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

Hu, Wei; Yang, Cui; Guo, Xiaodan; Wu, Yihong; Loh, Xian Jun; Liu, Yupeng; Wu, Yun; Wu, Caisheng

doi:10.3390/gels8070423

Cited by 15 publications

(8 citation statements)

References 204 publications

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“…128 In addition, hydrogel injection alone can reduce oxidative stress, increase myocardial conductivity, and inhibit metalloproteinase-induced malignant remodeling, thereby treating cardiovascular disease. 129 Exosomes or hydrogels alone have been administered to treat cardiovascular diseases with good therapeutic effects. In practical application, exosome is primarily administered intravenously.…”

Section: Combination Therapymentioning

confidence: 99%

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels

Shi,

Zhou,

Yin

et al. 2024

IJN

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Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cellderived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.

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Section: Combination Therapymentioning

confidence: 99%

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels

Shi,

Zhou,

Yin

et al. 2024

IJN

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“…Current treatments for MI include pharmaceutical therapy, medical device implants, and organ transplants; however, each has its own inherent limitations. − Injectable hydrogels have emerged as a promising translational therapeutic toward regeneration of cardiac tissue after MI. These hydrogels have the capacity to encapsulate cells and/or locally release therapeutics after injection through a syringe or catheter. , Several formulations for injection into cardiac tissue have been demonstrated as safe in animals and are in clinical trials. , Recent hydrogels engineered for cardiac tissue to reverse the adverse myocardial microenvironment include matrix metalloproteinase-responsive hydrogels, reactive oxygen species-scavenging hydrogels, and immunomodulatory hydrogels .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Tyrosine Kinase Inhibitors Loaded Injectable Hydrogels for Improving Connexin43 Gap Junction Intercellular Communication

Zheng,

Shi,

Liu

et al. 2024

ACS Appl. Mater. Interfaces

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Myocardial infarction (MI) is one of the leading causes of death in the developed world, and the loss of cardiomyocytes plays a critical role in the pathogenesis of heart failure. Implicated in this process is a decrease in gap junction intercellular communication due to remodeling of Connexin43 (Cx43). We previously identified that intraperitoneal injection of the Pyk2 inhibitor PF4618433 reduced infarct size, maintained Cx43 at the intercalated disc in left ventricle hypertrophic myocytes, and improved cardiac function in an MI animal model of heart failure. With the emergence of injectable hydrogels as a therapeutic toward the regeneration of cardiac tissue after MI, here, we provide proof of concept that the release of tyrosine kinase inhibitors from hydrogels could have beneficial effects on cardiomyocytes. We developed an injectable hydrogel consisting of thiolated hyaluronic acid and P123-maleimide micelles that can incorporate PF4618433 as well as the Src inhibitor Saracatinib and achieved sustained release (of note, Src activates Pyk2). Using neonatal rat ventricular myocytes in the presence of a phorbol ester, endothelin-1, or phenylephrine to stimulate cardiac hypertrophy, the release of PF4618433 from the hydrogel had the same ability to decrease Cx43 tyrosine phosphorylation and maintain Cx43 localization at the plasma membrane as when directly added to the growth media. Additional beneficial effects included decreases in apoptosis, the hypertrophic marker atrial natriuretic peptide (ANP), and serine kinases upregulated in hypertrophy. Finally, the presence of both PF4618433 and Saracatinib further decreased the level of ANP and apoptosis than each inhibitor alone, suggesting that a combinatorial approach may be most beneficial. These findings provide the groundwork to test if tyrosine kinase inhibitor release from hydrogels will have a beneficial effect in an animal model of MI-induced heart failure.

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“…The injection of natural or synthetic hydrogel materials into the ventricular wall has become an excellent therapeutic strategy to break the stress feedback pathway, as it reduces the stress load on the ventricular wall by increasing the thickness of the ventricular wall and reshaping the left ventricular geometry, providing mechanical support to the myocardial area and promoting myocardial tissue repair ( 9 - 13 ). A clinical trial of alginate-hydrogel injection treatment was shown to have a good therapeutic effect and the therapeutic potential to inhibit the damage process after MI, and the safety of hydrogel materials injection has also been validated in several clinical trials ( 14 - 18 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis revealed the new mechanism of the intra-myocardial injectable alginate-hydrogel in the treatment of ventricular function degradation

Wang,

Zhou,

et al. 2024

J Thorac Dis

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Background Myocardial infarction (MI) is one of the most lethal cardiovascular diseases. The loss of cardiomyocytes and the degradation of the extracellular matrix leads to high ventricular wall stress, which further drives the pathological thinning of the ventricular wall during MI. Injecting biomaterials to thicken the infarct ventricular wall provides mechanical support, thereby inhibiting the continued expansion of the heart. As an injectable biomaterial, alginate hydrogel has achieved exciting results in clinical trials, but further research needs to be conducted to determine whether it can improve cardiac function in addition to providing mechanical support. This study sought to explore these mechanisms in an animal model of MI. Methods A MI model was established in male C57BL/6J mice by ligation of the proximal left anterior descending (LAD) coronary artery. Intramyocardial injections (hydrogel or saline group) were performed in the proximal wall regions bordering the infarct area (with one 20-µL injection). Four weeks after MI, RNA sequencing revealed that 342 messenger RNAs (mRNAs) from the infarcted hearts were differentially expressed between the saline group and hydrogel group. We subsequently conducted a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to analyze the RNA sequencing data. In addition, we employed both western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) techniques to verify a number of genes that were differentially expressed and could potentially affect cardiac function after MI. Subsequently, we confirmed these findings through in vitro experiments. Results We found that compared with hydrogel treatment group, 250 mRNAs were upregulated and 92 mRNAs were downregulated in saline group (P<0.05). And by exploring the GO and KEGG signaling pathways as well as the protein-protein interaction (PPI) network, we found that administration of alginate hydrogel modulated cardiomyocyte inflammation-associated proteins as well as chemokine-related proteins during the inflammatory response phase after MI. In addition, our analysis at both the protein and RNA level revealed that B2M was effective in improving cardiac function after MI in the hydrogel treatment group, which was consistent in the myocardium oxygen and glucose deprivation (OGD) injury model. Conclusions We explored the transcriptome changes of infarcted hearts after alginate-hydrogel injection during the inflammatory response period. Our findings suggest that the injectable hydrogel directly alters the inflammatory response and the chemokine-mediated signaling pathway of cardiomyocytes, ultimately improving cardiac function.

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

Cited by 15 publications

References 204 publications

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels

Evaluation of Tyrosine Kinase Inhibitors Loaded Injectable Hydrogels for Improving Connexin43 Gap Junction Intercellular Communication

Transcriptome analysis revealed the new mechanism of the intra-myocardial injectable alginate-hydrogel in the treatment of ventricular function degradation

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