Review Article

Bioprinting of Vascularized Tissue Scaffolds: Influence of Biopolymer, Cells, Growth Factors, and Gene Delivery

Table 1

Influence of biological factor on tissue vascularization.

Biological factorPercentage/dosing amountScaffold detailsFabrication methodIn vitro/in vivoResults/findingsReference

PLLA enriched with basement membrane proteins (Matrigel)5% PLLA6 × 6 × 1 mmSolvent-casting particulate leachingIn vivoCreation of uniform, branched microvascular network[91]
Silk fibroin micronets5 × 5 mm3D nonwoven substrates made by boiling cocoons and soaking in 98% formic acidIn vivoPromising vascularization by preculturing with osteoblasts[157]
Gelatin-based sacrificial filament was embedded into a collagen scaffold10% gelatin and 3.0 mg/mL collagenChannels in the range of 0.7–1.5 mm for the width and 0.5–1.2 mm for the height3D bioprintingIn vitro (human umbilical vein endothelial cells)Supporting the viability of tissue up to 5 mm in distance at 5 million cells/mL density under the physiological flow condition[1, 158]
Human outgrowth endothelial cells (OECs)Starch-poly(caprolactone)As described in [159]In vivoOsteoblasts played a pericyte‐like role and supported OEC-derived vessels[159]
Fibroblast growth factor-loaded microspheresAlginate scaffold (2% (w/v)) that incorporates tiny poly(lactic-co-glycolic acid) microspheresHigh porosity (90%) with an average pore size of 130 micronsAs described in [160]In vitro basic fibroblast growth factor (bFGF)The released bFGF induced the formation of large and matured blood vessels[161]
Vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1)Alginate-sulfate/alginate (1% (w/v) solution of sodium alginate and a 0.3% (w/v) solution of hemicalcium gluconate for alginate crosslinking)Diameter of 11 mm and thickness of 3 mmFreeze-dry techniqueIn vivoCreation of mature vessels after 3 months[124]
VEGF and Ang-1Hyaluronan (HA)As described in [159]In vivoCreation of higher microvessel density after 14 days[116]
FGF-4 plasmidGelatin hydrogelInjection of GHG-DNA complex into the hindlimb muscleIn vivoPromotion of angiogenesis in the newly developed tissues in the GHG-FGF4 group than the naked FGF4-gene four weeks after gene transfer[147]
Plasmid encoding PDGFSubcutaneously implanted PLG spongesGas foaming/particulate-leaching processIn vivo/in vitroImprovement of ECM deposition and capillary formation[148]
Plasmid-mediated VEGFPLGA nanoparticlesInjection of the suspension of VEGF-loaded nanoparticles (VEGF-NPs) into myocardial tissuesIn vivoHigher capillary number compared to the naked plasmid DNA group[149]