Elastomeric cardiopatch scaffold for myocardial repair and ventricular support

Abstract

OBJECTIVES Prevention of postischaemic ventricular dilatation progressing towards pathological remodelling is necessary to decrease ventricular wall deterioration. Myocardial tissue engineering may play a therapeutic role due to its capacity to replace the extracellular matrix, thereby creating niches for cell homing. In this experimental animal study, a biomimetic cardiopatch was created with elastomeric scaffolds and nanotechnologies. METHODS In an experimental animal study in 18 sheep, a cardiopatch was created with adipose tissue-derived progenitor cells seeded into an engineered bioimplant consisting of 3-dimensional bioabsorbable polycaprolactone scaffolds filled with a peptide hydrogel (PuraMatrix™). This patch was then transplanted to cover infarcted myocardium. Non-absorbable poly(ethyl) acrylate polymer scaffolds were used as controls. RESULTS Fifteen sheep were followed with ultrasound scans at 6 months, including echocardiography scans, tissue Doppler and spectral flow analysis and speckle-tracking imaging, which showed a reduction in longitudinal left ventricular deformation in the cardiopatch-treated group. Magnetic resonance imaging (late gadolinium enhancement) showed reduction of infarct size relative to left ventricular mass in the cardiopatch group versus the controls. Histopathological analysis at 6 months showed that the cardiopatch was fully anchored and integrated to the infarct area with minimal fibrosis interface, thereby promoting angiogenesis and migration of adipose tissue-derived progenitor cells to surrounding tissues. CONCLUSIONS This study shows the feasibility and effectiveness of a cardiopatch grafted onto myocardial infarction scars in an experimental animal model. This treatment decreased fibrosis, limited infarct scar expansion and reduced postischaemic ventricular deformity. A capillary network developed between our scaffold and the heart. The elastomeric cardiopatch seems to have a positive impact on ventricular remodelling and performance in patients with heart failure.

Cardiac Regeneration: the Heart of the Issue

“…This 3D poly-(ethylene glycol) diacrylate (PEGDA)based scaffold obtained by micro-stereolithography promoted human cardiac progenitor cell 3D spatial orientation and activation of the expression of α-sarcomeric actinin and connexin 43 [44•]. As a further example, a cardiopatch manufactured using porous elastomeric polycaprolactone (PCL) 3D membrane filled with self-assembling peptide hydrogel and seeded with autologous adipose tissue-derived progenitor cells improves myocardial infarct scars in sheep [45].…”

Recent Applications of Three Dimensional Printing in Cardiovascular Medicine

“…This positive chamber remodeling should contribute to improve diastolic filling and myocardial conditions by angiogenic, antiapoptotic and regenerative mechanisms. Preclinical studies in 18 sheep demonstrated that a cardiopatch manufactured using porous elastomeric polycaprolactone (PCL) 3D membrane filled with peptide hydrogel and stem cells improves myocardial infarct scars [71]. PCL elastomer was chosen for its good mechanical properties, namely flexibility and adaptation to curved surfaces, such as those of ventricles.…”

Transplantation of a 3D Bioprinted Patch in a Murine Model of Myocardial Infarction

“…Before translation to human trials can occur, preclinical animal studies are needed. Preclinical in vivo models pursuing regeneration of the myocardium have been reported in pigs 5 , sheep 14 , rats 6 and mice 4 . A common model of myocardial infarction (MI) in mice uses permanent ligation of the left anterior descending (LAD) coronary artery 15 , 16 .…”

“…While large animals still represent a more clinically relevant model to test cardiac regenerative properties 5 , 14 , the versatility and feasibility of the mouse model lends itself to this fast-moving area of study. This may avoid some of the pitfalls typical of large animal studies, including (but not limited to): 1) high animal mortality (unless diagonal coronary arteries are ligated leading to unpredictable segmental infarcts 14 , or the distal end of the LAD is occluded followed by reperfusion instead of permanent ligation 5 ); 2) ethical issues with the relatively increased harm caused by large animal protocols compared to mice 18 ; 3) increased cost and/or feasibility issues, for instance the relative unavailability of large animal equipment such as MRI scanners 14 . It is also important to consider that given the extensive duration and commitment typical of large animal studies, they have the potential to become outdated before they are finished, especially with the rapid developments typical of this field.…”

“…It also typically allows for a higher number of animals than large animal models in a smaller space, which permits robust comparison of multiple experimental groups, particularly useful for multiple group comparison in vivo. On the other hand, this protocol has the disadvantages that: 1) the mouse model is more distant from human heart size, anatomy and physiology than in large animal models and it does not directly translate into humans; 2) the murine LAD branches proximally, with significant variability between individual mice, which leads to infarct size variability (a problem shared with large animal models); 3) the patch must be applied over the whole anterior heart surface, which is less precise than applying over a specific infarct area; and 4) the patch is applied immediately at the time of MI (for human use it is likely to be more clinically useful to develop a patch for application to the chronically infarcted failing heart months following the initial MI 14…”