Bioprinting of pre-vascularized constructs for enhanced in vivo neo-vascularization
Source abstract
Abstract
Abstract Pre-vascularization has been receiving significant attention for developing implantable engineered 3D tissues. While various pre-vascularization techniques have been developed to improve graft vascularization, the effect of pre-vascularized patterns on in vivo neo-vessel formation has not been studied. In this study, we developed a functional pre-vascularized construct that significantly promotes graft vascularization and conducted in vivo evaluations of the micro-vascular patterns (μVPs) in various printed designs. μVP formation, composed of high-density capillaries, was induced by the co-printing of endothelial cells and adipose-derived stem cells (ADSC). We implanted the printed constructs with various μVP designs into a murine femoral arteriovenous bundle model and evaluated graft vascularization via 3D visualization and immune-histological analysis of the neo-vessels. The μVP-distal group (μVP located away from the host vessel) showed approximately two-fold improved neo-vascularization compared to the μVP-proximal group (μVP located near the host vessel). Additionally, we confirmed that the μVP-distal group can generate the angiogenic factor gradient spatial environment for graft vascularization via computational simulations. Based on these results, the ADSC mono pattern (AMP), which secretes four times higher angiogenic factors than μVP, was added to the μVP + AMP group design. The μVP + AMP group showed approximately 1.5- and 1.9-fold higher total sprouted neo-vessel volume than the μVP only and AMP only groups, respectively. In immunohistochemical staining analysis, the μVP + AMP group showed two-fold improved density and diameter of the matured neo-vessels. To summarize, these findings demonstrate graft vascularization accelerated due to design optimization of our pre-vascularized constructs. We believe that the developed pre-vascularization printing technique will facilitate new possibilities for the upscaling of implantable engineered tissues/organs.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: 3D Printing in Biomedical Research · Electrospun Nanofibers in Biomedical Applications · Tissue Engineering and Regenerative Medicine
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (45)
Show source-provided references
1. Regenerative medicine: current therapies and future directions10.1073/pnas.1508520112 ↗
2. A decade of progress in tissue engineering10.1038/nprot.2016.123 ↗
3. Vascular tissue engineering: progress, challenges, and clinical promise10.1016/j.stem.2018.02.009 ↗
4. Multivascular networks and functional intravascular topologies within biocompatible hydrogels10.1126/science.aav9750 ↗
5. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels10.1126/sciadv.aaw2459 ↗
6. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis10.1038/nmat4570 ↗
7. In vivo anastomosis and perfusion of a three-dimensionally-printed construct containing microchannel networks10.1089/ten.tec.2015.0239 ↗
8. 3D liver tissue model with branched vascular networks by multimaterial bioprinting10.1002/adhm.202101405 ↗
9. 3D bioprinting of engineered tissue flaps with hierarchical vessel networks (vesselnet) for direct host‐to‐implant perfusion10.1002/adma.202102661 ↗
10. Engineering blood vessels and vascularized tissues: technology trends and potential clinical applications10.1042/CS20180155 ↗
11. Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature10.1089/ten.tea.2008.0314 ↗
12. An engineered muscle flap for reconstruction of large soft tissue defects10.1073/pnas.1402679111 ↗
13. Geometric control of vascular networks to enhance engineered tissue integration and function10.1073/pnas.1217796110 ↗
14. High-resolution acoustophoretic 3D cell patterning to construct functional collateral cylindroids for ischemia therapy10.1038/s41467-018-07823-5 ↗
15. A novel strategy to engineer pre-vascularized 3-dimensional skin substitutes to achieve efficient, functional engraftment10.1038/s41598-019-44113-6 ↗
16. Flexible adipose‐vascular tissue assembly using combinational 3D printing for volume‐stable soft tissue reconstruction10.1002/adhm.202001693 ↗
17. 3D microphysiological system‐inspired scalable vascularized tissue constructs for regenerative medicine10.1002/adfm.202105475 ↗
18. Engineering transferrable microvascular meshes for subcutaneous islet transplantation10.1038/s41467-019-12373-5 ↗
19. In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease10.1126/scitranslmed.aah5505 ↗
20. Engineering tissue‐specific, multiscale microvasculature with a capillary network for prevascularized tissue10.1002/smtd.202100632 ↗
21. The vascularised chamber as an in vivo bioreactor10.1016/j.tibtech.2018.05.009 ↗
22. Molecular mechanisms and clinical applications of angiogenesis10.1038/nature10144 ↗
23. The effect of matrix density on the regulation of 3D capillary morphogenesis10.1529/biophysj.107.120774 ↗
24. Engineering vascularized flaps using adipose‐derived microvascular endothelial cells and mesenchymal stem cells10.1002/term.2436 ↗
25. Assessing the permeability of engineered capillary networks in a 3D culture10.1371/journal.pone.0022086 ↗
26. Engineering a chemically defined hydrogel bioink for direct bioprinting of microvasculature10.1021/acs.biomac.0c00947 ↗
27. ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation10.1083/jcb.201404140 ↗
28. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis10.1016/S0092-8674(00)81010-7 ↗
29. Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis10.1182/blood-2011-02-338426 ↗
30. Molecular regulation of angiogenesis and lymphangiogenesis10.1038/nrm2183 ↗
31. “Living” microvascular stamp for patterning of functional neovessels; orchestrated control of matrix property and geometry10.1002/adma.201103207 ↗
32. 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments10.1002/adma.201806899 ↗
33. Angiogenic effects and crosstalk of adipose-derived mesenchymal stem/stromal cells and their extracellular vesicles with endothelial cells10.3390/ijms221910890 ↗
34. Bone tissue engineering using adipose‐derived stem cells and endothelial cells: effects of the cell ratio10.1111/jcmm.15374 ↗
35. 3D printed HUVECs/MSCs cocultures impact cellular interactions and angiogenesis depending on cell-cell distance10.1016/j.biomaterials.2019.119423 ↗
36. Mature vessel networks in engineered tissue promote graft–host anastomosis and prevent graft thrombosis10.1073/pnas.1814238116 ↗
37. Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs10.1016/j.biomaterials.2020.120594 ↗
38. Pre-vascularized dermis model for fast and functional anastomosis with host vasculature10.1016/j.biomaterials.2018.11.018 ↗
39. Cell-assembled extracellular matrix (CAM): a human biopaper for the biofabrication of pre-vascularized tissues able to connect to the host circulation in vivo10.1088/1758-5090/ac2f81 ↗
40. Consensus guidelines for the use and interpretation of angiogenesis assays10.1007/s10456-018-9613-x ↗
41. Mouse models to study angiogenesis, vasculogenesis and arteriogenesis in the context of cardiovascular diseases10.2741/3454 ↗
42. Microchannel network hydrogel induced ischemic blood perfusion connection10.1038/s41467-019-13993-7 ↗
43. Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction10.1016/j.biomaterials.2016.04.031 ↗
44. 3D-printed vascular networks direct therapeutic angiogenesis in ischaemia10.1038/s41551-017-0083 ↗
45. Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts10.1038/s41467-019-08388-7 ↗