Table 3.
Construction of various organs with specific vascular morphology by hydrogel and its application in tissue regeneration.
| Hydrogel types | Cell sources | Organoid types | Vascular morphology/signals | Significant advantages of hydrogels | Major results | Ref. |
|---|---|---|---|---|---|---|
| GelMA, HAMA | HIF-1α mutated MDSCs | Corpus cavernosa | Ingrowth of vascularized tissue ingrowth and promotion of neovascularization | Similar multi-scale porous structure and Yong's modulus of hydrogel scaffolds to native corpus cavernosum | Heparin coating and secretion of VEGF, PDGF, and SDF-1 from MDSCs; restoration of the erectile and ejaculation function | [136] |
| GelMA | HDFs, HUVECs | Skin flap | Formation of HUVEC- tubes; increased density of microvessels in vivo | Controllable mechanical and degradation properties | Supporting for HUVECs proliferation and migration; a rapid formation of HUVEC-tubes | [157] |
| GelMA, gelatin | BMSCs | Spinal cord | Increased number of vascular ECs in vivo quantified by CD31 and synaptophysin staining | High elasticity and water content of the hydrogel scaffold | promotion of differentiation of BMSCs into neurons; formation of glial scar | [130] |
| GelMA, MBGNs | MC3T3-E1 | Periosteum | Formation of the initial circular lumen and further regular annular lumen by ECs after surgery for 4 and 8 weeks, respectively | Prolonged ion release, better mechanical strength, and more durable degradation time compared to pure GelMA | Fabrication of GelMA/MBGNs by physically mixture and GelMA-G-MBGNs by chemically modification, separately; quantified neovascularization GelMA-GMBGNs group > GelMA/MBGNs group > GelMA group > blank group at the same time after implantation | [107] |
| GelMA | BMSCs | Endochondral bone | GelMA architectures with interconnected microchannels in a diameter ranging from 265 to 1225 μm | Easy manipulating hydrogel architectures with hollow microchannels | Intensive vascular networks; enhanced vascularization within core regions of the microchannel GelMA templates; promotion of osteoclast/immune cell invasive and vascularization upon implantation | [95] |
| HAMA, GelMA | HUVECs, ADMSCs | Bone | Complex capillary-like networks in vitro; increased vessel density and area distribution of microvessels in vivo | Bioactive hybrid hydrogel solutions for differentiation of stem cells | Co-culture of HUVECs and ADMSCs within hydrogel coating improved vascularization in vitro, along with no significant effects on osteogenesis; functional anastomosis of capillaries in scaffold with the host vasculature | [163] |
| GelMA | HUVECs, hMSCs | Bone | 500 μm hollow channels within hard PLA scaffold; formation of capillary-like and lumen-like structures within biphasic constructs | Formation of biphasic constructs using hydrogel and delivery of angiogenic GFs within hydrogel matrixes | The formation of rounded morphologies of encapsulated cells within GelMA; enhanced osteogenic differentiation and vascularization due to the presence of BMP-2 peptide and VEGF peptide | [165] |
| Alginate, ceramic ink | HUVECs | Bone | Existing of about 500 μm hollow pipe in the middle of the strut | The regulation of HUVECs migration by ionic products in vitro | Promotion of bone marrow formation and bone marrow cavity reconnection | [96] |
| Alginate, gelatin | BMSCs | Bone | The positive expression of CD31 after injection for 3 weeks | Increased pore size with the increase of Mg particles within hydrogel | Development of in situ pore-forming injectable hydrogels | [85] |
Abbreviations: ADMSCs - adipose-derived mesenchymal stem cells, BMP-2 - bone morphogenetic protein-2, BMSCs - bone marrow mesenchymal stem cells, CD31 - platelet endothelial cell adhesion molecule-1, GelMA - gelatin methacrylate, GFs - growth factors, HAMA - methacrylate hyaluronic acid, HDFs - human dermal fibroblasts, hMSCs - human marrow mesenchymal stem cells, HUVECs - human umbilical vein endothelial cells, MC3T3-E1 - mouse embryonic osteoblasts precursor cells, MDSCs - muscle-derived stem cells, PDGF - platelet derived growth factor, VEGF- vascular endothelial growth factors.