Drug Delivery and Translational Research

, Volume 9, Issue 5, pp 920–934 | Cite as

Collagen biomaterial for the treatment of myocardial infarction: an update on cardiac tissue engineering and myocardial regeneration

  • Wei-qiang Wu
  • Song Peng
  • Zhi-yuan SongEmail author
  • Shu LinEmail author
Review Article


Myocardial infarction (MI) remains one of the leading cause of mortality over the world. However, current treatments are more palliative than curative, which only stall the progression of the disease, but not reverse the disease. While stem cells or bioactive molecules therapy is promising, the limited survival and engraftment of bioactive agent due to a hostile environment is a bottleneck for MI treatment. In order to maximize the utility of stem cells and bioactive molecules for myocardial repair and regeneration, various types of biomaterials have been developed. Among them, collagen-based biomaterial is widely utilized for cardiac tissue engineering and regeneration due to its optimal physical and chemical properties. In this review, we summarize the properties of collagen-based biomaterial. Then, we discuss collagen-based biomaterial currently being applied to treat MI alone, or together with stem cells and/or bioactive molecules. Finally, the delivery system of collagen-based biomaterial will also be discussed.


Myocardial infarction Collagen Biomaterials Stem cells Delivery systems 



This work was supported by the National Natural Science Foundation of China (Nos. 81670402 and 81570395).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348(20):2007–18. Scholar
  2. 2.
    Baig MK, Mahon N, McKenna WJ, Caforio ALP, Bonow RO, Francis GS, et al. The pathophysiology of advanced heart failure. Am Heart J. 1998;135(6):S216–30. Scholar
  3. 3.
    Rong S, Wang X, Zhang C, Song Z, Cui L, He X, et al. Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model. Plos One. 2017;12(5):e175807. Scholar
  4. 4.
    Kurazumi H, Fujita A, Nakamura T, Suzuki R, Takahashi M, Shirasawa B, et al. Short- and long-term outcomes of intramyocardial implantation of autologous bone marrow-derived cells for the treatment of ischaemic heart disease. Interact Cardiovasc Th. 2016;24(3):w412. Scholar
  5. 5.
    Sun J, Wei T, Bai S, Zhao H, Liu X, Yu J, et al. Calcium-sensing receptor-mediated mitogen-activated protein kinase pathway improves the status of transplanted mouse embryonic stem cells in rats with acute myocardial infarction. Mol Cell Biochem. 2017;431(1–2):151–60. Scholar
  6. 6.
    Rabbani S, Soleimani M, Imani M, Sahebjam M, Ghiaseddin A, Nassiri SM, et al. Regenerating heart using a novel compound and human wharton jelly mesenchymal stem cells. Arch Med Res. 2017;48(3):228–37. Scholar
  7. 7.
    Wang J, Xiang B, Deng J, Lin H, Freed DH, Arora RC, et al. Hypoxia enhances the therapeutic potential of superparamagnetic iron oxide-labeled adipose-derived stem cells for myocardial infarction. J Huazhong Univ Sci Technol [Med Sci]. 2017;37(4):516–22. Scholar
  8. 8.
    Song F, Hua F, Li H, Zhou X, Yan L, Yang Q, et al. Cardiac stem cell transplantation with 2,3,5,4′-tetrahydroxystilbehe-2-O-β-d-glucoside improves cardiac function in rat myocardial infarction model. Life Sci. 2016;158:37–45. Scholar
  9. 9.
    Rojas SV, Kensah G, Rotaermel A, Baraki H, Kutschka I, Zweigerdt R, et al. Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction. Plos One. 2017;12(5):e173222. Scholar
  10. 10.
    Reinecke H, Murry CE. Taking the death toll after cardiomyocyte grafting: a reminder of the importance of quantitative biology. J Mol Cell Cardiol. 2002;34(3):251–3. Scholar
  11. 11.
    Korf-Klingebiel M, Kempf T, Sauer T, Brinkmann E, Fischer P, Meyer GP, et al. Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction. Eur Heart J. 2008;29(23):2851–8. Scholar
  12. 12.
    Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661–9. Scholar
  13. 13.
    Shafiq M, Jung Y, Kim SH. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair. Biomaterials. 2016;90:85–115. Scholar
  14. 14.
    Bhattacharjee A, Bansal M. Collagen structure: the madras triple helix and the current scenario. IUBMB Life. 2005;57(3):161–72. Scholar
  15. 15.
    Puxkandl R, Zizak I, Paris O, Keckes J, Tesch W, Bernstorff S, et al. Viscoelastic properties of collagen: synchrotron radiation investigations and structural model. Philos Trans R Soc B Biol Sci. 2002;357(1418):191–7. Scholar
  16. 16.
    Abou Neel EA, Bozec L, Knowles JC, Syed O, Mudera V, Day R, et al. Collagen—emerging collagen based therapies hit the patient. Adv Drug Deliver Rev. 2013;65(4):429–56. Scholar
  17. 17.
    Gelse K. Collagens—structure, function, and biosynthesis. Adv Drug Deliver Rev. 2003;55(12):1531–46. Scholar
  18. 18.
    Venugopal JR, Prabhakaran MP, Mukherjee S, Ravichandran R, Dan K, Ramakrishna S. Biomaterial strategies for alleviation of myocardial infarction. J R Soc Interface. 2011;9(66):1–19. Scholar
  19. 19.
    Jayarama Reddy Venugopal MPP, Shayanti Mukherjee RR, Ramakrishna KDAS. Biomaterial strategies for alleviation of myocardial infarction. J R Soc Interface. 2012;9:1–19. Scholar
  20. 20.
    Gazoti DC, Mesiano ML, Rodrigues DSR. Age related changes of the collagen network of the human heart. Mech Ageing Dev. 2001;122(10):1049–58.Google Scholar
  21. 21.
    Bishop JE. Regulation of cardiovascular collagen deposition by mechanical forces. Mol Med Today. 1998;4(2):69–75. Scholar
  22. 22.
    Valiente-Alandi I, Schafer AE, Blaxall BC. Extracellular matrix-mediated cellular communication in the heart. J Mol Cell Cardiol. 2016;91:228–37. Scholar
  23. 23.
    Haraguchi Y, Shimizu T, Yamato M, Okano T. Concise review: cell therapy and tissue engineering for cardiovascular disease. Stem Cell Transl Med. 2012;1(2):136–41. Scholar
  24. 24.
    Sherrell PC, Cieślar-Pobuda A, Ejneby MS, Sammalisto L, Gelmi A, de Muinck E, et al. Rational design of a conductive collagen heart patch. Macromol Biosci. 2017;17(7):1600446. Scholar
  25. 25.
    Hein S. The extracellular matrix in normal and diseased myocardium. J Nucl Cardiol. 2001;8(2):188–96. Scholar
  26. 26.
    Nogami K, Kusachi S, Nunoyama H, Kondo J, Endo C, Yamamoto K, et al. Extracellular matrix components in dilated cardiomyopathy. immunohistochemical study of endomyocardial biopsy specimens. Jpn Heart J. 1996;37(4):483–94. Scholar
  27. 27.
    Jane-Lise S, Corda S, Chassagne C, Rappaport L. The extracellular matrix and the cytoskeleton in heart hypertrophy and failure. Heart Fail Rev. 2000;5(3):239–50. Scholar
  28. 28.
    Ahmadi A, Mc-Neill B, Vulesevic B, Kordos M, Mesana L, Thorn S, et al. The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium. Biomaterials. 2014;35(17):4749–58. Scholar
  29. 29.
    Perea-Gil I, Prat-Vidal C, Bayes-Genis A. In vivo experience with natural scaffolds for myocardial infarction: the times they are a-changin’. Stem Cell Res Ther. 2015;6(1).
  30. 30.
    Goldsmith EC, Borg TK. The dynamic interaction of the extracellular matrix in cardiac remodeling. J Card Fail. 2002;8(6):S314–8. Scholar
  31. 31.
    Herpel E, Pritsch M, Koch A, Dengler TJ, Schirmacher P, Schnabel PA. Interstitial fibrosis in the heart: differences in extracellular matrix proteins and matrix metalloproteinases in end-stage dilated, ischaemic and valvular cardiomyopathy. Histopathology. 2006;48(6):736–47. Scholar
  32. 32.
    Woodiwiss AJ, Tsotetsi OJ, Sprott S, Lancaster EJ, Mela T, Chung ES, et al. Reduction in myocardial collagen cross-linking parallels left ventricular dilatation in rat models of systolic chamber dysfunction. Circulation. 2001;103(1):155–60. Scholar
  33. 33.
    Olivetti G, Capasso JM, Sonnenblick EH, Anversa P. Side-to-side slippage of myocytes participates in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res. 1990;67(1):23–34. Scholar
  34. 34.
    Vunjak-Novakovic G, Lui KO, Tandon N, Chien KR. Bioengineering heart muscle: a paradigm for regenerative medicine. Annu Rev Biomed Eng. 2011;13(1):245–67. Scholar
  35. 35.
    Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Therapeut. 2005;105(2):151–63. Scholar
  36. 36.
    Finosh GT, Jayabalan M. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges. Biomatter. 2012;2(1):1–14. Scholar
  37. 37.
    Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53. Scholar
  38. 38.
    Blackburn NJR, Sofrenovic T, Kuraitis D, Ahmadi A, McNeill B, Deng C, et al. Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction. Biomaterials. 2015;39:182–92. Scholar
  39. 39.
    Boccafoschi F, Habermehl J, Vesentini S, Mantovani D. Biological performances of collagen-based scaffolds for vascular tissue engineering. Biomaterials. 2005;26(35):7410–7. Scholar
  40. 40.
    Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials. 2006;27(18):3413–31. Scholar
  41. 41.
    Goissis G, Marcantonio EJ, Marcantonio RA, Lia RC, Cancian DC, de Carvalho WM. Biocompatibility studies of anionic collagen membranes with different degree of glutaraldehyde cross-linking. Biomaterials. 1999;20(1):27–34.Google Scholar
  42. 42.
    Ahmadi AL, Thorn S, Alarcon EI, Kordos M, Padavan DT, Hadizad T, et al. PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction. Biomaterials. 2015;49:18–26. Scholar
  43. 43.
    Neuta PA, Rojas DM, Agredo W, Gutierrez JO. Evaluation of the repairing effect of collagen type I and MaxGel on the infarcted myocardium in an animal model. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:3529–32. Scholar
  44. 44.
    Serpooshan V, Zhao M, Metzler SA, Wei K, Shah PB, Wang A, et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials. 2013;34(36):9048–55. Scholar
  45. 45.
    Huang NF, Yu J, Sievers R, Li S, Lee RJ. Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng. 2005;11(11–12):1860–6. Scholar
  46. 46.
    Cortes-Morichetti M, Frati G, Schussler O, Van Huyen JD, Lauret E, Genovese JA, et al. Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration. Tissue Eng. 2007;13(11):2681–7. Scholar
  47. 47.
    Xiang Z, Liao R, Kelly MS, Spector M. Collagen-GAG scaffolds grafted onto myocardial infarcts in a rat model: a delivery vehicle for mesenchymal stem cells. Tissue Eng. 2006;12(9):2467–78. Scholar
  48. 48.
    Gaballa MA, Sunkomat JNE, Thai H, Morkin E, Ewy G, Goldman S. Grafting an acellular 3-dimensional collagen scaffold onto a non-transmural infarcted myocardium induces neo-angiogenesis and reduces cardiac remodeling. J Heart Lung Transplant. 2006;25(8):946–54. Scholar
  49. 49.
    Araña M, Peña E, Abizanda G, Cilla M, Ochoa I, Gavira JJ, et al. Preparation and characterization of collagen-based ADSC-carrier sheets for cardiovascular application. Acta Biomater. 2013;9(4):6075–83. Scholar
  50. 50.
    Maureira P, Marie PY, Yu F, Poussier S, Liu Y, Groubatch F, et al. Repairing chronic myocardial infarction with autologous mesenchymal stem cells engineered tissue in rat promotes angiogenesis and limits ventricular remodeling. J Biomed Sci. 2012;19:93. Scholar
  51. 51.
    Ruping Q, Kuken B, Huang Y, Sun J, Azhati A. Effection of myocardial cell/collagen compound on ventricular electrophysiology in rats with myocardial infarction. Eur Rev Med Pharmacol Sci. 2016;20(11):2357–62.Google Scholar
  52. 52.
    Araña M, Gavira JJ, Peña E, González A, Abizanda G, Cilla M, et al. Epicardial delivery of collagen patches with adipose-derived stem cells in rat and mini pig models of chronic myocardial infarction. Biomaterials. 2014;35(1):143–51. Scholar
  53. 53.
    Chachques JC, Trainini JC, Lago N, Masoli OH, Barisani JL, Cortes-Morichetti M, et al. Myocardial assistance by grafting a new bioartificial upgraded myocardium (MAGNUM clinical trial): one year follow-up. Cell Transplant. 2007;16(9):927–34.Google Scholar
  54. 54.
    Chachques JC, Trainini JC, Lago N, Cortes-Morichetti M, Schussler O, Carpentier A. Myocardial assistance by grafting a new bioartificial upgraded myocardium (MAGNUM Trial): clinical feasibility study. Ann Thorac Surg. 2008;85(3):901–8. Scholar
  55. 55.
    Hamdi H, Planat-Benard V, Bel A, Neamatalla H, Saccenti L, Calderon D, et al. Long-term functional benefits of epicardial patches as cell carriers. Cell Transplant. 2014;23(1):87–96. Scholar
  56. 56.
    Danoviz ME, Nakamuta JS, Marques FL, Dos SL, Alvarenga EC, Dos SA, et al. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention. Plos One. 2010;5(8):e12077. Scholar
  57. 57.
    Shi C, Li Q, Zhao Y, Chen W, Chen B, Xiao Z, et al. Stem-cell-capturing collagen scaffold promotes cardiac tissue regeneration. Biomaterials. 2011;32(10):2508–15. Scholar
  58. 58.
    Shafy A, Fink T, Zachar V, Lila N, Carpentier A, Chachques JC. Development of cardiac support bioprostheses for ventricular restoration and myocardial regeneration. Eur J Cardio-Thorac. 2013;43(6):1211–9. Scholar
  59. 59.
    Holladay CA, Duffy AM, Chen X, Sefton MV, O Brien TD, Pandit AS. Recovery of cardiac function mediated by MSC and interleukin-10 plasmid functionalised scaffold. Biomaterials. 2012;33(5):1303–14. Scholar
  60. 60.
    Dai W, Wold LE, Dow JS, Kloner RA. Thickening of the infarcted wall by collagen injection improves left ventricular function in rats. J Am Coll Cardiol. 2005;46(4):714–9. Scholar
  61. 61.
    Gao J, Liu J, Gao Y, Wang C, Zhao Y, Chen B, et al. A myocardial patch made of collagen membranes loaded with collagen-binding human vascular endothelial growth factor accelerates healing of the injured rabbit heart. Tissue Eng A. 2011;17(21–22):2739–47. Scholar
  62. 62.
    Kouris NA, Squirrell JM, Jung JP, Pehlke CA, Hacker T, Eliceiri KW, et al. A nondenatured, noncrosslinked collagen matrix to deliver stem cells to the heart. Regen Med. 2011;6(5):569–82. Scholar
  63. 63.
    Dai W, Hale SL, Kay GL, Jyrala AJ, Kloner RA. Delivering stem cells to the heart in a collagen matrix reduces relocation of cells to other organs as assessed by nanoparticle technology. Regen Med. 2009;4(3):387–95. Scholar
  64. 64.
    Kutschka I. Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. Circulation. 2006;114(1_suppl):167–73. Scholar
  65. 65.
    Kutschka I, Chen IY, Kofidis T, von Degenfeld G, Sheikh AY, Hendry SL, et al. In vivo optical bioluminescence imaging of collagen-supported cardiac cell grafts. J Heart Lung Transplant. 2007;26(3):273–80. Scholar
  66. 66.
    Mokashi SA, Guan J, Wang D, Tchantchaleishvili V, Brigham M, Lipsitz S, et al. Preventing cardiac remodeling: the combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia. J Thorac Cardiovasc Surg. 2010;140(6):1374–80. Scholar
  67. 67.
    Xu G, Wang X, Deng C, Teng X, Suuronen EJ, Shen Z, et al. Injectable biodegradable hybrid hydrogels based on thiolated collagen and oligo (acryloyl carbonate)–poly (ethylene glycol)–oligo (acryloyl carbonate) copolymer for functional cardiac regeneration. Acta Biomater. 2015;15:55–64. Scholar
  68. 68.
    Ahmadi A, Vulesevic B, Blackburn NJR, Ruel JJM, Suuronen EJ. A collagen-chitosan injectable hydrogel improves cardiac remodeling in a mouse model of myocardial infarction. J Biomater Tiss Eng. 2014;4(11):886–94. Scholar
  69. 69.
    Reis LA, LLY C, Wu J, Feric N, Laschinger C, Momen A, et al. Hydrogels with integrin-binding angiopoietin-1–derived peptide, QHREDGS, for treatment of acute myocardial infarction. Circ Heart Fail. 2015;8(2):333–41. Scholar
  70. 70.
    Chiu LL, Reis LA, Momen A, Radisic M. Controlled release of thymosin β4 from injected collagen–chitosan hydrogels promotes angiogenesis and prevents tissue loss after myocardial infarction. Regen Med. 2012;7(4):523–33. Scholar
  71. 71.
    Radhakrishnan J, Krishnan UM, Sethuraman S. Hydrogel based injectable scaffolds for cardiac tissue regeneration. Biotechnol Adv. 2014;32(2):449–61. Scholar
  72. 72.
    Segers VFM, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008;451(7181):937–42. Scholar
  73. 73.
    Wang H, Zhou J, Liu Z, Wang C. Injectable cardiac tissue engineering for the treatment of myocardial infarction. J Cell Mol Med. 2010.
  74. 74.
    Robey TE, Saiget MK, Reinecke H, Murry CE. Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol. 2008;45(4):567–81. Scholar
  75. 75.
    Roche ET, Hastings CL, Lewin SA, Shvartsman DE, Brudno Y, Vasilyev NV, et al. Comparison of biomaterial delivery vehicles for improving acute retention of stem cells in the infarcted heart. Biomaterials. 2014;35(25):6850–8. Scholar
  76. 76.
    Araña M, Gavira JJ, Peña E, González A, Abizanda G, Cilla M, et al. Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction. Biomaterials. 2014;35(1):143–51. Scholar
  77. 77.
    Amado LC, Saliaris AP, Schuleri KH, St. John M, Xie JS, Cattaneo S, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci. 2005;102(32):11474–9. Scholar
  78. 78.
    Aggarwal S. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–22. Scholar
  79. 79.
    Wollert KC. Clinical applications of stem cells for the heart. Circ Res. 2005;96(2):151–63. Scholar
  80. 80.
    Bonafe F, Govoni M, Giordano E, Caldarera CM, Guarnieri C, Muscari C. Hyaluronan and cardiac regeneration. J Biomed Sci. 2014;21:100. Scholar
  81. 81.
    Young PP, Vaughan DE, Hatzopoulos AK. Biologic properties of endothelial progenitor cells and their potential for cell therapy. Prog Cardiovasc Dis. 2007;49(6):421–9. Scholar
  82. 82.
    Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001;107(11):1395–402. Scholar
  83. 83.
    Nagata H, Ii M, Kohbayashi E, Hoshiga M, Hanafusa T, Asahi M. Cardiac adipose-derived stem cells exhibit high differentiation potential to cardiovascular cells in C57BL/6 mice. Stem Cells Transl Med. 2016;5(2):141–51. Scholar
  84. 84.
    Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ. Engineering cardiac tissue in vivo from human adipose-derived stem cells. Biomaterials. 2010;31(8):2236–42. Scholar
  85. 85.
    Ma T, Sun J, Zhao Z, Lei W, Chen Y, Wang X, et al. A brief review: adipose-derived stem cells and their therapeutic potential in cardiovascular diseases. Stem Cell Res Ther. 2017;8(1).
  86. 86.
    Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, et al. Cozzarelli prize winner: robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci. 2012;109(27):E1848–57. Scholar
  87. 87.
    Zhao S, Xu Z, Wang H, Reese BE, Gushchina LV, Jiang M, et al. Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction. Nat Commun. 2016;7:13306. Scholar
  88. 88.
    Wang L, Zhang X, Xu C, Liu H, Qin J. Human induced pluripotent stem cell-derived cardiac tissue on a thin collagen membrane with natural microstructures. Biomater Sci. 2016;4(11):1655–62. Scholar
  89. 89.
    Di Spigna G, Iannone M, Ladogana P, Salzano S, Ventre M, Covelli B, et al. Human cardiac multipotent adult stem cells in 3D matrix: new approach of tissue engineering in cardiac regeneration post-infarction. J Biol Regul Homeost Agents. 2017;31(4):911–21.Google Scholar
  90. 90.
    Fernandes S, Chong J, Paige SL, Iwata M, Torok-Storb B, Keller G, et al. Comparison of human embryonic stem cell-derived cardiomyocytes, cardiovascular progenitors, and bone marrow mononuclear cells for cardiac repair. Stem Cell Rep. 2015;5(5):753–62. Scholar
  91. 91.
    Ling L, Gu S, Cheng Y. Resveratrol activates endogenous cardiac stem cells and improves myocardial regeneration following acute myocardial infarction. Mol Med Rep. 2017;15(3):1188–94. Scholar
  92. 92.
    Simpson D, Liu H, Fan TM, Nerem R, Dudley SC. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells. 2007;25(9):2350–7. Scholar
  93. 93.
    Malliaras K, Marban E. Cardiac cell therapy: where we’ve been, where we are, and where we should be headed. Br Med Bull. 2011;98(1):161–85. Scholar
  94. 94.
    Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation. 2000;102(8):898–901. Scholar
  95. 95.
    Nagai N, Kumasaka N, Kawashima T, Kaji H, Nishizawa M, Abe T. Preparation and characterization of collagen microspheres for sustained release of VEGF. J Mater Sci Mater Med. 2010;21(6):1891–8. Scholar
  96. 96.
    Bui QT, Gertz ZM, Wilensky RL. Intracoronary delivery of bone-marrow-derived stem cells. Stem Cell Res Ther. 2010;1(4):29. Scholar
  97. 97.
    Rufaihah AJ, Seliktar D. Hydrogels for therapeutic cardiovascular angiogenesis. Adv Drug Deliver Rev. 2016;96:31–9. Scholar
  98. 98.
    Kofidis T, de Bruin JL, Hoyt G, Lebl DR, Tanaka M, Yamane T, et al. Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. J Thorac Cardiovasc Surg. 2004;128(4):571–8. Scholar
  99. 99.
    Johnson TD, Christman KL. Injectable hydrogel therapies and their delivery strategies for treating myocardial infarction. Expert Opin Drug Del. 2012;10(1):59–72. Scholar
  100. 100.
    Dib N, Campbell A, Jacoby DB, Zawadzka A, Ratliff J, Miedzybrocki BM, et al. Safety and feasibility of percutaneous autologous skeletal myoblast transplantation in the coil-infarcted swine myocardium. J Pharmacol Toxicol Methods. 2006;54(1):71–7. Scholar
  101. 101.
    Sepantafar M, Maheronnaghsh R, Mohammadi H, Rajabi-Zeleti S, Annabi N, Aghdami N, et al. Stem cells and injectable hydrogels: synergistic therapeutics in myocardial repair. Biotechnol Adv. 2016;34(4):362–79. Scholar
  102. 102.
    Kofidis T, Lebl DR, Martinez EC, Hoyt G, Tanaka M, Robbins RC. Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury. Circulation. 2005;112(9 Suppl):I173–7. Scholar
  103. 103.
    Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35–43. Scholar
  104. 104.
    Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–21. Scholar
  105. 105.
    Barandon L, Couffinhal T, Dufourcq P, Alzieu P, Daret D, Deville C, et al. Repair of myocardial infarction by epicardial deposition of bone marrow cell-coated muscle patch in a murine model. Ann Thorac Surg. 2004;78(4):1409–17. Scholar
  106. 106.
    Ungerleider JL, Christman KL. Concise review: injectable biomaterials for the treatment of myocardial infarction and peripheral artery disease: translational challenges and progress. Stem Cells Transl Med. 2014;3(9):1090–9. Scholar

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© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Department of Cardiology, Southwest HospitalThird Military Medical University (Army Medical University)ChongqingChina
  2. 2.School of MedicineUniversity of Wollongong and Illawarra Health and Medical Research InstituteKeiravilleAustralia

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