Table 3.
In vivo improvements achieved with scaffolds composed of the polysaccharides chitosan, alginate or hyaluronic acid
| Scaffold material | Cell lines and/or other components | MI model | Main results | References |
|---|---|---|---|---|
| Chitosan | Rat brown ATDSCs | Rat | Cell survival and retention↑, EF↑, FS↑, LV end-diastolic pressure↓, LV pressure change↑, infarct size↓, fibrosis↓, ATDSC to cardiac lineage differentiation↑, vessel density↑, endothelial and smooth muscle cell differentiation | [81] |
| Mouse ESCs | Rat | Infarct zone cell retention↑, ESC to cardiac differentiation, heart function↑, LV end-diastolic and end-systolic diameters↓, EF↑, FS↑, infarct size↓, wall thickness↑, complete chitosan degradation, microvessel density↑ | [82] | |
| Mouse nuclear-transferred ESCs or fertilization-derived mouse ESC | Rat | For both cell types: infarcted area covered↑, possible differentiation into CMs, smooth muscle cells and ECs, heart function↑, LV end-diastolic and end-systolic diameters↓, EF↑, FS↑, infarct size↓, wall thickness↑, complete chitosan degradation, neovascularization↑ | [83] | |
| bFGF | Rat | LV EF↑, LV FS↑, arteriole density↑, infarct size↓, fibrosis area↓ | [84] | |
| RoY peptide | Rat | Angiogenesis↑, ventricular wall thickness↑, fibrosis↓, infarct size↓, LV FS↑, LV EF↑ | [85] | |
| Chitosan+alginate | Rat MSCs | Rat | EF↑, LV function↑, angiogenesis↑ | [77] |
| – | Rat | Angiogenesis↑, no inflammation exacerbation, apoptosis↓, presence of c-kit+ cells↑, proliferation↑, wall thickness↑, LV expansion↓, LV EF↑ | [87] | |
| Alginate | – | Rat | Absence of arrhythmias or thrombus formation, scaffold degraded, scar thickness↑, diastolic and systolic anterior wall thicknesses↑, LV end-diastolic and systolic dimensions↓, LV end-diastolic and systolic areas↓, cardiac dysfunction↓ | [98] |
| – | Dog | End-systolic and end-diastolic wall thicknesses↑, LV end-diastolic and systolic volumes↓, end-systolic sphericity index↑, LV EF↑, functional mitral regurgitation↓, LV function↑ | [99] | |
| – | Pig | No arrhythmias or conduction blocks, no remote infarcts in other organs, LV enlargement↓, LV function↑, coronary blood flow not affected, scar thickness↑, anterior wall thickness↑ | [100] | |
| Rat fetal cardiac cells | Rat | Vascularization↑, formation of myofibers and gap junctions, preservation of LV dimensions and FS | [102] | |
| Human ESCs or human embryonic bodies | Rat | FS↑, LV dilation, absence of inflammation, no cardiomyogenic differentiation, no cell retention | [103] | |
| RGD peptide | Rat | FS↑, LV dimension↓, LV wall thickness↑, angiogenesis↑ | [105] | |
| RGD peptide+encapsulated MSCs (microbeads) | Rat | LV function↑, wall thickness preservation, LV internal dimensions preserved, infarct size↓, angiogenesis↑, high cell retention | [106] | |
| Unmodified alginate; RGD or YIGSR peptide-modified alginate; or RGE peptide-modified alginate | Rat | Unmodified-alginate: scar thickness↑, attenuated LV systolic and diastolic dilatations, LV FS↑, fractional area change↑, LV expansion index↓ (compared with all peptide-modified alginates) | [107] | |
| IGF/HGF (microbeads) | Rat | Scar thickness preservation, infarct expansion index↓, scar collagen accumulation↓, vascularization↑, apoptosis↓ | [110] | |
| – | Human | New York Heart Association functional class↑, Kansas City Cardiomyopathy Questionnaire score↑ | [111] | |
| Alginate+fibrin | – | Pig | LV posterior wall thickness↑, infarct expansion↓, extractable collagen↓ | [115] |
| Alginate+Matrigel+omentum | Neonatal rat cardiac cells with SDF-1, IGF-1 and VEGF | Rat | Mechanical and electrical coupling, relative scar thickness↑, angiogenesis↑, infarct expansion index↓, FS and fractional area change preserved, LV end-diastolic and systolic dimensions↓ | [117] |
| Alginate+polypyrrole | – | Rat | No inflammation, angiogenesis↑, myofibroblast population↑ | [118] |
| Hyaluronic acid | Alone or with VEGF | Rat | Ventricle thickness↑, infarct size↓, apoptosis↓, vascularization↑, heart function↑ | [121] |
| Rat BMMNCs | Rat | Apoptosis↓, inflammatory response↓, EF↑, ventricular dilatation↓, scar size↓, collagen content↓, angiogenesis↑, cell differentiation into ECs | [124] | |
| Pig BMMNCs | Pig | LV EF↑, interventricular septum thickness↑, LV end-diastolic pressure and volume↓, contractility↑, scar size and length↓, fibrosis↓, high cell retention, neovascularization↑ | [125] | |
| Rat bone marrow MSCs (esterified hyaluronic acid) | Rat | Construct integration, vascularization↑, fibrosis↓ | [126] | |
| Pig bone marrow MSCs (esterified hyaluronic acid) | Pig | Inflammation↓, fibrosis↓, degeneration of cardiac cells↓ | [127] | |
| Hydroxyethyl methacrylate, SDF-1α, mouse bone marrow cells | Mouse | Cell homing in the myocardium↑ | [128] | |
| rTIMP-3 | Pig | LV end-diastolic dimension↓, LV EF↑, wall stress↓, infarct expansion↓, wall thickness↑, LV end-diastolic volume preserved, myofibroblast number↑, collagen content↑ | [130] | |
| Gelin-S | Rat | LV EF↑, LV FS↑, neovascularization↑, collagen deposition↓ | [131] | |
| Methacrylic anhydride | Sheep | Regional wall thickness↑, infarcted area↓ (only for highly stiff scaffold) | [132] | |
| Methacrylic anhydride or/and hydroxyethylmethacrylate | Sheep | Wall thickness↑, vascularization↑, inflammation↑, LV end-systolic volume↓ (only for highly stiff, stable scaffold) | [133] | |
| Hyaluronic acid+gelatin | Human cardiosphere-derived cells | Mouse | Cardiac function↑, LV remodeling and abnormal heart morphology↓, viable tissue↑, wall thickness↑, cardiac and endothelial cellular differentiation, cellular engraftment↑, neovascularization↑, apoptosis↓ | [134] |
| Hyaluronic acid+silk fibroin | Rat bone marrow MSCs | Rat | LV inner diameter↓, wall thickness↑, FS↑, inflammation↓, apoptosis↓, vascularization↑, α-MHC expression↑, paracrine factor secretion↑ | [135] |
| Hyaluronic acid+chitosan+silk fibroin | – | Rat | LV inner diameter↓, wall thickness↑, LV FS↑, angiogenesis↑, paracrine factor expression↑ | [136] |
| Hyaluronic acid+butyric and retinoic acids | Human placenta-derived MSCs | Pig | Scar size↓, infarct core zone↓, angiogenesis↑, fibrosis↓, end-systolic wall thickening and circumferential shortening↑, high homology with healthy myocardium | [137] |
ATDSC adipose tissue-derived stem cell, bFGF basic fibroblast growth factor, BMMNC bone marrow mononuclear cell, CM cardiomyocyte, EC endothelial cell, EF ejection fraction, ESC embryonic stem cell, FS fractional shortening, HGF hepatocyte growth factor, IGF insulin growth factor, LV left ventricle/left ventricular, MHC myosin heavy chain, MI myocardial infarction, MSC mesenchymal stem cell, rTIMP recombinant tissue inhibitor of matrix metalloproteinases, SDF stromal cell-derived factor, VEGF vascular endothelial growth factor