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Biomolecules ; 10(2)2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019267

RESUMO

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.


Assuntos
Hidrogéis/química , Infarto do Miocárdio/tratamento farmacológico , Peptídeos/química , Animais , Materiais Biocompatíveis/farmacologia , Células da Medula Óssea/citologia , Sistema Livre de Células , Embrião de Galinha , Inflamação , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos , Miócitos Cardíacos/citologia , Neovascularização Fisiológica , Ratos , Ratos Sprague-Dawley , Volume Sistólico/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
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