Shi, H. P. et al. Microneedle-mediated gene delivery for the treatment of ischemic myocardial disease. Sci. Adv. 6, eaaz3621 (2020).
Google Scholar
Wu, Y. et al. Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of MI. Bioact. Mater. 6, 520–528 (2021).
Google Scholar
Lin, X. et al. A viscoelastic adhesive epicardial patch for treating MI. Nat. Biomed. Eng. 3, 632–643 (2019).
Google Scholar
Fiedler, J. & Thum, T. MicroRNAs in MI. Arterioscler Thromb. Vasc. Biol. 33, 201–205 (2013).
Google Scholar
Sepantafar, M. et al. Stem cells and injectable hydrogels: synergistic therapeutics in myocardial repair. Biotechnol. Adv. 34, 362–379 (2016).
Google Scholar
Pena, B. et al. Injectable hydrogels for cardiac tissue engineering. Macromol. Biosci. 18, 1800079 (2018).
Heallen, T. R. & Martin, J. F. Heart repair via cardiomyocyte-secreted vesicles. Nat. Biomed. Eng. 2, 271–272 (2018).
Hashimoto, H., Olson, E. N. & Bassel-Duby, R. Therapeutic approaches for cardiac regeneration and repair. Nat. Rev. Cardiol. 15, 585–600 (2018).
Marban, E. A mechanistic roadmap for the clinical application of cardiac cell therapies. Nat. Biomed. Eng. 2, 353–361 (2018).
Zhang, Y. et al. A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent mode. Acta Biomater. 86, 223–234 (2019).
Li, H. K. et al. Folic acid-derived hydrogel enhances the survival and promotes therapeutic efficacy of iPS cells for acute MI. ACS Appl. Mater. Interfaces 10, 24459–24468 (2018).
Google Scholar
Wu, T. L. et al. Coadministration of an adhesive conductive hydrogel patch and an injectable hydrogel to treat MI. ACS Appl. Mater. Interfaces 12, 2039–2048 (2020).
Google Scholar
Jackman, C. P. et al. Engineered cardiac tissue patch maintains structural and electrical properties after epicardial implantation. Biomaterials 159, 48–58 (2018).
Google Scholar
Pedron, S. et al. Stimuli responsive delivery vehicles for cardiac microtissue transplantation. Adv. Funct. Mater. 21, 1624–1630 (2011).
Google Scholar
Peña, B. et al. Injectable hydrogels for cardiac tissue engineering. Macromol. Biosci. 18, 1800079 (2018).
Camci-Unal, G., Annabi, N., Dokmeci, M. R., Liao, R. & Khademhosseini, A. Hydrogels for cardiac tissue engineering. NPG Asia. Mater. 6, e99 (2014).
Google Scholar
Nguyen, M. M. et al. Enzyme-responsive nanoparticles for targeted accumulation and prolonged retention in heart tissue after MI. Adv. Mater. 27, 5547–5552 (2015).
Google Scholar
Kampourides, N. et al. Usefulness of matrix metalloproteinase-9 plasma levels to identify patients with preserved left ventricular systolic function after acute MI who could benefit from eplerenone. Am. J. Cardiol. 110, 1085–1091 (2012).
Google Scholar
Zhang, Y. et al. Biomimetic design of mitochondria-targeted hybrid nanozymes as superoxide scavengers. Adv. Mater. 33, 2006570 (2021).
Google Scholar
Yao, Y. J. et al. ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo. Biomaterials 232, 119726 (2020).
Google Scholar
McMahan, S. et al. Current advances in biodegradable synthetic polymer based cardiac patches. J. Biomed. Mater. Res. 108, 972–983 (2020).
Google Scholar
Li, Y. et al. Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for MI therapy in pigs. Sci. Adv. 7, eabd6740 (2021).
Google Scholar
Purcell, B. P. et al. Delivery of a matrix metalloproteinase-responsive hydrogel releasing TIMP-3 after MI: effects on left ventricular remodeling. Am. J. Physiol. Heart Circ. Physiol. 315, H814–H825 (2018).
Google Scholar
Creemers, E. E. J. M., Cleutjens, J. P. M., Smits, J. F. M. & Daemen, M. J. A. P. Matrix metalloproteinase inhibition after MI-A new approach to prevent heart failure? Circ. Res. 89, 201–210 (2001).
Google Scholar
Wang, K. F. et al. Usefulness of plasma matrix metalloproteinase-9 level in predicting future coronary revascularization in patients after acute MI. Coron. Artery Dis. 24, 23–28 (2013).
Sun, Y. Myocardial repair/remodelling following infarction: roles of local factors. Cardiovasc. Res. 81, 482–490 (2009).
Google Scholar
Spaulding, K. A. et al. Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility. J. Biomed. Mater. Res. A 108, 1736–1746 (2020).
Google Scholar
Bloise, N. et al. Engineering immunomodulatory biomaterials for regenerating the infarcted myocardium. Front. Bioeng. Biotech. 8, 292 (2020).
Zhao, G. X. et al. Anisotropic conductive reduced graphene oxide/silk matrices promote post-infarction myocardial function by restoring electrical integrity. Acta Biomater. https://doi.org/10.1016/j.actbio.2021.03.073 (2021).
Song, C. et al. An injectable conductive three-dimensional elastic network by tangled surgical-suture spring for heart repair. ACS Nano 13, 14122–14137 (2019).
Google Scholar
Wang, L. L. et al. Sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischaemic injury. Nat. Biomed. Eng. 1, 983–992 (2017).
Google Scholar
Wall, S. T., Walker, J. C., Healy, K. E., Ratcliffe, M. B. & Guccione, J. M. Theoretical impact of the injection of material into the myocardium. Circulation 114, 2627–2635 (2006).
Zhu, Y., Matsumura, Y. & Wagner, W. R. Ventricular wall biomaterial injection therapy after MI: advances in material design, mechanistic insight and early clinical experiences. Biomaterials 129, 37–53 (2017).
Google Scholar
Park, S. J. et al. Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following MI. Nat. Commun. 10, 3123 (2019).
Huang, K. et al. An off-the-shelf artificial cardiac patch improves cardiac repair after MI in rats and pigs. Sci. Transl. Med. 12, eaat9683 (2020).
Gustafson, J. A. et al. Synthesis and characterization of a matrix-metalloproteinase responsive silk-elastinlike protein polymer. Biomacromolecules 14, 618–625 (2013).
Google Scholar
Fonseca, K. B. et al. Enzymatic, physicochemical and biological properties of MMP-sensitive alginate hydrogels. Soft Matter 9, 3283–3292 (2013).
Google Scholar
Martin, J. R., Patil, P., Yu, F., Gupta, M. K. & Duvall, C. L. Enhanced stem cell retention and antioxidative protection with injectable, ROS-degradable PEG hydrogels. Biomaterials 263, 120377 (2021).
Cheng, H. et al. Sprayable hydrogel dressing accelerates wound healing with combined reactive oxygen species-scavenging and antibacterial abilities. Acta Biomater. 124, 219–232 (2021).
Google Scholar
Zhou, J. et al. Injectable OPF/graphene oxide hydrogels provide mechanical support and enhance cell electrical signaling after implantation into myocardial infarct. Theranostics 8, 3317–3330 (2018).
Google Scholar
Kim, D. H. et al. Guided three-dimensional growth of functional cardiomyocytes on polyethylene glycol nanostructures. Langmuir 22, 5419–5426 (2006).
Google Scholar
Madden, L. R. et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc. Natl Acad. Sci. USA 107, 15211–15216 (2010).
Google Scholar
Soler-Botija, C., Galvez-Monton, C., Prat-Vidal, C., Roura, S. & Bayes-Genis, A. Myocardial bioprosthesis: mimicking nature. Drug. Future 38, 475–484 (2013).
Liu, J. et al. Direct 3D bioprinting of cardiac micro-tissues mimicking native myocardium. Biomaterials 256, 120204 (2020).
Google Scholar
Lee, A. et al. 3D bioprinting of collagen to rebuild components of the human heart. Science 365, 482–487 (2019).
Google Scholar
Maral, S. et al. Matrix metalloproteinases 2 and 9 polymorphism in patients with myeloproliferative diseases. Medicine 94, e732 (2015).
Google Scholar
West, J. B., Watson, R. R. & Fu, Z. X. The honeycomb-like structure of the bird lung allows a uniquely thin blood-gas barrier. Resp. Physiol. Neurobi. 152, 115–118 (2006).
Noujaim, D., van Golen, C. M., van Golen, K. L., Grauman, A. & Feldman, E. L. N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells. Oncogene 21, 4549–4557 (2002).
Google Scholar
Wada, C. K. et al. Phenoxyphenyl sulfone N-formylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors. J. Med. Chem. 45, 219–232 (2002).
Google Scholar
Michaelides, M. R. & Curtin, M. L. Recent advances in matrix metalloproteinase inhibitor research. Curr. Pharm. Des. 5, 787–819 (1999).
Google Scholar
Eckhouse, S. R. et al. Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular remodeling after experimental MI. Sci. Transl. Med. 6, 223ra21 (2014).
Zavadzkas, J. A. et al. Targeted overexpression of tissue inhibitor of matrix metalloproteinase-4 modifies post-MI remodeling in mice. Circ. Res. 114, 1435–1445 (2014).
Google Scholar
Carlini, A. S. et al. Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction. Nat. Commun. 10, 1735 (2019).
Fan, Z. B. et al. Sustained release of a peptide-based matrix metalloproteinase‑2 inhibitor to attenuate adverse cardiac remodeling and improve cardiac function following MI. Biomacromolecules 18, 2820–2829 (2017).
Google Scholar
Purcell, B. P. et al. Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat. Mater. 13, 653–661 (2014).
Google Scholar
Fan, C. X. et al. Myocardial-infarction-responsive smart hydrogels targeting matrix metalloproteinase for on-demand growth factor delivery. Adv. Mater. 31, 1902900 (2019).
Google Scholar
Xu, Q., He, C., Xiao, C. & Chen, X. Reactive oxygen species (Ros) responsive polymers for biomedical applications. Macromol. Biosci. 16, 635–646 (2016).
Google Scholar
Huo, M., Yuan, J., Tao, L. & Wei, Y. Redox-responsive polymers for drug delivery: from molecular design to applications. Polym. Chem. 5, 1519–1528 (2014).
Google Scholar
Wang, W. et al. Rebuilding postinfarcted cardiac functions by injecting TIIA@ PDA nanoparticle-cross-linked ROS-sensitive hydrogels. ACS Appl. Mater. Interfaces 11, 2880–2890 (2018).
Han, X. X. et al. “Ferrero-like” nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts. Sci. China Tech. Sci. 63, 2435–2448 (2020).
Google Scholar
Ding, J. et al. A reactive oxygen species scavenging and O2 generating injectable hydrogel for MI treatment in vivo. Small 16, 2005038 (2020).
Google Scholar
Zhu, Y. et al. Reactive oxygen species scavenging with a biodegradable, thermally responsive hydrogel compatible with soft tissue injection. Biomaterials 177, 98e112 (2018).
Li, J. J. et al. A chitosaneglutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes. Biomaterials 34, 9071e9081 (2013).
Liu, Z. Q. et al. The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials 33, 3093e3106 (2012).
Hao, T. et al. Injectable fullerenol/alginate hydrogel for suppression of oxidative stress damage in brown adipose-derived stem cells and cardiac repair. ACS Nano 11, 5474–5488 (2017).
Google Scholar
Swirski, F. K. & Nahrendorf, M. Cardioimmunology: the immune system in cardiac homeostasis and disease. Nat. Rev. Immunol. 18, 733–744 (2018).
Google Scholar
Frangogiannis, N. G. et al. Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98, 699–710 (1998).
Google Scholar
Anzai, A. et al. The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes. J. Exp. Med. 214, 3293–3310 (2017).
Google Scholar
Nikolaos, G. F. The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities. J. Cardiovasc. Pharmacol. 63, 83–84 (2014).
Kobara, M. et al. Antibody against interleukin-6 receptor attenuates left ventricular remodelling after myocardial infarction in mice. Cardiovasc. Res. 87, 424–430 (2010).
Google Scholar
Marta, M. T. et al. Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction. Bioact. Mater. 6, 3314–3327 (2021).
Liu, Y. et al. Chitosan hydrogel enhances the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction by alleviating vascular endothelial cell pyroptosis. J. Cardiovasc. Pharmacol. 75, 75–83 (2020).
Google Scholar
Shin, E. Y. et al. Adenosine production by biomaterial-supported mesenchymal stromal cells reduces the innate inflammatory response in myocardial ischemia/reperfusion injury. J. Am. Heart Assoc. 7, e006949 (2018).
Duan, Y. Y. et al. Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis. Biomaterials 246, 120012 (2020).
Google Scholar
Liu, G. et al. Enhancement of cardiac function with spleen-specific hydrogel via improving the immune microenvironment after myocardial infarction. J. Biomater. Tiss. Eng. 7, 458–468 (2017).
Lv, K. Q. et al. Incorporation of small extracellular vesicles in sodium alginate hydrogel as a novel therapeutic strategy for myocardial infarction. Theranostics 9, 7403–7416 (2019).
Google Scholar
Li, Y. et al. Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs. Sci. Adv. 7, eabd6740 (2021).
Google Scholar
Zhang, X. P. et al. Artificial apoptotic cells/VEGF-loaded injectable hydrogel united with immunomodification and revascularization functions to reduce cardiac remodeling after myocardial infarction. Nano Today 39, 101227 (2021).
Google Scholar
Hofmann, U. et al. Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125, 1652–U146 (2012).
Google Scholar
Weirather, J. et al. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ. Res. 115, 55–67 (2014).
Google Scholar
Zacchigna, S. et al. Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction. Nat. Commun. 9, 2432 (2018).
Bao, R. et al. A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after MI. Biomaterials 122, 63–71 (2017).
Google Scholar
Wang, L. L. et al. Mussel-inspired conductive cryogel as cardiac tissue patch to repair MI by migration of conductive nanoparticles. Adv. Funct. Mater. 26, 4293–4305 (2016).
Google Scholar
Hsiao, C. W. et al. Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating. Biomaterials 34, 1063–1072 (2013).
Google Scholar
Song, X. P. et al. A tunable self-healing ionic hydrogel with microscopic homogeneous conductivity as a cardiac patch for MI repair. Biomaterials 273, 120811 (2021).
Google Scholar
Qazi, T. H., Rai, R. & Boccaccini, A. R. Tissue engineering of electrically responsive tissues using polyaniline based polymers: a review. Biomaterials 35, 9068–9086 (2014).
Google Scholar
Kai, D., Prabhakaran, M. P., Jin, G. & Ramakrishna, S. Polypyrrole-contained electrospun conductive nanofibrous membranes for cardiac tissue engineering. J. Biomed. Mater. Res. A 99, 376–385 (2011).
Navaei, A. et al. Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs. Acta Biomater. 41, 133–146 (2016).
Google Scholar
Pok, S. et al. Biocompatible carbon nanotube-chitosan scaffold matching the electrical conductivity of the heart. ACS Nano 8, 9822–9832 (2014).
Google Scholar
Mihic, A. et al. A conductive polymer hydrogel supports cell electrical signaling and improves cardiac function after implantation into myocardial infarct. Circulation 132, 772–784 (2015).
Google Scholar
Wang, W. et al. An injectable conductive hydrogel encapsulating plasmid DNA-eNOs and ADSCs for treating MI. Biomaterials 160, 69–81 (2018).
Google Scholar
Liang, S. et al. Paintable and rapidly bondable conductive hydrogels as therapeutic cardiac patches. Adv. Mater. 30, 1704235 (2018).
He, S. et al. The conductive function of biopolymer corrects myocardial scar conduction blockage and resynchronizes contraction to prevent heart failure. Biomaterials 258, 120285 (2020).
Google Scholar
Motealleh, A. & Kehr, N. S. Nanocomposite hydrogels and their applications in tissue engineering. Adv. Healthc. Mater. 6, 1600938 (2017).
Lei, Z. Y. & Wu, P. Y. A highly transparent and ultra-stretchable conductor with stable conductivity during large deformation. Nat. Commun. 10, 3429 (2019).
Noshadi, I. et al. Engineering biodegradable and biocompatible bio-ionic liquid conjugated hydrogels with tunable conductivity and mechanical properties. Sci. Rep. 7, 4345 (2017).
Liu, Y. et al. One zwitterionic injectable hydrogel with ion conductivity enables efficient restoration of cardiac function after MI. Chem. Eng. J. 418, 129352 (2021).
Google Scholar
Zhao, Q. & Li, Z. J. Angiogenesis. BioMed. Res. Int. 2015, 135861 (2015).
Awada, H. K., Johnson, N. R. & Wang, Y. D. Sequential delivery of angiogenic growth factors improves revascularization and heart function after MI. J. Control. Release 207, 7–17 (2015).
Google Scholar
Yuan, Z. Z. et al. Injectable citrate-based hydrogel as an angiogenic biomaterial improves cardiac repair after MI. ACS Appl. Mater. Interfaces 11, 38429–38439 (2019).
Google Scholar
Massion, P. B., Feron, O., Dessy, C. & Balligand, J. L. Nitric oxide and cardiac function ten years after, and continuing. Circ. Res. 93, 388–398 (2003).
Google Scholar
Lundberg, J. O., Weitzberg, E. & Gladwin, M. T. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 7, 156–167 (2008).
Google Scholar
Qin, Q. et al. Exogenous NO triggers preconditioning via a cGMP-and mitoKATP-dependent mechanism. Am. J. Physiol.-Heart C. 287, H712–H718 (2004).
Google Scholar
Yao, X. P. et al. Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for MI. Biomaterials 60, 130e140 (2015).
Chen, G. Q. et al. A Mixed Component supramolecular hydrogel to improve mice cardiac function and alleviate ventricular remodeling after acute MI. Adv. Funct. Mater. 27, 1701798 (2017).
Vong, L. B. et al. Novel angiogenesis therapeutics by redox injectable hydrogel-Regulation of local nitric oxide generation for effective cardiovascular therapy. Biomaterials 167, 143e152 (2018).
Rufaihah, A. J. et al. Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model. Biomaterials 34, 8195–8202 (2013).
Google Scholar
Munarin, F., Kant, R. J., Rupert, C. E., Khoo, A. & Coulombe, K. L. K. Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts. Biomaterials 251, 120033 (2020).
Google Scholar
Lee, S. et al. Human-recombinant-elastin-based bioinks for 3D bioprinting of vascularized soft tissues. Adv. Mater. 32, 2003915 (2020).
Google Scholar
Noor, N. et al. 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv. Sci. 6, 1900344 (2019).
Motterlini, R. & Otterbein, L. E. The therapeutic potential of carbon monoxide. Nat. Rev. Drug Discov. 9, 728–U24 (2010).
Google Scholar
Wang, W. L., Ge, T. Y., Chen, X., Mao, Y. C. & Zhu, Y. Z. Advances in the protective mechanism of NO, H2S, and H2 in myocardial ischemic injury. Front. Cardiovasc. Med. 7, 588206 (2020).
Google Scholar
Kim, I. et al. Supramolecular carbon monoxide-releasing peptide hydrogel patch. Adv. Funct. Mater. 28, 1803051 (2018).
Liang, W. et al. Conductive hydrogen sulfide-releasing hydrogel encapsulating ADSCs for myocardial infarction treatment. ACS Appl. Mater. Interfaces 11, 14619–14629 (2019).
Google Scholar
Shiekh, P. A., Singh, A. & Kumar, A. Oxygen releasing antioxidant cryogel scaffolds with sustained oxygen delivery for tissue engineering applications. ACS Appl. Mater. Interfaces 10, 18458–18469 (2018).
Google Scholar

