Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials

Abstract

Ischemic heart disease is a common cause of end-stage heart failure and has persisted as one of the main causes of end stage heart failure requiring transplantation. Maladaptive myocardial remodeling due to ischemic injury involves multiple cell types and physiologic mechanisms. Pathogenic post-infarct remodeling involves collagen deposition, chamber dilatation and ventricular dysfunction. There have been significant improvements in medication and revascularization strategies. However, despite medical optimization and opportunities to restore blood flow, physicians lack therapies that directly access and manipulate the heart to promote healthy post-infarct myocardial remodeling. Strategies are now arising that use bioactive materials to promote cardiac regeneration by promoting angiogenesis and inhibiting cardiac fibrosis; and many of these strategies leverage the unique advantage of cardiac surgery to directly visualize and manipulate the heart. Although cellular-based strategies are emerging, multiple barriers exist for clinical translation. Acellular materials have also demonstrated preclinical therapeutic potential to promote angiogenesis and attenuate fibrosis and may be able to surmount these translational barriers. Within this review we outline various acellular biomaterials and we define epicardial infarct repair and intramyocardial injection, which focus on administering bioactive materials to the cardiac epicardium and myocardium respectively to promote cardiac regeneration. In conjunction with optimized medical therapy and revascularization, these techniques show promise to upregulate pathways of cardiac regeneration to preserve heart function.

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

“…Tissues taken from living sources can undergo a decellularization process to remove all cells from its ECM. The resulting matrix is made of structural proteins such as collagen and glycosaminoglycans, and endogenous molecules [ 230 ]. In various domains such as cardiac surgery and breast reconstruction, it is used as scaffolding material.…”

“…It provides an authentic physiological microenvironment for cells to grow into a specific tissue from which the scaffold is derived [ 231 , 232 ]. Commercially available acellular matrices can also be a synthetic mixture of many ECM components from different tissue sources [ 230 ].…”

“…The biological approach is based on the use of enzymes such as collagenase, trypsin, or nuclease to remove all cells. Decellularization by physical methods includes mechanical abrasion, electroporation, and temperature and pressure treatment [ 230 ]. The objective is to remove all cellular components while preserving, as much as possible, the ECM components and structure for their excellent biomimicry properties.…”

Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries

“…It should possess tailored mechanical properties, such as anisotropy, elasticity, and contractility, to provide the required pressure for an effective pump function while withstanding the tensile stress [ 30 ]. The surface properties should be tailored with functional niches to provide the cells with anchoring positions promoting attachment, anisotropic alignment, and proliferation [ 31 ]. Thus, scaffold stiffness and geometry are important features to be considered, with square pores being more efficient in promoting cell adhesion rather than hexagonal pores [ 32 ].…”

Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery

“…The use of decellularized extracellular matrix bioscaffolds in cardiac surgery is promising, given the broad application of these bioscaffolds in cardiac structural repair and myocardial regeneration. It is increasingly apparent that the properties of each bioscaffold, including tissue source, fixation method, immunogenic properties, growth factor content, and biomechanical properties, determine its suitability for specific clinical scenarios in cardiac repairs at the time of cardiac surgery [ 7 , 8 ]. Our group’s previous work explored non-fixed acellular porcine small intestinal submucosal extracellular matrix (SIS-ECM) and its ability to influence the local cardiac microenvironment.…”