Table 1.
Significant hydrogel properties for vasculature.
| Hydrogel composition | Cell sources | Shaping mechanism | Advantages of shaping mechanism for vascularization | Significant hydrogel properties | Advantages for vasculature | Refs. |
|---|---|---|---|---|---|---|
| GelMA, gelatin | HUVECs | Thermal crosslinking and photocrosslinking | Smooth gel filament extrusion at sol-gel transition and rapid UV gelation for structural support | Natural sol-gel transition of the hydrogel systems; biocompatibility; porous structure | Formation of the interconnected tubular channels within well-defined 3D architectures; a confluent endothelial layer in the inner surface of the channels; in situ endothelialization of the channels | [75] |
| Alginate, gelatin | HUVECs | Ionic crosslinking and genepin penetration | Rapidly fixation of microrods architectures and inducing HUVECs migration | Rapidly crosslinking of alginate and controllable fixation of gelatin | Unique fabrication of HUVECs-laden microrods and regulation of HUVECs migration within hydrogel microrods; formation of new capillaries and organization of intensive vascular networks in mice after injection for 21 d | [78] |
| GelMA, HGSM | mBMSCs | Photocrosslinking and covalently crosslinking | Enhanced mechanical properties showing self-healing capability | Synthetization of host-guest supramolecular hydrogel (HGGelMA) with high compressive strength and an excellent stretching ability; about 400% water content; 5.25-fold compression modulus of the HGGelMA (0.63 MPa) than that of pure GelMA (0.11 MPa) | Higher expression level of blood vessel-related genes (SMA, CD31, and PDGF) in vivo than that of pure GelMA | [87] |
| GelMA, PEO | HUVECs, HepG2, and NIH/3T3 cells | Photocrosslinking and leaching | The hierarchical porous structures enhancing proliferation of HUVECs | Increased Yong's modulus of the GelMA-PEO with the increase of PEO concentration | 3- and 4-fold proliferation of HUVECs in the hierarchical porous GelMA than that of standard GelMA on 3 d and 7 d, respectively | [86] |
| GelMA, gelatin | HUVECs | Thermal crosslinking and photocrosslinking | Fabrication of pure-gelatin-based hollow structures for HUVECs encapsulation | Controllable gel point and pores diameters by adjusting gelatin and GelMA concentration, respectively | Long-term maintenance of hollow structures in culture medium | [50] |
| GelMA, NAGA, nanoclay | HUVECs | Photocrosslinking | Generation of a scalable large-length vascular-like microtube with variable outer and inner diameter | Marvelous mechanical properties with Young's modulus (≈21 MPa), a stretchability (≈500%), a tensile strength (≈22 MPa), an anti-fatigue performance (≈200 cycles), and a burst pressure (≈2500 mmHg) | Good permeability; formation of a complete single endothelial layer using HUVECs; the positive expression of various angiogenesis-related factors | [89] |
| GelMA, gelatin, HA | HUVECs, SMCs | Photocrosslinking | Spatial distribution of HUVECs and SMCs mimicking native vasculature | Adjustable tensile stress, Yong's modulus, and pore sizes | Development of heterogeneous bilayer tubular structures with HUVECs and SMCs laden on the luminal and outer surfaces, respectively | [92] |
| GelMA, alginate | HUVECs, DFs, and hKCs | Ionic crosslinking and photocrosslinking | Recapitulating native skin architectures by distributing HUVECs, DFBs, and KCs into three main layers | Increased compressive modulus and viscosity with an increase of alginate concentration | Higher secretion of Pro-Collα1 and lower levels of MMP-1 at 7.5% (w/v) GelMA concentration | [91] |
| Alginate, collagen | Keratinocyte, FBs | Cryogenic process (−30 °C) | Rapidly generation of vascular-like structures with core and shell at low temperature | Good structural stability; 7 times Young's modulus of the alginate/collagen scaffold than that of pure collagen, similar pore-structure, and cell viability | A hybrid scaffold with alginate core and collagen shell; the formation of granulation tissues and vascularization in vivo for 14 d | [100] |
| ELP | MSCs, HUVECs | Photocrosslinking | Adjustable crosslinking density mimicking stretchability of vasculature | Four times length after stretching; increased ELP concentration resulting in the increase in the crosslinking density | Maintenance of cell viabilities up to 7 d; limited cell spreading due to the lack of RGD peptide; no lymphocyte infiltration in vivo | [102] |
| PEGDA, GIA-PEGDA, RGD-PEGMA | HUVECs | Photocrosslinking | Biocompatible UV irradiation to HUVECs facilitating cell attachment | Enzymatic degradation of GIA modified PEG hydrogels; decrease in crosslinking density due to degradation | Initial HUVECs attachment at 4 h; elongation and reorganization of cells at 12 h; formation of capillary-like networks at 24 h | [80] |
| GelMA, PEG, SPELA | hMSCs, ECFCs | Photocrosslinking | Controllable release of angiogenic GFs using various UV curing polymers | Spatiotemporal release of BMP2 and VEGF using GF-grafted nanogel; the release kinetics of GFs depending on the PEG MW and lactide/glycolide ratio | Construction of osteogenic SPELA gel containing vasculogenic GelMA microchannels; increased vasculogenic and osteogenic differentiation of ECFCs and hMSCs | [135] |
| GelMA, alginate, PEGOA | hSMCs, HUCs, HUVECs | Ionic crosslinking and photocrosslinking | Direct extrusion of perfusable circumferentially multilayered tissues due to rapid ionic crosslinking | Significant increased mechanical strength compared with one or two-component hydrogels; alternative shapes and sizes without changing device | The spatial distribution of hSMCs and HUCs; creation of blood vessel tissue using hSMCs and HUVECs | [82] |
| GelMA | ECFCs, MSCs | Photocrosslinking | Adjustable physical properties at various UV exposure time for optimization of vascular luminal formation | Decreased degradation, increased elastic modulus, and viscous modulus with the increase of UV exposure time | Formation of ECGC-lined microvessels in vivo for 7 d after implantation, excessive GelMA crosslinking hindered luminal structures formation in vivo | [158] |
Abbreviations: CD31 - platelet endothelial cell adhesion molecule-1, DFS - dermal fibroblasts, ECFCs - human endothelial colony-forming cells, ELP - elastin-like polypeptides, GelMA - gelatin methacrylate, GIA - collagen type I-derived peptide, HepG2 - human hepatocellular carcinoma cells, HGGelMA - host-guest supramolecular GelMA hydrogel, HGSM - host-guest supramolecule, hKCs - human keratinocytes, hNDFs - human neonatal dermal fibroblasts, hSMCs - human bladder smooth muscle cells, HUCs - human urothelial cells, HUVECs - human umbilical vein endothelial cells, mBMSCs - mouse marrow mesenchymal stem cells, NAGA - N-acryloyl glycinamide, NIH/3T3 - mouse embryonic fibroblasts, PEGDA - poly(ethylene glycol) diacrylate, PDGF - platelet derived growth factor, PEG - poly(ethylene glycol), PEGOA - eight-arm poly(ethylene glycol) acrylate, PEO - poly(ethylene oxide), RGD - arginine-glycine-aspartate, SF - silk fibroin, SMA - smooth muscle actin, SPELA - lactide-chain-extended star polyethylene glycol.