Injectable Hydrogel Helps Bone Marrow-Derived Mononuclear Cells Restore Infarcted Myocardium

Abstract

Backgrounds: Experimental and clinical studies have suggested that cell implantation could improve cardiac function after myocardial infarction (MI). However, this technique was limited by decreased engraftment and survival of transplanted cells within the ischemic tissue. The present study was performed to investigate whether implantation of bone marrow-derived mononuclear cells (BMMNCs) encapsulated in hydrogel could increase cell engraftment and help to restore cardiac function of MI rabbits. Methods: MI was induced in rabbits by coronary artery ligation. One week later, cell culture medium, Dex-PCL-HEMA/PNIPAAm hydrogel, BMMNCs in medium or BMMNCs in hydrogel were injected into the infarcted area of the left ventricle (LV). Results: Increased cell engraftment was observed 48 h after injection when cells were encapsulated in hydrogel; 30 days after treatment, echocardiographic studies showed that injection of BMMNCs in hydrogel preserved LV ejection fraction and attenuated LV dilatation compared with other groups. Histological analysis indicated that injection of BMMNCs in hydrogel enhanced neovascular formation and prevented scar expansion compared with the other groups. Conclusion: Injection of hydrogel-encapsulated BMMNCs increased cell engraftment and improved LV function; this technique may serve as an effective approach to restore infarcted myocardium.

Understanding greater cardiomyocyte functions on aligned compared to random carbon nanofibers in PLGA

“…There has been considerable interest in developing injectable scaffolds (such as poly(N-isopropylacrylamide) [PNIPAAM], collagen, or helical rosette nanotubes), which offer the advantage of avoiding patient-specific scaffold 90 asiri et al prefabrication and highly invasive surgery. 6 PNIPAAM has indeed improved cardiac functions in rabbit infarct models, preserving left ventricle ejection and preventing scar tissue formation, 7,8 while collagen has thickened the infarcted wall and enhanced angiogenesis. 9,10 However, noninjectable cardiac patches also have their own distinct advantages, because with injectables, one has to be concerned with developing materials with quick solidification times to avoid permeation of the injectable throughout the body (which could cause toxic responses).…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…A significant increase in cell engraftment 48 h after injection compared to free SC administration was observed. One month after treatment significant LV-EF preservation and attenuated LV dilatation accompanied by enhanced neovascular formation and prevented scar expansion were found in BMSC-hydrogel group compared to the rest of the groups [53].…”

Stem Cell Engineering for Cardiac Tissue Regeneration

“…There was no difference in vascular density bordering the infarct zone between the control and hydrogel-alone groups; however, microvessels labeled with ␣ -smooth muscle actin in the infarct area were greater after hydrogel plus cell administration than after cell injection alone. Most strikingly, Li et al [3] also found that the injection of hydrogel alone significantly attenuated left ventricular infarct size and improved cardiac function compared with control, suggesting that the hydrogel may be capable of preventing left ventricular remodeling by increasing regional wall stiffness through the preservation of wall thickness. These results are consistent with previous observations that injection of either fibrin glue or collagen alone reduces infarct size compared with injection of control bovine serum [4,5] .…”

“…In the study by Li et al [3] in this issue of Cardiology , Dex-PCL-HEMA/PNIPAAm hydrogel, a temperatureresponsive biomaterial synthesized by specific polymers that are composed of a hydrophobic poly -caprolactone-2-hydroxylethyl methacrylate (PCL-HEMA) chain and a poly N-isopropylacrylamide (PNIPAAm) chain, were delivered into the injured heart in combination with bone marrow stem cell transplantation. A unique feature of this synthetic biomaterial for tissue engineering is that it Yoshida /Oh Cardiology 2010;115:191-193 192 farct scar, a phenomenon not seen with the synthetic hydrogel used in this study.…”

“…On the other hand, the combination of natural and synthetic biomaterials may provide a novel approach to resolve the problems associated with the mechanical properties unique to each. In this context, it is noteworthy that Li et al [3] also attempted to combine PCL with PNIPAAm, although both are synthetic polymers, to produce a potentially stable cardiac tissue in situ. A critical question that will need to be resolved with such combinations is whether such polymers will cause diastolic dysfunction after cardiac implantation, and how to prevent this development.…”