An injectable hydrogel combining medicine and matrix with anti-inflammatory and pro-angiogenic properties for potential treatment of myocardial infarction

Abstract

One of the main illnesses that put people's health in jeopardy is myocardial infarction (MI). After MI, damaged or dead cells set off an initial inflammatory response that thins the ventricle wall and degrades the extracellular matrix. At the same time, the ischemia and hypoxic conditions resulting from MI lead to significant capillary obstruction and rupture, impairing cardiac function and reducing blood flow to the heart. Therefore, attenuating the initial inflammatory response and promoting angiogenesis are very important for the treatment of MI. Here, to reduce inflammation and promote angiogenesis in infarcted area, we report a new kind of injectable hydrogel composed of puerarin and chitosan via in situ self-assembly with simultaneous delivery of mesoporous silica nanoparticles (CHP@Si) for myocardial repair. On the one hand, puerarin degraded from CHP@Si hydrogel modulated the inflammatory response via inhibiting M1-type polarization of macrophages and expression of pro-inflammatory factors. On the other hand, silica ions and puerarin released from CHP@Si hydrogel showed synergistic activity to improve the cell viability, migration, and angiogenic gene expression of HUVECs in both conventional and oxygen/glucose-deprived environments. It suggests that this multifunctional injectable CHP@Si hydrogel with good biocompatibility may be an appropriate candidate as a bioactive material for myocardial repair post-MI.

Transplantation of Stem Cell Spheroid-Laden 3-Dimensional Patches with Bioadhesives for the Treatment of Myocardial Infarction

“…Thus, reducing the fibrotic area in the LV is important for maintaining or restoring cardiac function. MI is accompanied by ECM degradation, LV wall thinning, and ventricular enlargement [ 10 , 50 ]. Based on these, we histologically analyzed LV wall thickness, infarction size, and fibrosis area.…”

“…Furthermore, unlike other organs, the regenerative ability of the damaged heart is limited because adult cardiomyocytes have low proliferative and self-renewal capacities [ 3 , 5 – 8 ]. Conventionally, MI is treated using a combination of pharmacological and surgical interventional therapies, such as balloon angioplasty, coronary bypass, stent insertion, and heart transplantation, to enhance patient prognosis [ 2 , 8 – 10 ]. However, these therapies have not been able to be a fundamental treatment to regenerate injured myocardium with its function, and postoperative management is important to reduce infarct size [ 4 ].…”

Overview of Injectable Hydrogels for the Treatment of Myocardial Infarction

“…Neovascularization, which facilitates the provision of oxygen and nutrients to infarct areas, not only ameliorates the adverse microenvironment associated with MI and enhances the survival rate of transplanted cells, but also prevents further expansion of infarcted region [141,142]. In this context, researchers have explored the incorporation of various vascular regulatory factors [143], plasmids [9], or drugs [17,26] into injectable hydrogels to accelerate the restoration of myocardial vascularization.…”

“…This revolutionary approach offers a promising treatment option for repairing infarcted myocardium [15,16]. To improve therapeutic effects, numerous injectable hydrogels have been developed to deliver therapeutic agents [17] and cells [18] locally to areas of infarcted myocardium. Although the effectiveness of these injectable hydrogels in MI therapies has been extensively demonstrated in small animal models, adequate investigations using large animals (such as porcine models) to establish a proof of concept supporting preclinical studies of MI treatment are lacking.…”

Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies

“…Hydrogels, a set of soft materials with large among of water, which have comparable mechanical compliance to native tissues, show unique advantages in tissue engineering [ 140 , 141 ]. The three-dimensional network structure formed by hydrogels has great capacity in carrying and releasing drugs [ 142 , 143 ].…”