Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver

Abstract

Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy.

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

“…MMP-2 and MMP-9 are important players implicated in many cardiovascular diseases and ECM degradation [13]. They can exacerbate contractile dysfunction by degrading cardiac proteins [2]. All infarct groups showed a high level of MMP-2/9 activity (Fig.…”

“…Stem cell-related technology can provide new cardiomyocytes via direct reprogramming and paracrine signaling via cell injection. Proteins and nucleic acids can alter the composition of local signaling molecules and enhance repair and regeneration [2, 19, 20]. Tissue-engineered patches can combine cells, growth factors, and mechanical signal to provide comprehensive cues to restore structure and functions of the heart [21].…”

“…Current treatments such as reperfusion, β-blockers, and angiotensin converting enzyme inhibitors, reduce damage but do not restore function. Therefore, therapies that can prevent or reverse the multiple pathologies caused by MI, regenerate the myocardium, and restore cardiac function are urgently needed [2]. …”

“…To treat multiple pathologies resulting from MI, we set out to explore the use of multiple therapeutic proteins [2]. Our recent study using a statistical fractional factorial design of experiment focused our effort into the controlled and timed release of a combination of complementary proteins that are relatively distinct in their roles in cardiac function: tissue inhibitor of metalloproteinases 3 (TIMP-3), basic fibroblast growth factor (FGF-2), and stromal cell-derived factor 1 alpha (SDF-1α) [3].…”

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

“…1 It results in cardiomyocyte loss, myocardial remodeling, and the deterioration of cardiac function, which can eventually lead to heart failure. 2 Current therapies, including conventional pharmacological agents and left ventricular (LV) assist devices can only delay the progression of the disease, and the shortage of heart donors is also a factor for innovating new therapies. 3 Therefore, new therapies are needed to regenerate damaged hearts to overcome the poor prognosis of patients with heart failure.…”