Progress in hydrogel implantation in treatment of heart failure_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

KONG Pengxu ,  PAN Xiangbin

Structural Heart Disease Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, P. R. China;

Corresponding author：

PAN Xiangbin, Email: panxiangbin@fuwaihospital.org

Keywords：

Hydrogel; heart failure; treatment; tissue engineering; clinical trial; review

DOI：

10.7507/1007-4848.202011085

Video：

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Heart failure affects quality of life and life expectancy of tens of millions of individuals. There are no available economic and effective treatments for end-stage heart failure. Hydrogels are novel tissue engineering materials, which have the potential to ameliorate myocardium remodeling, increase cardiac output, improve quality of life and prolong life span by implantation into myocardium. The preclinical experiments and clinical trials have greatly explored the function of hydrogels in heart failure. In this review, we summarized the approaches of implantation, mechanism and clinical outcomes of the hydrogels.

Citation： KONG Pengxu, PAN Xiangbin. Progress in hydrogel implantation in treatment of heart failure. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(4): 502-507. doi: 10.7507/1007-4848.202011085 Copy

1.	Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J, 2016, 37(27): 2129-2200.
2.	Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart, 2007, 93(9): 1137-1146.
3.	Redfield MM, Jacobsen SJ, Burnett JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: Appreciating the scope of the heart failure epidemic. JAMA, 2003, 289(2): 194-202.
4.	Bleumink GS, Knetsch AM, Sturkenboom MC, et al. Quantifying the heart failure epidemic: Prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J, 2004, 25(18): 1614-1619.
5.	Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol, 2016, 13(6): 368-378.
6.	中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2019概要. 中国循环杂志, 2020, 35(9): 833-854.
7.	Hao G, Wang X, Chen Z, et al. Prevalence of heart failure and left ventricular dysfunction in China: The China hypertension survey, 2012-2015. Eur J Heart Fail, 2019, 21(11): 1329-1337.
8.	Maggioni AP, Dahlström U, Filippatos G, et al. EURObservational Research Programme: Regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail, 2013, 15(7): 808-817.
9.	Shah KS, Xu H, Matsouaka RA, et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol, 2017, 70(20): 2476-2486.
10.	Gauvin R, Parenteau-Bareil R, Dokmeci MR, et al. Hydrogels and microtechnologies for engineering the cellular microenvironment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2012, 4(3): 235-246.
11.	Zhu J, Marchant RE. Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices, 2011, 8(5): 607-626.
12.	Batista RA, Otoni CG, Espitia PJP. Chapter 3—Fundamentals of chitosan-based hydrogels: Elaboration and characterization techniques. Holban A, Grumezescu AM, eds. Materials for Biomedical Engineering. The Netherlands: Elsevier, 2019. 61-81.
13.	Lee LC, Wall ST, Klepach D, et al. Algisyl-LVR^TM with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart. Int J Cardiol, 2013, 168(3): 2022-2028.
14.	Sabbah HN, Wang M, Gupta RC, et al. Augmentation of left ventricular wall thickness with alginate hydrogel implants improves left ventricular function and prevents progressive remodeling in dogs with chronic heart failure. JACC Heart Fail, 2013, 1(3): 252-258.
15.	Singelyn JM, DeQuach JA, Seif-Naraghi SB, et al. Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials, 2009, 30(29): 5409-5416.
16.	Traverse JH, Henry TD, Dib N, et al. First-in-man study of a cardiac extracellular matrix hydrogel in early and late myocardial infarction patients. JACC Basic Transl Sci, 2019, 4(6): 659-669.
17.	Leor J, Tuvia S, Guetta V, et al. Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine. J Am Coll Cardiol, 2009, 54(11): 1014-1023.
18.	Rodell CB, Lee ME, Wang H, et al. Injectable shear-thinning hydrogels for minimally invasive delivery to infarcted myocardium to limit left ventricular remodeling. Circ Cardiovasc Interv, 2016, 9(10): e004058.
19.	Zhu Y, Wood NA, Fok K, et al. Design of a coupled thermoresponsive hydrogel and robotic system for postinfarct biomaterial injection therapy. Ann Thorac Surg, 2016, 102(3): 780-786.
20.	Rao SV, Zeymer U, Douglas PS, et al. A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial infarction: Rationale and design of the PRESERVATION I trial. Am Heart J, 2015, 170(5): 929-937.
21.	Solomon SD, Skali H, Anavekar NS, et al. Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction. Circulation, 2005, 111(25): 3411-3419.
22.	Sack KL, Aliotta E, Choy JS, et al. Intra-myocardial alginate hydrogel injection acts as a left ventricular mid-wall constraint in swine. Acta Biomater, 2020, 111: 170-180.
23.	Leung NHL, Chu DKW, Shiu EYC, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med, 2020, 26(5): 676-680.
24.	Kambe Y, Yamaoka T. Biodegradation of injectable silk fibroin hydrogel prevents negative left ventricular remodeling after myocardial infarction. Biomater Sci, 2019, 7(10): 4153-4165.
25.	Yoshizumi T, Zhu Y, Jiang H, et al. Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction. Biomaterials, 2016, 83: 182-193.
26.	Ruvinov E, Cohen S. Alginate biomaterial for the treatment of myocardial infarction: Progress, translational strategies, and clinical outlook: From ocean algae to patient bedside. Adv Drug Deliv Rev, 2016, 96: 54-76.
27.	Hao T, Li J, Yao F, et al. Injectable fullerenol/alginate hydrogel for suppression of oxidative stress damage in brown adipose-derived stem cells and cardiac repair. ACS Nano, 2017, 11(6): 5474-5488.
28.	Wassenaar JW, Gaetani R, Garcia JJ, et al. Evidence for mechanisms underlying the functional benefits of a myocardial matrix hydrogel for Post-MI treatment. J Am Coll Cardiol, 2016, 67(9): 1074-1086.
29.	Wen Y, Li XY, Li ZY, et al. Intra-myocardial delivery of a novel thermosensitive hydrogel inhibits post-infarct heart failure after degradation in rat. J Cardiovasc Transl Res, 2020, 13(5): 677-685.
30.	Ptaszek LM, Portillo Lara R, Shirzaei Sani E, et al. Gelatin methacryloyl bioadhesive improves survival and reduces scar burden in a mouse model of myocardial infarction. J Am Heart Assoc, 2020, 9(11): e014199.
31.	Zhang C, Hsieh MH, Wu SY, et al. A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function. Biomaterials, 2020, 231: 119672.
32.	Wang X, Pan Z, Cheng Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect, 2020, 105(1): 104-105.
33.	Yang B, Yao F, Hao T, et al. Development of electrically conductive double-network hydrogels via one-step facile strategy for cardiac tissue engineering. Adv Healthc Mater, 2016, 5(4): 474-488.
34.	Mihic A, Cui Z, Wu J, et al. A conductive polymer hydrogel supports cell electrical signaling and improves cardiac function after implantation into myocardial infarct. Circulation, 2015, 132(8): 772-784.
35.	Matsumura Y, Zhu Y, Jiang H, et al. Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction. Biomaterials, 2019, 217: 119289.
36.	Lee RJ, Hinson A, Bauernschmitt R, et al. The feasibility and safety of Algisyl-LVR^TM as a method of left ventricular augmentation in patients with dilated cardiomyopathy: Initial first in man clinical results. Int J Cardiol, 2015, 199: 18-24.
37.	Anker SD, Coats AJ, Cristian G, et al. A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial). Eur Heart J, 2015, 36(34): 2297-2309.
38.	Mann DL, Lee RJ, Coats AJ, et al. One-year follow-up results from AUGMENT-HF: A multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure. Eur J Heart Fail, 2016, 18(3): 314-325.
39.	Frey N, Linke A, Süselbeck T, et al. Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: A first-in-man study. Circ Cardiovasc Interv, 2014, 7(6): 806-812.
40.	Rao SV, Zeymer U, Douglas PS, et al. Bioabsorbable intracoronary matrix for prevention of ventricular remodeling after myocardial infarction. J Am Coll Cardiol, 2016, 68(7): 715-723.
41.	Margulis K, Neofytou EA, Beygui RE, et al. Celecoxib nanoparticles for therapeutic angiogenesis. ACS Nano, 2015, 9(9): 9416-9426.
42.	Liu S, Zhao M, Zhou Y, et al. A self-assembling peptide hydrogel-based drug co-delivery platform to improve tissue repair after ischemia-reperfusion injury. Acta Biomater, 2020, 103: 102-114.
43.	Chen Y, Shi J, Zhang Y, et al. An injectable thermosensitive hydrogel loaded with an ancient natural drug colchicine for myocardial repair after infarction. J Mater Chem B, 2020, 8(5): 980-992.
44.	Yang H, Qin X, Wang H, et al. An in vivo miRNA delivery system for restoring infarcted myocardium. ACS Nano, 2019, 13(9): 9880-9894.
45.	Wang LL, Liu Y, Chung JJ, et al. Local and sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischemic injury. Nat Biomed Eng, 2017, 1: 983-992.
46.	Rufaihah AJ, Johari NA, Vaibavi SR, et al. Dual delivery of VEGF and ANG-1 in ischemic hearts using an injectable hydrogel. Acta Biomater, 2017, 48: 58-67.
47.	Wu Y, Chang T, Chen W, et al. Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction. Bioact Mater, 2020, 6(2): 520-528.
48.	O'Dwyer J, Murphy R, Dolan EB, et al. Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium. Drug Deliv Transl Res, 2020, 10(2): 440-454.
49.	Li H, Gao J, Shang Y, et al. Folic acid derived hydrogel enhances the survival and promotes therapeutic efficacy of iPS cells for acute myocardial infarction. ACS Appl Mater Interfaces, 2018, 10(29): 24459-24468.
50.	Francis MP, Breathwaite E, Bulysheva AA, et al. Human placenta hydrogel reduces scarring in a rat model of cardiac ischemia and enhances cardiomyocyte and stem cell cultures. Acta Biomater, 2017, 52: 92-104.
51.	Ciuffreda MC, Malpasso G, Chokoza C, et al. Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy. Acta Biomater, 2018, 70: 71-83.
52.	Ghanta RK, Aghlara-Fotovat S, Pugazenthi A, et al. Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium. Biomater Sci, 2020, 8(18): 5061-5070.

1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J, 2016, 37(27): 2129-2200.
2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart, 2007, 93(9): 1137-1146.
3. Redfield MM, Jacobsen SJ, Burnett JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: Appreciating the scope of the heart failure epidemic. JAMA, 2003, 289(2): 194-202.
4. Bleumink GS, Knetsch AM, Sturkenboom MC, et al. Quantifying the heart failure epidemic: Prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J, 2004, 25(18): 1614-1619.
5. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol, 2016, 13(6): 368-378.
6. 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2019概要. 中国循环杂志, 2020, 35(9): 833-854.
7. Hao G, Wang X, Chen Z, et al. Prevalence of heart failure and left ventricular dysfunction in China: The China hypertension survey, 2012-2015. Eur J Heart Fail, 2019, 21(11): 1329-1337.
8. Maggioni AP, Dahlström U, Filippatos G, et al. EURObservational Research Programme: Regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail, 2013, 15(7): 808-817.
9. Shah KS, Xu H, Matsouaka RA, et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol, 2017, 70(20): 2476-2486.
10. Gauvin R, Parenteau-Bareil R, Dokmeci MR, et al. Hydrogels and microtechnologies for engineering the cellular microenvironment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2012, 4(3): 235-246.
11. Zhu J, Marchant RE. Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices, 2011, 8(5): 607-626.
12. Batista RA, Otoni CG, Espitia PJP. Chapter 3—Fundamentals of chitosan-based hydrogels: Elaboration and characterization techniques. Holban A, Grumezescu AM, eds. Materials for Biomedical Engineering. The Netherlands: Elsevier, 2019. 61-81.
13. Lee LC, Wall ST, Klepach D, et al. Algisyl-LVR^TM with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart. Int J Cardiol, 2013, 168(3): 2022-2028.
14. Sabbah HN, Wang M, Gupta RC, et al. Augmentation of left ventricular wall thickness with alginate hydrogel implants improves left ventricular function and prevents progressive remodeling in dogs with chronic heart failure. JACC Heart Fail, 2013, 1(3): 252-258.
15. Singelyn JM, DeQuach JA, Seif-Naraghi SB, et al. Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials, 2009, 30(29): 5409-5416.
16. Traverse JH, Henry TD, Dib N, et al. First-in-man study of a cardiac extracellular matrix hydrogel in early and late myocardial infarction patients. JACC Basic Transl Sci, 2019, 4(6): 659-669.
17. Leor J, Tuvia S, Guetta V, et al. Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine. J Am Coll Cardiol, 2009, 54(11): 1014-1023.
18. Rodell CB, Lee ME, Wang H, et al. Injectable shear-thinning hydrogels for minimally invasive delivery to infarcted myocardium to limit left ventricular remodeling. Circ Cardiovasc Interv, 2016, 9(10): e004058.
19. Zhu Y, Wood NA, Fok K, et al. Design of a coupled thermoresponsive hydrogel and robotic system for postinfarct biomaterial injection therapy. Ann Thorac Surg, 2016, 102(3): 780-786.
20. Rao SV, Zeymer U, Douglas PS, et al. A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial infarction: Rationale and design of the PRESERVATION I trial. Am Heart J, 2015, 170(5): 929-937.
21. Solomon SD, Skali H, Anavekar NS, et al. Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction. Circulation, 2005, 111(25): 3411-3419.
22. Sack KL, Aliotta E, Choy JS, et al. Intra-myocardial alginate hydrogel injection acts as a left ventricular mid-wall constraint in swine. Acta Biomater, 2020, 111: 170-180.
23. Leung NHL, Chu DKW, Shiu EYC, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med, 2020, 26(5): 676-680.
24. Kambe Y, Yamaoka T. Biodegradation of injectable silk fibroin hydrogel prevents negative left ventricular remodeling after myocardial infarction. Biomater Sci, 2019, 7(10): 4153-4165.
25. Yoshizumi T, Zhu Y, Jiang H, et al. Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction. Biomaterials, 2016, 83: 182-193.
26. Ruvinov E, Cohen S. Alginate biomaterial for the treatment of myocardial infarction: Progress, translational strategies, and clinical outlook: From ocean algae to patient bedside. Adv Drug Deliv Rev, 2016, 96: 54-76.
27. Hao T, Li J, Yao F, et al. Injectable fullerenol/alginate hydrogel for suppression of oxidative stress damage in brown adipose-derived stem cells and cardiac repair. ACS Nano, 2017, 11(6): 5474-5488.
28. Wassenaar JW, Gaetani R, Garcia JJ, et al. Evidence for mechanisms underlying the functional benefits of a myocardial matrix hydrogel for Post-MI treatment. J Am Coll Cardiol, 2016, 67(9): 1074-1086.
29. Wen Y, Li XY, Li ZY, et al. Intra-myocardial delivery of a novel thermosensitive hydrogel inhibits post-infarct heart failure after degradation in rat. J Cardiovasc Transl Res, 2020, 13(5): 677-685.
30. Ptaszek LM, Portillo Lara R, Shirzaei Sani E, et al. Gelatin methacryloyl bioadhesive improves survival and reduces scar burden in a mouse model of myocardial infarction. J Am Heart Assoc, 2020, 9(11): e014199.
31. Zhang C, Hsieh MH, Wu SY, et al. A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function. Biomaterials, 2020, 231: 119672.
32. Wang X, Pan Z, Cheng Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect, 2020, 105(1): 104-105.
33. Yang B, Yao F, Hao T, et al. Development of electrically conductive double-network hydrogels via one-step facile strategy for cardiac tissue engineering. Adv Healthc Mater, 2016, 5(4): 474-488.
34. Mihic A, Cui Z, Wu J, et al. A conductive polymer hydrogel supports cell electrical signaling and improves cardiac function after implantation into myocardial infarct. Circulation, 2015, 132(8): 772-784.
35. Matsumura Y, Zhu Y, Jiang H, et al. Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction. Biomaterials, 2019, 217: 119289.
36. Lee RJ, Hinson A, Bauernschmitt R, et al. The feasibility and safety of Algisyl-LVR^TM as a method of left ventricular augmentation in patients with dilated cardiomyopathy: Initial first in man clinical results. Int J Cardiol, 2015, 199: 18-24.
37. Anker SD, Coats AJ, Cristian G, et al. A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial). Eur Heart J, 2015, 36(34): 2297-2309.
38. Mann DL, Lee RJ, Coats AJ, et al. One-year follow-up results from AUGMENT-HF: A multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure. Eur J Heart Fail, 2016, 18(3): 314-325.
39. Frey N, Linke A, Süselbeck T, et al. Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: A first-in-man study. Circ Cardiovasc Interv, 2014, 7(6): 806-812.
40. Rao SV, Zeymer U, Douglas PS, et al. Bioabsorbable intracoronary matrix for prevention of ventricular remodeling after myocardial infarction. J Am Coll Cardiol, 2016, 68(7): 715-723.
41. Margulis K, Neofytou EA, Beygui RE, et al. Celecoxib nanoparticles for therapeutic angiogenesis. ACS Nano, 2015, 9(9): 9416-9426.
42. Liu S, Zhao M, Zhou Y, et al. A self-assembling peptide hydrogel-based drug co-delivery platform to improve tissue repair after ischemia-reperfusion injury. Acta Biomater, 2020, 103: 102-114.
43. Chen Y, Shi J, Zhang Y, et al. An injectable thermosensitive hydrogel loaded with an ancient natural drug colchicine for myocardial repair after infarction. J Mater Chem B, 2020, 8(5): 980-992.
44. Yang H, Qin X, Wang H, et al. An in vivo miRNA delivery system for restoring infarcted myocardium. ACS Nano, 2019, 13(9): 9880-9894.
45. Wang LL, Liu Y, Chung JJ, et al. Local and sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischemic injury. Nat Biomed Eng, 2017, 1: 983-992.
46. Rufaihah AJ, Johari NA, Vaibavi SR, et al. Dual delivery of VEGF and ANG-1 in ischemic hearts using an injectable hydrogel. Acta Biomater, 2017, 48: 58-67.
47. Wu Y, Chang T, Chen W, et al. Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction. Bioact Mater, 2020, 6(2): 520-528.
48. O'Dwyer J, Murphy R, Dolan EB, et al. Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium. Drug Deliv Transl Res, 2020, 10(2): 440-454.
49. Li H, Gao J, Shang Y, et al. Folic acid derived hydrogel enhances the survival and promotes therapeutic efficacy of iPS cells for acute myocardial infarction. ACS Appl Mater Interfaces, 2018, 10(29): 24459-24468.
50. Francis MP, Breathwaite E, Bulysheva AA, et al. Human placenta hydrogel reduces scarring in a rat model of cardiac ischemia and enhances cardiomyocyte and stem cell cultures. Acta Biomater, 2017, 52: 92-104.
51. Ciuffreda MC, Malpasso G, Chokoza C, et al. Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy. Acta Biomater, 2018, 70: 71-83.
52. Ghanta RK, Aghlara-Fotovat S, Pugazenthi A, et al. Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium. Biomater Sci, 2020, 8(18): 5061-5070.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Progress in hydrogel implantation in treatment of heart failure

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