Cellular mechanisms of biodegradable zinc and magnesium materials on promoting angiogenesis
Source abstract
Abstract
Biodegradable metals, zinc and magnesium, have been regarded as next-generation, biomedical implant materials to promote tissue repair and regeneration. These implants might also promote the vascularization of surrounding neotissue. Released metallic ions, Zn2+ and Mg2+, show promise in vitro to implement vessel growth by stimulating the expression of pro-angiogenic cytokines, yet there is little known regarding how cellular responses transcend to influence the tissue environment. This study serves to optimize angiogenic behavior using EA.hy926 endothelial cultures exposed to Zn2+ and Mg2+ gradients and observe the translation of these effects on blood vessel development via the in ovo chorioallantoic membrane (CAM) assay. Findings indicate that Zn2+ 10 μM and Mg2+ 10 mM instigate the most prominent effects using endothelial cultures via scratch wound and tube formation assays, yet higher concentrations at Zn2+ 50 μM and Mg2+ 50 mM encourage significant angiogenesis along the CAM. Immunoblotting results also conclude the presence and upregulation of cytokines involved in vessel growth. Optimizing the angiogenic potential of Zn2+ and Mg2+ separately sheds light to design future engineering constructs for promoting blood vessel development and successful assimilation between host and implant tissue.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Magnesium Alloys: Properties and Applications · Bone Tissue Engineering Materials · Tissue Engineering and Regenerative Medicine
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (78)
Show source-provided references
1. Engineering vascularized tissue10.1038/nbt0705-821 ↗
2. Angiogenesis and wound repair: when enough is enough10.1189/jlb.4MR0316-102R ↗
3. A short discourse on vascular tissue engineering10.1038/s41536-017-0011-6 ↗
4. Vascularization of engineered tissues: approaches to promote angiogenesis in biomaterials10.2174/156802608783790983 ↗
5. Generation of cerebral organoids from human pluripotent stem cells10.1038/nprot.2014.158 ↗
6. Bioactive electrospun scaffolds for wound healing applications: a comprehensive review10.1016/j.polymertesting.2020.106952 ↗
7. Investigation of angiogenesis and its mechanism using zinc oxide nanoparticle-loaded electrospun tissue engineering scaffolds10.1039/C4RA07361D ↗
8. How smart do biomaterials need to be? A translational science and clinical point of view10.1016/j.addr.2012.07.009 ↗
9. Zinc-based biomaterials for regeneration and therapy10.1016/j.tibtech.2018.10.009 ↗
10. The prospects of zinc as a structural material for biodegradable implants—a review paper10.3390/met7100402 ↗
11. Biodegradable magnesium alloys developed as bone repair materials: a review10.1155/2018/9216314 ↗
12. Byrd-Bredbenner · 2009
13. Three classes of C2H2 zinc finger proteins10.1007/PL00000885 ↗
14. Zinc regulates vascular endothelial cell activity through zinc-sensing receptor ZnR/GPR39
15. GPR39: a zn 2+-activated G protein-coupled receptor that regulates pancreatic, gastrointestinal and neuronal functions10.1007/s00018-010-0517-1 ↗
16. Magnesium and microvascular endothelial cells: a role in inflammation and angiogenesis10.2741/1610 ↗
17. Endothelial cellular responses to biodegradable metal zinc10.1021/acsbiomaterials.5b00319 ↗
18. Magnesium deficiency and increased inflammation: current perspectives10.2147/JIR.S136742 ↗
19. High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro10.1016/j.bbadis.2004.02.004 ↗
20. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs10.1538/expanim.14-0059 ↗
21. The chicken chorioallantoic membrane model in biology, medicine and bioengineering10.1007/s10456-014-9440-7 ↗
22. The chick chorioallantoic membrane as an in vivo xenograft model for burkitt lymphoma10.1186/1471-2407-14-339 ↗
23. The chorioallantoic membrane assay for biomaterial testing in tissue engineering: a short-term in vivo preclinical model10.1089/ten.tec.2017.0186 ↗
24. The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model10.1016/j.mod.2016.05.003 ↗
25. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering10.1038/srep32168 ↗
26. The use of the chick embryo CAM assay in the study of angiogenic activiy of biomaterials10.1016/j.mvr.2020.104026 ↗
27. Trace metal levels in commercially prepared tissue culture media10.1016/0040-8166(80)90016-6 ↗
28. Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle10.7554/eLife.51107 ↗
29. Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells10.1007/s12263-011-0248-4 ↗
30. Cellular magnesium homeostasis10.1016/j.abb.2011.05.010 ↗
31. Endothelial responses of magnesium and other alloying elements in magnesium-based stent materials10.1039/C4MT00244J ↗
32. Biphasic responses of human vascular smooth muscle cells to magnesium ion10.1002/jbm.a.35570 ↗
33. Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA. Hy 926 cells10.1016/j.lfs.2005.10.016 ↗
34. The in ovo chick chorioallantoic membrane (CAM) assay as an efficient xenograft model of hepatocellular carcinoma
35. Exosomes derived from AKt-modified human umbilical cord mesenchymal stem cells improve cardiac regeneration and promote angiogenesis via activating platelet-derived growth factor D10.5966/sctm.2016-0038 ↗
36. Age-dependent accumulation of dicarbonyls and advanced glycation endproducts (AGEs) associates with mitochondrial stress10.1016/j.freeradbiomed.2020.12.021 ↗
37. High dietary advanced glycation end products impair mitochondrial and cognitive function10.3233/JAD-191236 ↗
38. Development of an intact intervertebral disc organ culture system in which degeneration can be induced as a prelude to studying repair potential10.1007/s00586-011-1721-x ↗
39. Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells
40. Detection of necrosis by release of lactate dehydrogenase activity
41. Copper ions interfere with the reduction of the water-soluble tetrazolium salt-810.1021/tx400414c ↗
42. Limitation of water-soluble tetrazolium salt for the cytocompatibility evaluation of zinc-based metals10.3390/ma14216247 ↗
43. Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis
44. Vascular endothelial growth factor–stimulated actin reorganization and migration of endothelial cells is regulated via the serine/threonine kinase akt10.1161/01.RES.86.8.892 ↗
45. Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling10.1172/JCI1699 ↗
46. Magnesium deficiency causes loss of response to intermittent hypoxia in paraganglion cells10.1074/jbc.M109.004424 ↗
47. Three-dimensional printed mg-doped β-TCP bone tissue engineering scaffolds: effects of magnesium ion concentration on osteogenesis and angiogenesis in vitro10.1007/s13770-019-00192-0 ↗
48. Improving the osteogenic and angiogenic properties of synthetic hydroxyapatite by dual doping of bivalent cobalt and magnesium ion10.1016/j.ceramint.2015.05.090 ↗
49. The zinc-sensing receptor GPR39 in physiology and as a pharmacological target10.3390/ijms22083872 ↗
50. The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis10.5604/17322693.1009705 ↗
51. Mechanosensitive systems at the cadherin–F-actin interface10.1242/jcs.109447 ↗
52. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis10.1016/j.bbamem.2007.09.003 ↗
53. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization10.1161/01.RES.0000191547.64391.e3 ↗
54. Functional role of inorganic trace elements in angiogenesis—Part II: cr, si, zn, cu, and S10.1016/j.critrevonc.2015.05.011 ↗
55. The role of inflammatory cytokines in endothelial dysfunction10.1007/s00395-008-0733-0 ↗
56. The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art10.1007/s10456-009-9146-4 ↗
57. Endothelial cell tube formation assay for the in vitro study of angiogenesis
58. Role of aminopeptidase in angiogenesis10.1248/bpb.27.772 ↗
59. Matrix metalloproteinases: fold and function of their catalytic domains. Biochimica et biophysica acta (BBA)-molecular
60. Using ex Ovo chick chorioallantoic membrane (CAM) assay to evaluate the biocompatibility and angiogenic response to biomaterials10.1021/acsbiomaterials.9b00172 ↗
61. Chorioallantoic membrane assay as model for angiogenesis in tissue engineering: focus on stem cells10.1089/ten.teb.2020.0048 ↗
62. Evolving applications of the egg: chorioallantoic membrane assay and ex vivo organotypic culture of materials for bone tissue engineering10.1177/2041731420942734 ↗
63. Douglas-Byrd · 2013
64. The in ovo CAM-assay as a xenograft model for sarcoma
65. The antiangiogenic effects of levosimendan in a CAM assay10.1016/j.mvr.2012.01.002 ↗
66. Importance of albumen during embryonic development in avian species, with emphasis on domestic chicken10.1017/S0043933914000567 ↗
67. A review of in-vivo and in-vitro real-time corrosion monitoring systems of biodegradable metal implants10.3390/app10093141 ↗
68. A pure zinc membrane with degradability and osteogenesis promotion for guided bone regeneration: in vitro and in vivo studies10.1016/j.actbio.2020.02.024 ↗
69. Stimulation of in vitro and in vivo osteogenesis by ti-mg alloys with the sustained-release function of magnesium ions10.1016/j.colsurfb.2020.111360 ↗
70. Multifunctions of dual Zn/Mg ion co-implanted titanium on osteogenesis, angiogenesis and bacteria inhibition for dental implants10.1016/j.actbio.2016.11.067 ↗
71. Acceleration of bone formation and adhesion ability on dental implant surface via plasma electrolytic oxidation in a solution containing bone ions10.3390/met11010106 ↗
72. In vivo and in vitro evaluation of a biodegradable magnesium vascular stent designed by shape optimization strategy10.1016/j.biomaterials.2019.119414 ↗
73. A promising biodegradable magnesium alloy suitable for clinical vascular stent application10.1038/srep46343 ↗
74. Comparative assessment of in vitro and in vivo biodegradation of mg-1Ca magnesium alloys for orthopedic applications10.3390/ma14010084 ↗
75. Biofunctional magnesium coated Ti6Al4V scaffold enhances osteogenesis and angiogenesis in vitro and in vivo for orthopedic application
76. Analysis of time-series gene expression data to explore mechanisms of chemical-induced hepatic steatosis toxicity10.3389/fgene.2018.00396 ↗
77. Molecular mediators of angiogenesis10.1097/BCR.0b013e3181c7ed82 ↗
78. Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo10.1371/journal.pone.0015048 ↗