Physiologically inspired cardiac scaffolds for tailoredin vivofunction and heart regeneration

Abstract

Tissue engineering is well suited for the treatment of cardiac disease due to the limited regenerative capacity of native cardiac tissue and the loss of function associated with endemic cardiac pathologies, such as myocardial infarction and congenital heart defects. However, the physiological complexity of the myocardium imposes extensive requirements on tissue therapies intended for these applications. In recent years, the field of cardiac tissue engineering has been characterized by great innovation and diversity in the fabrication of engineered tissue scaffolds for cardiac repair and regeneration to address these problems. From early approaches that attempted only to deliver cardiac cells in a hydrogel vessel, significant progress has been made in understanding the role of each major component of cardiac living tissue constructs (namely cells, scaffolds, and signaling mechanisms) as they relate to mechanical, biological, and electrical in vivo performance. This improved insight, accompanied by modern material science techniques, allows for the informed development of complex scaffold materials that are optimally designed for cardiac applications. This review provides a background on cardiac physiology as it relates to critical cardiac scaffold characteristics, the degree to which common cardiac scaffold materials fulfill these criteria, and finally an overview of recent in vivo studies that have employed this type of approach.

Comparison of physical and biological properties of CardioCel® with commonly used bioscaffolds

“…The in vivo examination of the CardioCel explants displayed extractable calcium levels comparable with the non-GA-crosslinked PhotoFix at 6 and 12 weeks (0.45 and 0.44 mg/mg tissue, respectively, 12 weeks), mirroring previous findings [9,12,20]. The highest extractable calcium levels were recorded for the 0.6% GA-fixed BP (means of 0.57 and 0.85 mg/mg tissue for XenoLogiX and PeriGuard, respectively, 12 weeks), but a longer study may be needed to uncover greater differences in calcification potential.…”

“…Stiffening of the extracellular matrix has also been shown previously for PeriGuard compared with the untreated tissue [15,19]. The lack of pliability of these materials may affect their performance in vivo, as stiffness can affect compliance, and the differences between the mechanical properties of aortic tissues and replacement materials can have unwanted haemodynamic effects leading to graft failure and can even affect the phenotype of cells binding to the bioscaffolds [20].…”

Cells, Scaffolds and Their Interactions in Myocardial Tissue Regeneration

“…Formation of vascularized functional heart engineered tissue is the key determining factor in cardiac tissue engineering efficacy [Bursac, ]. It has been shown that interaction of cells with scaffold components through promoting the various signaling pathways can control the cells survival as well as stem cells proliferation, differentiation, and also formation of functional tissue [Kaiser and Coulombe, ]. Currently, the combination of several growth factors with scaffolds such as VEGF, b‐FGF, PDGFBB [Lin et al, ; Lisi et al, ; Matsuda et al, ] and IGF‐1 [Karam et al, ] is known to be an appropriate method for regulating the engineered tissue microenvironment and also for controlling the survival of the cells, and their differentiation.…”

Biomaterials for cardiac tissue engineering

“…Once the cells are injected or placed with a biomaterial matrix at the desired site in the heart, their fate needs to be tracked in vivo and this special section brings an original paper on in vivo tracking of angiogenic cells transplanted into rodent hearts [14]. Finally, the progress of in vivo pre-clinical studies with engineered cardiac tissues on biomaterial matrices are reviewed [15]. …”