Current advances in biodegradable synthetic polymer based cardiac patches

Abstract

The number of people affected by heart disease such as coronary artery disease and myocardial infarction increases at an alarming rate each year. Currently, the methods to treat these diseases are restricted to lifestyle change, pharmaceuticals, and eventually heart transplant if the condition is severe enough. While these treatment options are the standard for caring for patients who suffer from heart disease, limited regenerative ability of the heart restricts the effectiveness of treatment and may lead to other heart-related health problems in the future. Because of the increasing need for more effective therapeutic technologies for treating diseased heart tissue, cardiac patches are now a large focus for researchers. The cardiac patches are designed to be integrated into the patients' natural tissue to introduce mechanical support and healing to the damaged areas. As a promising alternative, synthetic biodegradable polymer based biomaterials can be easily manipulated to customize material properties, as well as possess certain desired characteristics for cardiac patch use. This comprehensive review summarizes recent works on synthetic biodegradable cardiac patches implanted into infarcted animal models. In addition, this review describes the basic requirements that should be met for cardiac patch development, and discusses the inspirations to designing new biomaterials and technologies for cardiac patches.

Keywords: biodegradable polymer; cardiac patch; heart disease; heart infarction.

FIGURE 1

Illustration to show a cardiac patch placed on an infarcted heart, and general requirements to design a biodegradable polymeric cardiac patch

FIGURE 2

(a) Chemical structure of PLGA. (b) Chemical structure of PGS. (c) Chemical Structure of PLLA. (d) Chemical structure of PCL. (e) Chemical structure of a typical biodegradable PU synthesized from PCL, 1,4-diisocyanatobutane and putrescine (Guan et al., 2002). (f) PGS fabricated with salt leaching. Reproduced with permission (Radisic, M., Park, H., Martens, T. P., Salazar-Lazaro, J. E., Geng, W., Wang, Y., … Vunjak-Novakovic, G. (2008)). Copyright 2008, published by Wiley. (g) PEUU scaffold fabricated using phase separation. Reproduced with permission (Hashizume et al., 2013). Copyright 2013, published by Elsevier Ltd. (h) Electrospun GelMA/PCL. Reproduced with permission (He et al., 2018). Copyright 2018, published by Theranostics. (i) Nanofiber phase separation scaffold of PLLA. Reproduced with permission (Liu et al., 2015). Copyright 2015, published by Elsevier Ltd. (j) PLGA film cast scaffold on patterned surface. Reproduced with permission (Cristallini et al., 2019). Copyright 2019, published by Wiley

FIGURE 3

(a) Macroscopic view and measurement of infarct size after 28 days post-implantation into mice. The yellow dashed line indicates the area of ventricle aneurysms. Yellow arrows point to new blood vessel branches. (b) 2,3,5-Triphenyltetrazolium chloride (TTC) staining performed on the mice groups 28 days after transplantation. Red staining denoted healthy myocardium and white staining represents the infarcted area. (c) Topography of natural proteins (elastin and collagen)/PCL electrospun sheets via scanning electron microscopy (SEM). Reprinted with permission (Liu et al., 2016). Copyright 2016, published by e-Century Publishing Corporation

FIGURE 4

(a) Scaffold cross-section electron micrograph images from PEUU, PECUU, and PCUU, respectively. Scaffolds were prepared using salt-leeching method. (b) Macroscopic images of rat heart implant sites for PEUU, PECUU, and PCUU scaffolds and their trans-sectional views at 16 weeks post-MI. (c) Representative views of Masson’s trichrome stained cross-sections of mouse hearts at 16 weeks post-MI for PEUU, PECUU, and PCUU scaffolds, where black boxes indicate the area shown in higher magnifications in the right panels, red arrows indicate suture lines placed at the time of implantation, and black arrows indicate regions with trace amount of remaining scaffold material. Reprinted with permission (Hashizume, Hong, et al., 2013). Copyright 2013, published by Elsevier Ltd