Bioresorbable Polymeric Scaffold in Cardiovascular Applications

Abstract

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6-8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript.

Keywords: biomaterials; bioresorbable scaffolds; cardiac patches; cardiovascular tissue engineering; polymeric scaffolds; vascular grafts.

Figure 1

Degradation of aliphatic polylactic acid (PLA). (a) Hydrolysis of ester bond. (b) Illustration of the loss of device’s radial strength (starts at 6 months), loss of mass (12 months) and molecular weight with time. The complete degradation of BRS is expected to be at 24 months mark [35]. Image adapted from [35].

Figure 2

BRS fabrication techniques by (a) extrusion and passing the melted polymer through a solid mandrel; (b) dip coating of the mandrel in a polymer solution, (c) melt spinning and drawing of fibre in aligned orientation and (d) fused deposition method (FDM) to deposit material according to the CAD input. Images adapted from [39,40,41].

Figure 3

BRS in development, the preclinical or clinical phase. (a) Abbott Vascular’s ABSORB BVS 1.1, (b) Arterial Remodelling Technologies’ ART18Z (2nd generation), (c) Bioabsorbable Therapeutics Inc’s (BTI) stent, (d) Arterius’ ArterioSorb, (e) REVA Medical’s Fantom, (f) Elixir Medical’s DESolve, (g) Manli Cardiology’s MIRAGE, (h) HuaAn Biotech’s Xinsorb, (i) Amaranth’s Fortitude, (j) Igaki-Tamai stent, (k) REVA Medical ReZolve and (l) Meril Life Sciences’ MeRes100 [32,44,53,54].

Figure 4

The process of producing a tissue engineered vascular graft through scaffold-based method. The patient’s cells are harvested, then isolated and cultured in vitro before seeded into a scaffold or mixed together with a polymer scaffold material in a tubular mould. Additional conditioning and culturing in a bioreactor is required. Image adapted from [66].

Figure 5

Schematic illustrating methods for scaffold fabrication. (a) Electrospinning of mesh onto rotating mandrel, (b) Introducing blowing agent with temperature in the process of gas foaming, (c) solvent casting followed by particulate leaching and (d) emulsion freeze drying to form porous scaffolds. Image adapted from [97].

Figure 6

Brief history of TE products leading up to cardiac patches conceptualisation. Adapted from [134].

Figure 7

Schematic of cardiac extracellular matrix.