nelson, D. M., Ma, Z., Fujimoto, K. L., Hashizume, R., & Wagner, W. R. (2011). Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges. Acta Biomaterialia, 7(1), 1–15.

    Article  PubMed  CAS  Google Scholar 

  40. Shapira, K., Dikovsky, D., Habib, M., Gepstein, L., & Seliktar, D. (2008). Hydrogels for cardiac tissue regeneration. Biomedical Materials and Engineering, 18(4–5), 309–314.

    PubMed  CAS  Google Scholar 

  41. Gupta, K. B., Ratcliffe, M. B., Fallert, M. A., Edmunds, L. H., Jr., & Bogen, D. K. (1994). Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation. Circulation, 89(5), 2315–2326.

    PubMed  CAS  Google Scholar 

  42. Holmes, J. W., Borg, T. K., & Covell, J. W. (2005). Structure and mechanics of healing myocardial infarcts. Annual Review of Biomedical Engineering, 7, 223–253.

    Article  PubMed  CAS  Google Scholar 

  43. Pfeffer, M. A., & Pfeffer, J. M. (1987). Ventricular enlargement and reduced survival after myocardial infarction. Circulation, 75(5 Pt 2), IV93–IV97.

    PubMed  CAS  Google Scholar 

  44. Batista, R. (1999). Partial left ventriculectomy—The Batista procedure. European Journal of Cardio-Thoracic Surgery, 15(Suppl 1), S12–S19. discussion S39–S43.

    Article  PubMed  Google Scholar 

  45. Starling, R. C., Jessup, M., Oh, J. K., Sabbah, H. N., Acker, M. A., Mann, D. L., et al. (2007). Sustained benefits of the corcap cardiac support device on left ventricular remodeling: Three year follow-up results from the acorn clinical trial. The Annals of Thoracic Surgery, 84(4), 1236–1242.

    Article  PubMed  Google Scholar 

  46. Sartipy, U., Albage, A., & Lindblom, D. (2005). The Dor procedure for left ventricular reconstruction. Ten-year clinical experience. European Journal of Cardio-Thoracic Surgery, 27(6), 1005–1010.

    Article  PubMed  Google Scholar 

  47. Klodell, C. T., Jr., Aranda, J. M., Jr., Mcgiffin, D. C., Rayburn, B. K., Sun, B., Abraham, W. T., et al. (2008). Worldwide surgical experience with the Paracor HeartNet cardiac restraint device. The Journal of Thoracic and Cardiovascular Surgery, 135(1), 188–195.

    Article  PubMed  Google Scholar 

  48. Christman, K. L., Vardanian, A. J., Fang, Q., Sievers, R. E., Fok, H. H., & Lee, R. J. (2004). Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. Journal of the American College of Cardiology, 44(3), 654–660.

    Article  PubMed  CAS  Google Scholar 

  49. Rowley, J. A., Madlambayan, G., & Mooney, D. J. (1999). Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials, 20(1), 45–53.

    Article  PubMed  CAS  Google Scholar 

  50. Leor, J., Tuvia, S., Guetta, V., Manczur, F., Castel, D., Willenz, U., et al. (2009). Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in swine. Journal of the American College of Cardiology, 54(11), 1014–1023.

    Article  PubMed  Google Scholar 

  51. Yu, J., Gu, Y., Du, K. T., Mihardja, S., Sievers, R. E., & Lee, R. J. (2009). The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model. Biomaterials, 30(5), 751–756.

    Article  PubMed  CAS  Google Scholar 

  52. Kim, I. Y., Seo, S. J., Moon, H. S., Yoo, M. K., Park, I. Y., Kim, B. C., et al. (2008). Chitosan and its derivatives for tissue engineering applications. Biotechnology Advances, 26(1), 1–21.

    Article  PubMed  CAS  Google Scholar 

  53. Ruel-Gariepy, E., Shive, M., Bichara, A., Berrada, M., Le Garrec, D., Chenite, A., et al. (2004). A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 53–63.

    Article  PubMed  CAS  Google Scholar 

  54. Chenite, A., Chaput, C., Wang, D., Combes, C., Buschmann, M. D., Hoemann, C. D., et al. (2000). Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials, 21(21), 2155–2161.

    Article  PubMed  CAS  Google Scholar 

  55. Chung, C., Beecham, M., Mauck, R. L., & Burdick, J. A. (2009). The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. Biomaterials, 30(26), 4287–4296.

    Article  PubMed  CAS  Google Scholar 

  56. Khetan, S., & Burdick, J. (2009). Cellular encapsulation in 3D hydrogels for tissue engineering. Journal of Visualized Experiments, 32. doi:10.3791/1590.

  57. Khetan, S., Chung, C., & Burdick, J. A. (2009). Tuning hydrogel properties for applications in tissue engineering. Conference Proceedings—IEEE Engineering in Medicine and Biology Society, 2009, 2094–2096.

    Google Scholar 

  58. Laurent, T. C., & Fraser, J. R. (1992). Hyaluronan. The FASEB Journal, 6(7), 2397–2404.

    PubMed  CAS  Google Scholar 

  59. Sahoo, S., Chung, C., Khetan, S., & Burdick, J. A. (2008). Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal structures. Biomacromolecules, 9(4), 1088–1092.

    Article  PubMed  CAS  Google Scholar 

  60. Toole, B. P. (2004). Hyaluronan: From extracellular glue to pericellular cue. Nature Reviews. Cancer, 4(7), 528–539.

    Article  PubMed  CAS  Google Scholar 

  61. Ifkovits, J. L., Tous, E., Minakawa, M., Morita, M., Robb, J. D., Koomalsingh, K. J., et al. (2010). Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proceedings of the National Academy of Sciences of the United States of America, 107(25), 11507–11512.

    Article  PubMed  CAS  Google Scholar 

  62. Kofidis, T., De Bruin, J. L., Hoyt, G., Lebl, D. R., Tanaka, M., Yamane, T., et al. (2004). Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. The Journal of Thoracic and Cardiovascular Surgery, 128(4), 571–578.

    PubMed  Google Scholar 

  63. Seif-Naraghi, S. B., Salvatore, M. A., Schup-Magoffin, P. J., Hu, D. P., & Christman, K. L. (2010). Design and characterization of an injectable pericardial matrix gel: A potentially autologous scaffold for cardiac tissue engineering. Tissue Engineering—Part A, 16(6), 2017–2027.

    Article  PubMed  CAS  Google Scholar 

  64. Wang, T., Jiang, X. J., Lin, T., Ren, S., Li, X. Y., Zhang, X. Z., et al. (2009). The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a supramolecular hydrogel. Biomaterials, 30(25), 4161–4167.

    Article  PubMed  CAS  Google Scholar 

  65. Dang, A. B., Guccione, J. M., Mishell, J. M., Zhang, P., Wallace, A. W., Gorman, R. C., et al. (2005). Akinetic myocardial infarcts must contain contracting myocytes: Finite-element model study. American Journal of Physiology. Heart and Circulatory Physiology, 288(4), H1844–H1850.

    Article  PubMed  CAS  Google Scholar 

  66. Pilla, J. J., Gorman, J. H., 3rd, & Gorman, R. C. (2009). Theoretic impact of infarct compliance on left ventricular function. The Annals of Thoracic Surgery, 87(3), 803–810.

    Article  PubMed  Google Scholar 

  67. Wenk, J. F., Wall, S. T., Peterson, R. C., Helgerson, S. L., Sabbah, H. N., Burger, M., et al. (2009). A method for automatically optimizing medical devices for treating heart failure: Designing polymeric injection patterns. Journal of Biomechanical Engineering, 131(12), 121011.

    Article  PubMed  Google Scholar 

  68. Sierra, D. H., Eberhardt, A. W., & Lemons, J. E. (2002). Failure characteristics of multiple-component fibrin-based adhesives. Journal of Biomedical Materials Research, 59(1), 1–11.

    Article  PubMed  CAS  Google Scholar 

  69. Martens, T. P., Godier, A. F., Parks, J. J., Wan, L. Q., Koeckert, M. S., Eng, G. M., et al. (2009). Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. Cell Transplantation, 18(3), 297–304.

    Article  PubMed  Google Scholar 

  70. Augst, A. D., Kong, H. J., & Mooney, D. J. (2006). Alginate hydrogels as biomaterials. Macromolecular Bioscience, 6(8), 623–633.

    Article  PubMed  CAS  Google Scholar 

  71. Ryan, L. P., Matsuzaki, K., Noma, M., Jackson, B. M., Eperjesi, T. J., Plappert, T. J., et al. (2009). Dermal filler injection: A novel approach for limiting infarct expansion. The Annals of Thoracic Surgery, 87(1), 148–155.

    Article  PubMed  Google Scholar 

  72. Anderson, J. M. (2001). Biological responses to materials. Annual Review of Materials Research, 31(20), 81–110.

    Article  CAS  Google Scholar 

  73. Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008). Foreign body reaction to biomaterials. Seminars in Immunology, 20(2), 86–100.

    Article  PubMed  CAS  Google Scholar 

  74. Badylak, S. F., Valentin, J. E., Ravindra, A. K., Mccabe, G. P., & Stewart-Akers, A. M. (2008). Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Engineering. Part A, 14(11), 1835–1842.

    Article  PubMed  CAS  Google Scholar 

  75. Brown, B. N., Valentin, J. E., Stewart-Akers, A. M., Mccabe, G. P., & Badylak, S. F. (2009). Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials, 30(8), 1482–1491.

    Article  PubMed  CAS  Google Scholar 

  76. Rodriguez, A., Meyerson, H., & Anderson, J. M. (2009). Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites. Journal of Biomedical Materials Research. Part A, 89(1), 152–159.

    PubMed  Google Scholar 

  77. Ziats, N. P., Miller, K. M., & Anderson, J. M. (1988). In vitro and in vivo interactions of cells with biomaterials. Biomaterials, 9(1), 5–13.

    Article  PubMed  CAS  Google Scholar 

  78. Epstein, S. E., Fuchs, S., Zhou, Y. F., Baffour, R., & Kornowski, R. (2001). Therapeutic interventions for enhancing collateral development by administration of growth factors: Basic principles, early results and potential hazards. Cardiovascular Research, 49(3), 532–542.

    Article  PubMed  CAS  Google Scholar 

  79. Langer, R., & Folkman, J. (1976). Polymers for sustained-release of proteins and other macromolecules. Nature, 263(5580), 797–800.

    Article  PubMed  CAS  Google Scholar 

  80. Gombotz, W. R., & Pettit, D. K. (1995). Biodegradable polymers for protein and peptide drug-delivery. Bioconjugate Chemistry, 6(4), 332–351.

    Article  PubMed  CAS  Google Scholar 

  81. Ruvinov, E., Leor, J., & Cohen, S. (2011). The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials, 32(2), 565–578.

    Article  PubMed  CAS  Google Scholar 

  82. Hsieh, P. C. H., Davis, M. E., Gannon, J., Macgillivray, C., & Lee, R. T. (2006). Controlled delivery of PDGF-BB for myocardial protection using injectable self-assembling peptide nanofibers. Journal of Clinical Investigation, 116(1), 237–248.

    Article  PubMed  CAS  Google Scholar 

  83. Hsieh, P. C. H., Macgillivray, C., Gannon, J., Cruz, F. U., & Lee, R. T. (2006). Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity. Circulation, 114(7), 637–644.

    Article  PubMed  CAS  Google Scholar 

  84. Lee, J., Tan, C. Y., Lee, S. K., Kim, Y. H., & Lee, K. Y. (2009). Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarction. Journal of Controlled Release, 137(3–4), 196–202.

    Article  PubMed  CAS  Google Scholar 

  85. Wang, H. B., Zhang, X. L., Li, Y. M., Ma, Y. T., Zhang, Y., Liu, Z. G., et al. (2010). Improved myocardial performance in infarcted rat heart by co-injection of basic fibroblast growth factor with temperature-responsive chitosan hydrogel. The Journal of Heart and Lung Transplantation, 29(8), 881–887.

    Article  PubMed  CAS  Google Scholar 

  86. Sakakibara, Y., Yamamoto, M., Nishimura, K., Nishina, T., Miwa, S., Handa, N., et al. (2000). Prevascularization using gelatin microsphere containing basic-fibroblast growth factor enhances the benefits of cardiomyocytes transplantation in rats with ischemic cardiomyopathy. Circulation, 102(18), 650.

    Google Scholar 

  87. Yamamoto, T., Suto, N., Okubo, T., Mikuniya, A., Hanada, H., Yagihashi, S., et al. (2001). Intramyocardial delivery of basic fibroblast growth factor-impregnated gelatin hydrogel microspheres enhances collateral circulation to infarcted canine myocardium. Japanese Circulation Journal-English Edition, 65(5), 439–444.

    Article  CAS  Google Scholar 

  88. Iwakura, A., Fujita, M., Kataoka, K., Tambara, K., Sakakibara, Y., Komeda, M., et al. (2003). Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model. Heart and Vessels, 18(2), 93–99.

    Article  PubMed  Google Scholar 

  89. Liu, Y., Sun, L. J., Huan, Y., Zhao, H. T., & Deng, J. L. (2006). Effects of basic fibroblast growth factor microspheres on angiogenesis in ischemic myocardium and cardiac function: Analysis with dobutamine cardiovascular magnetic resonance tagging. European Journal of Cardio-Thoracic Surgery, 30(1), 103–107.

    Article  PubMed  CAS  Google Scholar 

  90. Fujita, M., Ishihara, M., Morimoto, Y., Simizu, M., Saito, Y., Yura, H., et al. (2005). Efficacy of photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2 in a rabbit model of chronic myocardial infarction. Journal of Surgical Research, 126(1), 27–33.

    Article  PubMed  CAS  Google Scholar 

  91. Yancopoulos, G. D., Davis, S., Gale, N. W., Rudge, J. S., Wiegand, S. J., & Holash, J. (2000). Vascular-specific growth factors and blood vessel formation. Nature, 407(6801), 242–248.

    Article  PubMed  CAS  Google Scholar 

  92. Hao, X. J., Silva, E. A., Mansson-Broberg, A., Grinnemo, K. H., Siddiqui, A. J., Dellgren, G., et al. (2007). Angiogenic effects of sequential release of VEGF-A(165) and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovascular Research, 75(1), 178–185.

    Article  PubMed  CAS  Google Scholar 

  93. Wu, J., Zeng, F. Q., Huang, X. P., Chung, J. C. Y., Konecny, F., Weisel, R. D., et al. (2011). Infarct stabilization and cardiac repair with a VEGF-conjugated, injectable hydrogel. Biomaterials, 32(2), 579–586.

    Article  PubMed  CAS  Google Scholar 

  94. Kwon, J. S., Park, I. K., Cho, A. S., Shin, S. M., Hong, M. H., Jeong, S. Y., et al. (2009). Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model. Journal of Controlled Release, 138(2), 168–176.

    Article  PubMed  CAS  Google Scholar 

  95. Christman, K. L., Fang, Q. Z., Yee, M. S., Johnson, K. R., Sievers, R. E., & Lee, R. J. (2005). Enhanced neovasculature formation in ischemic myocardium following delivery of pleiotrophin plasmid in a biopolymer. Biomaterials, 26(10), 1139–1144.

    Article  PubMed  CAS  Google Scholar 

  96. Bonadio, J., Smiley, E., Patil, P., & Goldstein, S. (1999). Localized, direct plasmid gene delivery in vivo: Prolonged therapy results in reproducible tissue regeneration. Nature Medicine, 5(7), 753–759.

    Article  PubMed  CAS  Google Scholar 

  97. Shea, L. D., Smiley, E., Bonadio, J., & Mooney, D. J. (1999). DNA delivery from polymer matrices for tissue engineering. Nature Biotechnology, 17(6), 551–554.

    Article  PubMed  CAS  Google Scholar 

  98. Segers, V. F., Tokunou, T., Higgins, L. J., Macgillivray, C., Gannon, J., & Lee, R. T. (2007). Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruitment after myocardial infarction. Circulation, 116(15), 1683–1692.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jason A. Burdick.

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Elena Tous and Brendan Purcell contributed equally.

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Tous, E., Purcell, B., Ifkovits, J.L. et al. Injectable Acellular Hydrogels for Cardiac Repair. J. of Cardiovasc. Trans. Res. 4, 528–542 (2011). https://doi.org/10.1007/s12265-011-9291-1

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  • DOI: https://doi.org/10.1007/s12265-011-9291-1

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