A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction.

Saman Firoozi,Sara Pahlavan,Mohammad-Hossein Ghanian,Shahram Rabbani,Shima Tavakol,Maryam Barekat,Saeed Yakhkeshi,Elena Mahmoudi,Mansoureh Soleymani,Hossein Baharvand

doi:10.3390/biom10020205

Abstract

Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation.

Highlights

Myocardial infarction (MI) is the most prevalent among cardiac disorders and has high morbidity and mortality rates [1]
To investigate the cell encapsulation potential of the Self-assembling peptide (SAP) hydrogel, Neonatal Mouse Cardiomyocytes (NMCMs) were mixed with the (RADA)4-SDKP solution followed by calcium ion addition to enable the mixture to gel
The metabolic activity of the encapsulated NMCMs within the (RADA)4-SDKP hydrogel was assessed by MTS assay

Summary

Introduction

Myocardial infarction (MI) is the most prevalent among cardiac disorders and has high morbidity and mortality rates [1]. Conventional therapeutic approaches for MI have been developed based on revascularization by different means such as balloon angioplasty or coronary artery bypass grafting [6]. Mostly successful, these revascularization methods could not fully inhibit ventricular remodeling due to hypoxia in the infarct area. Cardiac cell therapy has shown partial success, which is likely due to low engraftment of the transplanted cells [12,13] Both viability and retention of the transplanted cells could be hampered by insufficient nutrition caused by lack of vasculature, inflammatory conditions, and remodeled ECM in the fibrotic area [14]

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Results

Conclusion