Table 3 In vivo improvements achieved with scaffolds composed of the polysaccharides chitosan, alginate or hyaluronic acid

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]