Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair

Abstract

One of the major problems in the treatment of cardiovascular diseases is the inability of myocardium to self-regenerate. Current therapies are unable to restore the heart's function after myocardial infarction. Myocardial tissue engineering is potentially a key approach to regenerate damaged heart muscle. Myocardial patches are applied surgically, whereas injectable hydrogels provide effective minimally invasive approaches to recover functional myocardium. These hydrogels are easily administered and can be either cell free or loaded with bioactive agents and/or cardiac stem cells, which may apply paracrine effects. The aim of this review is to investigate the advantages and disadvantages of injectable stem cell-laden hydrogels and highlight their potential applications for myocardium repair.

Opinion on the recent development of injectable biomaterials for treating myocardial infarction

“…However, the selection on the modulus of the hydrogel systems from MPa to Pa level is significantly different in various research reports. It is a general belief that hydrogels should possess mechanical properties comparable to that of the native myocardium to provide adequate mechanical support to the infarcted myocardium [5]. However, in our latest research, we found that injectable biomaterials in vitro applications can have a very low stiffness (25 Pa), and a significant improvement of heart functions (ejection fraction and infarction size) was achieved, which is comparable to the other reports with much stiffer hydrogels.…”

“…A longer remaining period may hinder repair process. It should be noted that there is still much debate as to the mechanical and degradation properties of injectable materials applied for MI, due to the large disparity between different research reports [2,5].…”

“…In general, the contribution of stem cells to myocardial restoration is believed to work by two independent mechanisms: direct differentiation and paracrine effects. Restoration is mainly mediated by the paracrine effect, whereas direct differentiation only plays a minor role due to the fact that the most of transplanted stem cells would die within a few days in vivo [5]. Analogous to stem cell based therapy, investigations have confirmed the promotional effect of stem cells exosomes (SC-Exos) on tissue repair and regeneration, and it is believed that the exosomes induce the promotion of proliferation and the inhibition of apoptosis.…”

Looking Beyond Reperfusion

“…The transposition of a fat flap over the ischemic myocardium has recently been proposed, with promising results in the swine preclinical model of MI [82]. Tissue-engineered, hydrogel-based Mesenchymal stem cells (MSCs) [83] and endothelial progenitor cell [84] therapy have been shown some promising results in re-vascularizing the ischemic myocardium and preserving ventricular function through paracrine effects [85]. Table 3 presents recent cell based clinical trials for cell based therapies of regeneration of myocardium.…”

Photothermal-modulated drug delivery and magnetic relaxation based on collagen/poly(γ-glutamic acid) hydrogel

“…[1][2][3][4][5][6][7][8][9] By modulating the chemical or physical interactions between natural and/or synthetic polymeric materials, various types of hydrogels have been developed. [10][11][12][13][14][15] Although the chemical gelation strategy using synthetic polymers shows advantages, such as the systematic control of molecular structure and resultant hydrogel properties, toxicity issues still limit their wide adoption in clinical fields.…”