An overview of recent flexible- and soft-biomaterial applications in myocardial infarction and other cardiovascular diseases

Figures

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  Fig. 1. Thermoplastic and elastomeric polymers employed in cardiovascular applications. A) Deformed microstructures of fiber scaffolds fabricated from polycaprolactone (PCL) via melt electrowriting (MEW), at different strain levels (ε) (top row), together with application and shape recovery of the scaffolds on a porcine heart (bottom row). B) Shape retention of poly(lactic-co-ε-caprolactone) (PLCL) vascular grafts (top row) and permanent deformation of PCL grafts (bottom row) upon removal of external forces applied by tweezers. C) Fabrication method of biodegradable poly(L-lactic acid) (PLLA) tubular stents via a mandrel-based 3D printing technique (top row) and the corresponding result (bottom row). D) Scanning electron microscopy images of poly(glycerol sebacate) (PGS)-based vascular grafts (TEVG) with braided polyglycolic acid (PGA). Figures adapted with permission from: A) [74]; B) [103]; C) [150]; D) [144].

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  Fig. 2. Thermoplastic and elastomeric polymers employed in cardiovascular applications. A) Working mechanisms of ROS-responsive polyurethane (PFTU) and its electrospun epicardial patch (PFTU/Gt) for MI treatment in vivo. B) Fabrication procedure of poly(lactic acid) (PLA):PGS scaffolds for cardiac tissue engineering (TE) with increased hydrophilicity, flexibility, and ease of functionalization. C) Top row: scanning electron microscopy image of the fibrous microstructure of a polycarbonate (PC) bis-urea valve (scale bar: 50 μm) and working mechanism; bottom row: video frames of an in vitro valve functionality test highlighting proper closure and opening. D) Manufacturing diagram of conductive elastic cardiac patches made of poly(γ-methyl-Ɛ-capro-lactone)-b-poly(ε-caprolactone)-PEG-poly(ε-caprolactone)-b-poly(γ-methyl-ε-caprolactone) (PMECL). Figures adapted with permission from: A) [165]; B) [148]; C) [71]; D) [122].

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  Fig. 3. Cardiovascular uses of traditional hydrogels. A) Intramyocardial injection of a peptide (7Ap)-loaded collagen I to an infarcted region and all the effects (stem cell recruitment, angiogenesis, LV wall remodeling) that synergistically led to overall functional recovery. B) Schematic illustration of drug loading onto conductive branched polyethyleneimine (bPEI)-coated gold (Au) nanoparticles (bPEI-AuNPs), incorporation into collagen hydrogel, and subsequent drug release. C) Fabrication process via polydimethylsiloxane (PDMS) molds of gelatin hydrogels containing graphene oxide (GO), exhibiting micropatterns. D) Illustration of the photocrosslinking mechanism of gelatin methacryloyl (GelMA) from a precursor solution to a hydrogel via the UV irradiation (1) and a schematic depicting the in-situ polymerization linking following intramyocardial injection (2). Figures adapted with permission from: A) [183]; B) [184]; C) [205]; D) [18].

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  Fig. 4. Cardiovascular uses of traditional hydrogels. A) Visualization of alginate microspheres, subsequent loading with vascular endothelial growth factor (VEGF), and compaction into a calcium-alginate microsphere patch, and application of the patch and of the restraining chitosan sheet to rat infarcted regions. B) Schematic of thiolene photopolymerization chemistry used to crosslink 8-arm polyethylene glycol (PEG)-norbornene with a matrix metalloproteinase (MMP)-degradable peptide and to incorporate CRGDS cell adhesion peptide. C) Illustration of the synthesis of conductive PEG-based hydrogels, starting from the UV polymerization of diacrylated PEG (PEGDA) containing polystyrene sulfonate (PSS), with subsequent inclusion and polymerization of poly(3,4-ethylenedioxythiophene (PEDOT), and resulting in a semi-interpenetrating network. D) Sketch of the composition and structure of a conductive thiol-modified hyaluronic acid (HA-SH) crosslinked with a multi-armed PEGDA-Melamine (PEG-MEL) crosslinker, employed for cell delivery via injection onto infarcted areas of rats. Figures adapted with permission from: A) [21]; B) [213]; C) [223]; D) [237].

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  Fig. 5. Applications in the cardiovascular field of hybrid materials. A) Structural characteristics of scaffolds composed of carbon nanotubes (CNTs) embedded poly(glycerol sebacate):gelatin (PG) electrospun nanofibers, showing the interactions of CNTs with PG upon cross-linking with EDC/NHS. B) CAD representation of the automated Rotary Jet Spinning system to manufacture hybrid valves composed of poly-4-hydroxybutyrate and gelatin. C) Representation of extrusion-based printing into melt-electrowritten meshes to create a patterned pre-vascularized myocardial construct, employing gelatin methacryloyl (GelMA) and collagen for the myocardial component (pink area) and GelMA, collagen, and fibrinogen for the vascular fraction (purple area). D) Scheme composition of vascular grafts composed of poly(ε-caprolactone) (PCL) and methacryloyl gelatin-alginate (GEAL), fabricated via a combination of solution blow spinning (PCL) and dip coating/photo-crosslinking (GEAL). Figures adapted with permission from: A) [261]; B) [262]; C) [263]; D) [264].

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  Fig. 6. Applications in the cardiovascular field of hybrid materials. A) Representation of the fabrication process of cardiac patches consisting of an electrospun PCL membrane, a crosslinked fibrin coating, and an additional coating layer of alginate. B) Preparation schematic of collagen-alginate gels for the treatment of heart failure, rendered electroactive by the incorporation of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS). C) Illustration of the synthesis of conductive cardiac patches, consisting of poly(glycerol sebacate) (PGS), collagen I, and polypyrrole (PPy). Figures adapted with permission from: A) [49]; B) [17]; C) [272].

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  Fig. 7. Smart materials employed in cardiovascular applications. A) Schematic of the working principle of a thermosensitive sodium hyaluronate/sodium alginate solution, rapidly changing from liquid to hydrogel at 37 °C due to the crosslinking between sodium alginate and the Ca2+ released from DPPC/DMPC liposomes (1: room temperature; 2: body temperature). B) The fabrication of an intramyocardial delivery system of the anti-inflammatory colchicine, based on an injectable and thermosensitive poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel, which exhibits a reversible sol-gel transition. C) Molecular sketch of ureido-pyrimidinone stacks (red) surrounded by a PEG corona (blue) (1), fiber alignment and crosslinking (2), assembling into transient networks. D) Design of poly(N-isopropyl acrylamide) (PNIPAAm)-based hydrogels with pH sensitivity at body temperature, exhibiting a reversible change in hydrophilicity. Figures adapted with permission from: A) [293]; B) [292]; C) [307]; D) [298].

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  Fig. 8. Smart materials employed in cardiovascular applications. A) Illustration of the design of an injectable ROS-sensitive hyperbranched poly(β-amino esters) (HB-PBAE) hydrogel, in-situ crosslinked with thiolated hyaluronic acid (HA-SH) and entrapping polydopamine (PDA)-covered tanshinone IIA (TIIA) nanoparticles (TIIA@PDA NPs). B) Schematic of the structure of a polyvinyl alcohol (PVA) hydrogel crosslinked with the ROS-sensitive TSPBA to deliver basic fibroblast growth factor (bFGF) upon injection into the pericardial cavity. C) Illustration of the structure and working mechanisms of the smart Janus adhesive CPAMC/PCA hydrogel as a cardiac patch, which can be on-demand removed by exposure to GSH. Figures adapted with permission from: A) [301]; B) [308]; C) [302].