Hydrogel applications in myocardial infarction: classification, therapeutic mechanism and clinical translation

Abstract

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide, stemming from the heart’s limited regenerative capacity and formation of noncontractile fibrotic tissue. Current treatments, including pharmacological and surgical interventions, manage symptoms and restore perfusion but fail to promote regeneration. Hydrogel-based therapies offer a promising approach by mimicking the cardiac extracellular matrix (ECM), delivering bioactive molecules, and providing structural support for repair. This systematic review examines recent advances in hydrogel-based cardiac repair, focusing on classification, therapeutic mechanisms, preclinical/clinical findings, and translational challenges. Hydrogels are classified as natural, synthetic, and hybrid ones, each with unique mechanical and biological properties. Key mechanisms include angiogenesis stimulation, inflammation modulation, ECM remodeling, stem cell encapsulation, and electrical conductivity enhancement. Preclinical studies demonstrate reduced infarct size, improved left ventricular function, and enhanced cardiomyocyte survival. However, clinical translation is limited, with few early-stage human trials to date.

Graphical abstract

Keywords

myocardial infarction / hydrogel / cardiac tissue engineering / cardiac repair and regeneration

References

[1] Zou Y, Li L, Li Y, et al. Restoring cardiac functions after myocardial infarction-ischemia/reperfusion via an exosome anchoring conductive hydrogel.ACS Applied Materials & Interfaces, 2021, 13(48): 56892–56908

[2] Gao Y, Hu X, Zhang H, et al. Injectable resveratrol micelles loaded chitosan hydrogel for protecting myocardial cell from injure in oxidative stress microenvironment.International Journal of Biological Macromolecules, 2025, 322(Pt 3): 146803

[3] Cheng N L, Luo Q, Yang Y Q, et al. Injectable pH responsive conductive hydrogel for intelligent delivery of metformin and exosomes to enhance cardiac repair after myocardial ischemia-reperfusion injury.Advanced Science, 2025, 12(24): 2410590

[4] Zheng Z, Guo Z, Zhong F, et al. A dual crosslinked hydrogel-mediated integrated peptides and BMSC therapy for myocardial regeneration.Journal of Controlled Release, 2022, 347: 127–142

[5] Xu J, Brown J, Shaik R, et al. Injectable myocardium-derived hydrogels with SDF-1α releasing for cardiac repair.Biomaterials Advances, 2025, 170: 214203

[6] Liu D, Li Y, Bao Z, et al. Pericardial delivery of sodium alginate-infusible extracellular matrix composite hydrogel promotes angiogenesis and intercellular electrical conduction after myocardial infarction.ACS Applied Materials & Interfaces, 2024, 16(34): 44623–44635

[7] Jia Y B, Wei Z, Feng J T, et al. A heart rate matched patch for mechano-chemical treatment of myocardial infarction: optimal design and transspecies application.Research, 2024, 7: 0517

[8] Rakshit P, Giri T K, Mukherjee K . Progresses and perspectives on natural polysaccharide based hydrogels for repair of infarcted myocardium.International Journal of Biological Macromolecules, 2024, 269(Pt 2): 132213

[9] Zhang J H, Sun D, Guo Y S, et al. Targeted delivery of black phosphorus nanosheets by ROS responsive complex hydrogel based on angiogenesis and antioxidant promotes myocardial infarction repair.Journal of Nanobiotechnology, 2024, 22(1): 433

[10] Yang H, Li J, Shen H, et al. An injectable hydrogel containing versatile nanoparticles with antioxidant and antifibrotic properties for myocardial infarction treatment.Journal of Materials Science and Technology, 2025, 215: 121–130

[11] Sun Y G, Zhao X R, Zhang Q, et al. An immunoregulatory and metabolism-improving injectable hydrogel for cardiac repair after myocardial infarction.Regenerative Biomaterials, 2024, 12: rbae131

[12] Zheng Z, Tan Y, Li Y, et al. Biotherapeutic-loaded injectable hydrogels as a synergistic strategy to support myocardial repair after myocardial infarction.Journal of Controlled Release, 2021, 335: 216–236

[13] Li P, Hu J, Wang J, et al. The role of hydrogel in cardiac repair and regeneration for myocardial infarction: recent advances and future perspectives.Bioengineering, 2023, 10(2): 165

[14] Yang J, Zhou Z, Xie X H, et al. Advances in hydrogel drug delivery systems for myocardial infarction treatment.Journal of Zhejiang University (Medical Sciences), 2025, 54(4): 455–468

[15] Zhang J, Guo Y, Bai Y, et al. Application of biomedical materials in the diagnosis and treatment of myocardial infarction.Journal of Nanobiotechnology, 2023, 21(1): 298

[16] Xu Q, Xiao Z, Yang Q, et al. Hydrogel-based cardiac repair and regeneration function in the treatment of myocardial infarction.Materials Today: Bio, 2024, 25: 100978

[17] Roser S M, Munarin F, Polucha C, et al. Customized heparinized alginate and collagen hydrogels for tunable, local delivery of angiogenic proteins.ACS Biomaterials Science & Engineering, 2025, 11(3): 1612–1628

[18] Luo Q, Li Z, Sun W, et al. Myocardia-injected synergistically anti-apoptotic and anti-inflammatory poly(amino acid) hydrogel relieves ischemia-reperfusion injury.Advanced Materials, 2025, 37(11): 2420171

[19] Wang H, Gui B, Chen Y, et al. Black-phosphorus-reinforced injectable conductive biodegradable hydrogel for the delivery of ADSC-derived exosomes to repair myocardial infarction.ACS Applied Materials & Interfaces, 2024, 16(43): 58286–58298

[20] Liang J H, Lv R H, Li M R, et al. Hydrogels for the treatment of myocardial infarction: design and therapeutic strategies.Macromolecular Bioscience, 2024, 24(2): 2300302

[21] Wang D, Zhang H, Chen Y, et al. Improving therapeutic effects of exosomes encapsulated gelatin methacryloyl/hyaluronic acid blended and oxygen releasing injectable hydrogel by cardiomyocytes induction and vascularization in rat myocardial infarction model.International Journal of Biological Macromolecules, 2024, 271(Pt 2): 132412

[22] Zhao J L, Chen Y, Qin Y Y, et al. Adhesive and conductive hydrogels for the treatment of myocardial infarction.Macromolecular Rapid Communications, 2025, 46(5): 2400835

[23] Xu H, Zhao Z Y, She P Y, et al. Salvaging myocardial infarction with nanoenzyme-loaded hydrogels: targeted scavenging of mitochondrial reactive oxygen species.Journal of Controlled Release, 2024, 375: 788–801

[24] Ren Y C, Wang W T, Yu C J, et al. An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.International Journal of Biological Macromolecules, 2024, 275(Pt 2): 133622

[25] Wang M, Dai T M, Zhu D . Design and development of nanoselenium‒ruthenium/collagen-loaded multifunctional injectable hydrogel delivery for promising treatment of myocardial infarction.Journal of Drug Delivery Science and Technology, 2025, 104: 106522

[26] Gao H, Liu S, Qin S S, et al. Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and meta-analysis of preclinical trials.BMC Cardiovascular Disorders, 2024, 24(1): 119

[27] Alamdari S G, Alibakhshi A, de la Guardia M, et al. Conductive and semiconductive nanocomposite-based hydrogels for cardiac tissue engineering.Advanced Healthcare Materials, 2022, 11(18): 2200526

[28] Nicoletti L. New advanced therapies for drug delivery in cardiac regeneration. Dissertation for the Doctoral Degree. Turin: Polytechnic University of Turin, 2024, 267 (in Italian)

[29] Zhang W, Peng D, Cheng S, et al. Inflammatory cell-targeted delivery systems for myocardial infarction treatment.Bioengineering, 2025, 12(2): 205

[30] Xiang K, Zheng Z L, Li Y C, et al. Application of PLGA‒PEG‒PLGA thermosensitive hydrogel loaded with human induced pluripotent stem cell-derived cardiomyocytes and ginsenoside Rb3 in the treatment of acute myocardial infarction.Circulation, 2024, 150(Suppl_1): A4137339

[31] Yang M, Wang L, Liu W, et al. Highly-stable, injectable, conductive hydrogel for chronic neuromodulation.Nature Communications, 2024, 15(1): 7993

[32] Radhakrishnan J, Krishnan U M, Sethuraman S . Hydrogel based injectable scaffolds for cardiac tissue regeneration.Biotechnology Advances, 2014, 32(2): 449–461

[33] Sakr M A, Sakthivel K, Hossain T, et al. Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering.Journal of Biomedical Materials Research Part A, 2022, 110(3): 708–724

[34] Sepantafar M, Maheronnaghsh R, Mohammadi H, et al. Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair.Biotechnology Advances, 2016, 34(4): 362–379

[35] Song X, Wang X, Zhang J, et al. A tunable self-healing ionic hydrogel with microscopic homogeneous conductivity as a cardiac patch for myocardial infarction repair.Biomaterials, 2021, 273: 120811

[36] Suhar R A, Doulames V M, Liu Y, et al. Hyaluronan and elastin-like protein (HELP) gels significantly improve microsphere retention in the myocardium.Biomaterials Science, 2022, 10(10): 2590–2608

[37] Atluri P, Miller J S, Emery R J, et al. Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function.Journal of Thoracic and Cardiovascular Surgery, 2014, 148(3): 1097–1098

[38] Sun X, Nunes S S . Overview of hydrogel-based strategies for application in cardiac tissue regeneration.Biomedical Materials, 2015, 10(3): 034005

[39] Jia J Q, Lei Q, Zhang X M, et al. Melt-electrowriting fibrous scaffolds modified with nano-topography structures promoting cardiomyocytes synergistic contraction.Materials Today: Bio, 2026, 36: 102654

[40] Lei Q, Jia J, Guan X, et al. Electrohydrodynamic printing of microscale fibrous scaffolds with a sinusoidal structure for enhancing the contractility of cardiomyocytes.ACS Biomaterials Science & Engineering, 2024, 10(11): 7227–7234

[41] Amini H, Namjoo A R, Narmi M T, et al. Exosome-bearing hydrogels and cardiac tissue regeneration.Biomaterials Research, 2023, 27(1): 99

[42] Cao Y, Fan R, Zhu K, et al. Advances in functionalized hydrogels in the treatment of myocardial infarction and drug-delivery strategies.ACS Applied Materials & Interfaces, 2024, 16(37): 48880–48894

[43] Barabadi Z, Azami M, Sharifi E, et al. Fabrication of hydrogel based nanocomposite scaffold containing bioactive glass nanoparticles for myocardial tissue engineering.Materials Science and Engineering C, 2016, 69: 1137–1146

[44] Cattelan G, Guerrero Gerbolés A, Foresti R, et al. Alginate formulations: current developments in the race for hydrogel-based cardiac regeneration.Frontiers in Bioengineering and Biotechnology, 2020, 8: 414

[45] Chen Y, Li C, Li C, et al. Tailorable hydrogel improves retention and cardioprotection of intramyocardial transplanted mesenchymal stem cells for the treatment of acute myocardial infarction in mice.Journal of the American Heart Association, 2020, 9(2): e013784

[46] Maeso L, Eufrásio-da-Silva T, Deveci E, et al. Latest progress of self-healing hydrogels in cardiac tissue engineering.Biomedical Microdevices, 2024, 26(3): 36

[47] Chen X, Zhu L, Wang X, et al. Insight into heart-tailored architectures of hydrogel to restore cardiac functions after myocardial infarction.Molecular Pharmaceutics, 2023, 20(1): 57–81

[48] Chen W X, Ming Y, Wang M, et al. Nanocomposite hydrogels in regenerative medicine: applications and challenges.Macromolecular Rapid Communications, 2023, 44(15): 2300128

[49] Deng K C, Hua Y Y, Gao Y, et al. Thermosensitive hydrogel with programmable, self-regulated HIF-1α stabilizer release for myocardial infarction treatment.Advanced Science, 2024, 11(43): 2408013

[50] Contessotto P, Pandit A . Therapies to prevent post-infarction remodelling: from repair to regeneration.Biomaterials, 2021, 275: 120906

[51] Contessotto P, Orbanić D, Da Costa M, et al. Elastin-like recombinamers-based hydrogel modulates post-ischemic remodeling in a non-transmural myocardial infarction in sheep.Science Translational Medicine, 2021, 13(581): eaaz5380

[52] Rocker A J, Cavasin M, Johnson N R, et al. Sulfonated thermoresponsive injectable gel for sequential release of therapeutic proteins to protect cardiac function after myocardial infarction.ACS Biomaterials Science & Engineering, 2022, 8(9): 3883–3898

[53] Yuan Z, Tsou Y H, Zhang X Q, et al. Injectable citrate-based hydrogel as an angiogenic biomaterial improves cardiac repair after myocardial infarction.ACS Applied Materials & Interfaces, 2019, 11(42): 38429–38439

[54] Yang P, Shi Y, Hu H, et al. Inhibition of neuron and cardiac remodeling by microenvironment-responsive injectable hydrogels with sympatho-immune regulation properties for myocardial infarction therapy.Composites Part B: Engineering, 2025, 297: 112300

[55] Yi B C, Xu Y W, Wang X Y, et al. Overview of injectable hydrogels for the treatment of myocardial infarction.Cardiovascular Innovations and Applications, 2024, 9(1): 960

[56] Tariq U, Gupta M, Pathak S, et al. Role of biomaterials in cardiac repair and regeneration: therapeutic intervention for myocardial infarction.ACS Biomaterials Science & Engineering, 2022, 8(8): 3271–3298

[57] Xiong Z, An Q, Chen L, et al. Cell or cell derivative-laden hydrogels for myocardial infarction therapy: from the perspective of cell types.Journal of Materials Chemistry B, 2023, 11(41): 9867–9888

[58] Wu T L, Liu W G . Functional hydrogels for the treatment of myocardial infarction.NPG Asia Materials, 2022, 14: 9

[59] Xia Y, Zhu K, Lai H, et al. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation.Experimental Biology and Medicine, 2015, 240(5): 593–600

[60] Wang S Q, Yao Y J, Zhou T, et al. Preservation of cardiac functions post myocardial infarction in vivo by a phenylboric acid-grafted hyaluronic hydrogel with anti-oxidation and accelerated degradation under oxidative microenvironment.Composites Part B: Engineering, 2022, 238: 109941

[61] Luo Q, Li Z, Liu B, et al. Hydrogel formulations for orthotopic treatment of myocardial infarction.Expert Opinion on Drug Delivery, 2024, 21(10): 1463–1478

[62] Wassenaar J W, Gaetani R, Garcia J J, et al. Evidence for mechanisms underlying the functional benefits of a myocardial matrix hydrogel for post-MI treatment.Journal of the American College of Cardiology, 2016, 67(9): 1074–1086

[63] Huang S H, Hong X Q, Zhao M Y, et al. Nanocomposite hydrogels for biomedical applications.Bioengineering & Translational Medicine, 2022, 7(3): e10315

[64] Jang J, Park H J, Kim S W, et al. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.Biomaterials, 2017, 112: 264–274

[65] Dai Y, Qiao K, Li D, et al. Plant-derived biomaterials and their potential in cardiac tissue repair.Advanced Healthcare Materials, 2023, 12(20): 2202827

[66] Vasu S, Zhou J, Chen J, et al. Biomaterials-based approaches for cardiac regeneration.Korean Circulation Journal, 2021, 51(12): 943–960

[67] Tan H L, Teow S Y, Pushpamalar J . Application of metal nanoparticle‒hydrogel composites in tissue regeneration.Bioengineering, 2019, 6(1): 17

[68] Pournemati B, Tabesh H, Jenabi A, et al. Injectable conductive nanocomposite hydrogels for cardiac tissue engineering: focusing on carbon and metal-based nanostructures.European Polymer Journal, 2022, 174: 111336

[69] Hu W, Yang C, Guo X, et al. Research advances of injectable functional hydrogel materials in the treatment of myocardial infarction.Gels, 2022, 8(7): 423

[70] Paul A . Nanocomposite hydrogels: an emerging biomimetic platform for myocardial therapy and tissue engineering.Nanomedicine, 2015, 10(9): 1371–1374

[71] Patil R, Rajput A, Dewani M, , et al. Hydrogel-based therapies for cardiovascular diseases. Engineering Materials for Stem Cell Regeneration, 2021, 399–427

[72] Rotaru-Zăvăleanu A D, Dinescu V C, Aldea M, et al. Hydrogel-based therapies for ischemic and hemorrhagic stroke: a comprehensive review.Gels, 2024, 10(7): 476

[73] Rocca D G D, Willenberg B J, Qi Y, et al. An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.International Journal of Cardiology, 2016, 220: 149–154

[74] Jiang Y L, Niu S, Lin Z, et al. Injectable hydrogel with dual-sensitive behavior for targeted delivery of oncostatin M to improve cardiac restoration after myocardial infarction.Journal of Materials Chemistry B, 2022, 10(34): 6514–6531

[75] Holme S, Richardson S M, Bella J, et al. Hydrogels for cardiac tissue regeneration: current and future developments.International Journal of Molecular Sciences, 2025, 26(5): 2309

[76] Mikłosz A, Chabowski A . Efficacy of adipose-derived mesenchymal stem cell therapy in the treatment of chronic micro- and macrovascular complications of diabetes.Diabetes, Obesity and Metabolism, 2024, 26(3): 793–808

[77] Duong T K N, Truong T T, Phan T N L, et al. Hydrogel-based smart materials for wound healing and sensing.Aggregate, 2025, 6(6): e70047

[78] Motta I, Soccio M, Guidotti G, et al. Hydrogels for cardio and vascular tissue repair and regeneration.Gels, 2024, 10(3): 196

[79] Richbourg N, Wechsler M E, Rodriguez-Cruz J J, et al. Model-based modular hydrogel design.Nature Reviews: Bioengineering, 2024, 2(7): 575–587

[80] Dorsey S M, McGarvey J R, Wang H, et al. MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.Biomaterials, 2015, 69: 65–75

[81] 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

[82] He S Y, Zhang Z Y, Luo R F, et al. Advances in injectable hydrogel strategies for heart failure treatment.Advanced Healthcare Materials, 2023, 12(19): e2300029

[83] Lee M, Kim M C, Lee J Y . Nanomaterial-based electrically conductive hydrogels for cardiac tissue repair.International Journal of Nanomedicine, 2022, 17: 6181–6200

[84] Efraim Y, Sarig H, Cohen Anavy N, et al. Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.Acta Biomaterialia, 2017, 50: 220–233

[85] Kim K M, D’Elia A M, Rodell C B . Hydrogel-based approaches to target hypersensitivity mechanisms underlying autoimmune disease.Advanced Drug Delivery Reviews, 2024, 212: 115395

[86] Lu Y, Luo Y, Zhu R, et al. Advanced bioactive hydrogels for the treatment of myocardial infarction.Journal of Materials Chemistry B, 2022, 10(41): 8375–8385

[87] Fang J, Koh J, Fang Q, et al. Injectable drug-releasing microporous annealed particle scaffolds for treating myocardial infarction.Advanced Functional Materials, 2020, 30(43): 2004307

[88] Feng J, Xing M, Qian W, et al. An injectable hydrogel combining medicine and matrix with anti-inflammatory and pro-angiogenic properties for potential treatment of myocardial infarction.Regenerative Biomaterials, 2023, 10: rbad036

[89] Hassanpour P, Sadeghsoltani F, Haiaty S, et al. Mitochondria-loaded alginate-based hydrogel accelerated angiogenesis in a rat model of acute myocardial infarction.International Journal of Biological Macromolecules, 2024, 260(Pt 2): 129633

[90] 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 Applied Materials & Interfaces, 2018, 10(29): 24459–24468

[91] Jeong J O, Kim M, Kim S, et al. Advanced hydrogel systems for local anesthetic delivery: toward prolonged and targeted pain relief.Gels, 2025, 11(2): 131

[92] Tsintou M, Dalamagkas K, Moore T L, et al. The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke: a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches.Neural Regeneration Research, 2021, 16(4): 605–613

[93] Lin S Y, Zhu Y Y, Hu T T, et al. Novel design of nano-selenium loaded injectable hydrogel combined with mesenchymal stem cells-derived exosomes improving cardiac repair and nursing care after acute myocardial infarction.Journal of Drug Delivery Science and Technology, 2023, 87: 104711

[94] Kowala A, Boot J, Meng J H, et al. Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment.Cell Reports Medicine, 2025, 6(3): 102019

[95] Liao X, Yang X, Deng H, et al. Injectable hydrogel-based nanocomposites for cardiovascular diseases.Frontiers in Bioengineering and Biotechnology, 2020, 8: 251

[96] Alfaqeh H H, Idrus R B H, Saim A B, et al. Synergistic effects of natural products and mesenchymal stem cells in osteoarthritis treatment: a narrative review.Current Issues in Molecular Biology, 2025, 47(6): 445

[97] Hasan A, Khattab A, Islam M A, et al. Injectable hydrogels for cardiac tissue repair after myocardial infarction.Advanced Science, 2015, 2(11): 1500122

[98] Li X, Lu P, Liu Z, et al. An anisotropic electromagnetic hydrogel promotes cardiomyocyte maturation and post-infarction cardiac repair.Chemical Engineering Journal, 2023, 476: 146745

[99] Giraud M N, Ayuni E, Cook S, et al. Hydrogel-based engineered skeletal muscle grafts normalize heart function early after myocardial infarction.Artificial Organs, 2008, 32(9): 692–700

[100] Omidian H, Akhzarmehr A, Chowdhury S D . Hydrogel composites for multifunctional biomedical applications.Journal of Composites Science, 2024, 8(4): 154

[101] Guan H, Chen Y, Liu X, et al. Research and application of hydrogel-encapsulated mesenchymal stem cells in the treatment of myocardial infarction.Colloids and Surfaces B: Biointerfaces, 2024, 239: 113942

[102] Truong D, Wu K Y, Nguyen L, et al. Advancements in hydrogel technology for ocular drug delivery.Exploration of BioMat-X, 2024, 1(5): 331–352

[103] Tang W, Chen S, Zhang S, et al. The multi-dimensional role of vitamin d in the pathophysiology and treatment of diabetic foot ulcers: from molecular mechanisms to clinical translation.International Journal of Molecular Sciences, 2025, 26(12): 5719

[104] Guan S, Li J, Zhang K, et al. Environmentally responsive hydrogels for repair of cardiovascular tissue.Heart Failure Reviews, 2021, 26(5): 1273–1285

[105] Correa S, Grosskopf A K, Lopez Hernandez H, et al. Translational applications of hydrogels.Chemical Reviews, 2021, 121(18): 11385–11457

[106] Li Z T, Li Q, Cao W D, et al. A strongly robust chitosan-based programmed control functional hydrogel improved mitochondrial function and pro-vascularization for adaptive repair of myocardial infarction.Advanced Functional Materials, 2024, 34(16): 2312631

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