Research Advances of Injectable Functional Hydrogel Materials in the Treatment of Myocardial Infarction

Abstract

Myocardial infarction (MI) has become one of the serious diseases threatening human life and health. However, traditional treatment methods for MI have some limitations, such as irreversible myocardial necrosis and cardiac dysfunction. Fortunately, recent endeavors have shown that hydrogel materials can effectively prevent negative remodeling of the heart and improve the heart function and long-term prognosis of patients with MI due to their good biocompatibility, mechanical properties, and electrical conductivity. Therefore, this review aims to summarize the research progress of injectable hydrogel in the treatment of MI in recent years and to introduce the rational design of injectable hydrogels in myocardial repair. Finally, the potential challenges and perspectives of injectable hydrogel in this field will be discussed, in order to provide theoretical guidance for the development of new and effective treatment strategies for MI.

Keywords: drug; genes; growth factor; hydrogel; myocardial infarction; stem cells.

Figure 1

Schematic summary of injectable functional hydrogel materials for the treatment of myocardial infarction.

Figure 2

Biological progression after myocardial infarction.

Figure 3

(a) Effect of CSCl-RoY hydrogel on the Akt and ERK signal transduction pathways. (Reprinted with permission from Ref. [57]. 2015, American Chemical Society). (b) Generation of a polypyrrole-chitosan hydrogel [58]. (c) Intra-myocardial injection of PPy: CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo [58]. (d) The chemical structures of peptides and their hydrogelation by co-assembly. (Reprinted with permission from Ref. [59]. 2022, Elsevier). (e) The process to prepare the ROS-scavenging/conductive composite hydrogel. (Reprinted with permission from Ref. [59]. 2022, Elsevier). (f) The illustration of the ROS-scavenging/conductive composite hydrogel to repair myocardial infarction. (Reprinted with permission from Ref. [59]. 2022, Elsevier).

Figure 4

(a) Scheme of mesenchymal stem cells-loaded ROS-scavenging and O₂-generating hydrogel (MSC/RCGel) for MI treatment. (b) Representative echocardiography images, and quantitative analysis of (c) left ventricular ejection fraction (LVEF), (d) left ventricular fractional shortening (LVFS), (e) left ventricular end diastolic diameter (LVIDd) and (f) left ventricular end systolic diameter (LVIDs) before MI (baseline), three days and 28 days after MI. (g) Representative Masson’s trichrome staining images in five different sections from the apex to the bottom of the heart 28 days after MI. (h) Quantitative analysis of the infarcted size. (Reprinted with permission from Ref. [106]. 2022, Elsevier). Level of significance (*—p < 0.05, **—p < 0.01, ***—p < 0.001).

Figure 5

(a) Hydrogel-loaded BMP9 and VEGF in the treatment of myocardial infarction [159]. (b) Schematic of the preparation process of the composite hydrogel [159]. (c) Assessment of fibrosis in the infarct area 28 days post-MI and quantitative analysis of the infarction size as expressed by the ratio of infarct area to total left ventricular area. (A–F) Representative images of infarcted sections performed by Masson’s trichrome staining. (A) Sham, (B) PBS, (C) Gel, (D) Gel + B/SF, (E) Gel + V, (F) Gel + B/SF + V. (G) Quantitative analysis of the infarction size as expressed by the ratio of infarct area to total left ventricular area. [159]. (d) (A) Fibrin-specific nanogel design. (B) drug-loading FSNs bind to fibrin at the site of infarction, releasing fibrinolytic drugs and small molecule cell contractile inhibitors to alleviate cardiac fibrosis (Reprinted with permission from Ref. [160]. 2018, American Chemical Society). Level of significance (***—p < 0.001, NS—not significant).

Figure 6

(a) Schematic diagram of an injectable conductive hydrogel loaded with plasmid DNA-eNOs nanoparticles and ADSCs for treatment of myocardial infarction. In this design, (1) the conductive hydrogels would enhance the electrical communications to restore the heart functions; (2) ADSCs encapsulated in hydrogels can be directly injected into the infarcted myocardium to alleviate the inflammation environment and compensate the cell loss after MI; (3) the up-regulated eNOs expression in myocardium tissue would promote neo-vascularization and enhance the mature of myocardium. (b) Cardiac structures in the six groups as revealed by Masson’s trichrome straining and quantitative analysis of fibrosis area (c), infarct size (d), and LV thickness (e). (1) Normal; (2) MI; (3) PEG-4A/HA-SH; (4) TA-PEG/HA-SH; (5) TA-PEG/HA-SH/ADSCs; (6) TA-PEG/HA-SH/ADSCs/Gene; (Reprinted with permission from Ref. [196]. 2022, Elsevier).