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Biofunctional magnesium coated Ti6Al4V scaffold enhances osteogenesis and angiogenesis in vitro and in vivo for orthopedic application.

ABSTRACT: The insufficient osteogenesis and osseointegration of porous titanium based scaffold limit its further application. Early angiogenesis is important for scaffold survival. It is necessary to develop a multifunctional surface on titanium scaffold with both osteogenic and angiogenic properties. In this study, a biofunctional magnesium coating is deposited on porous Ti6Al4V scaffold. For osseointegration and osteogenesis analysis, in vitro studies reveal that magnesium-coated Ti6Al4V co-culture with MC3T3-E1 cells can improve cell proliferation, adhesion, extracellular matrix (ECM) mineralization and ALP activity compared with bare Ti6Al4V cocultivation. Additionally, MC3T3-E1 cells cultured with magnesium-coated Ti6Al4V show significantly higher osteogenesis-related genes expression. In vivo studies including fluorochrome labeling, micro-computerized tomography and histological examination of magnesium-coated Ti6Al4V scaffold reveal that new bone regeneration is significantly increased in rabbits after implantation. For angiogenesis studies, magnesium-coated Ti6Al4V improve HUVECs proliferation, adhesion, tube formation, wound-healing and Transwell abilities. HUVECs cultured with magnesium-coated Ti6Al4V display significantly higher angiogenesis-related genes (HIF-1? and VEGF) expression. Microangiography analysis reveal that magnesium-coated Ti6Al4V scaffold can significantly enhance the blood vessel formation. This study enlarges the application scope of magnesium and provides an optional choice to the conventional porous Ti6Al4V scaffold with enhanced osteogenesis and angiogenesis for further orthopedic applications.

SUBMITTER: Gao P

PROVIDER: S-EPMC7226632 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Biofunctional magnesium coated Ti6Al4V scaffold enhances osteogenesis and angiogenesis in vitro and in vivo for orthopedic application.

Gao Peng P Fan Bo B Yu Xiaoming X Liu Wenwen W Wu Jie J Shi Lei L Yang Di D Tan Lili L Wan Peng P Hao Yulin Y Li Shujun S Hou Wentao W Yang Ke K Li Xiaokang X Guo Zheng Z

Bioactive materials 20200512 3

The insufficient osteogenesis and osseointegration of porous titanium based scaffold limit its further application. Early angiogenesis is important for scaffold survival. It is necessary to develop a multifunctional surface on titanium scaffold with both osteogenic and angiogenic properties. In this study, a biofunctional magnesium coating is deposited on porous Ti6Al4V scaffold. For osseointegration and osteogenesis analysis, in vitro studies reveal that magnesium-coated Ti6Al4V co-cultu ...[more]

PMID: 32435721

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Project description:We have shown that the uniaxial cyclic tensile strain of magnitude 10% promotes and enhances osteogenesis of human mesenchymal stem cells (hMSC) and human adipose-derived stem cells (hASC) from normal, nonosteoporotic donors. In the present study, MSC from osteoporotic donors were analyzed for changes in mRNA expression in response to 10% uniaxial tensile strain to identify potential mechanisms underlying the use of this mechanical loading paradigm for prevention and treatment of osteoporosis. Human MSC isolated from three female, postmenopausal osteoporotic donors were analyzed for their responses to mechanical loading using microarray analysis of over 47,000 gene probes. Human MSC were seeded in three-dimensional collagen type I constructs to mimic the organic extracellular matrix of bone and 10% uniaxial cyclic tensile strain was applied to promote osteogenesis. Seventy-nine genes were shown to be regulated within hMSC from osteoporotic donors in response to 10% cyclic tensile strain. Upregulation of six genes were further confirmed with real-time RT-PCR: jun D proto-oncogene (JUND) and plasminogen activator, urokinase receptor (PLAUR), two genes identified as potential key molecules from network analysis; phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD) and wingless-type MMTV integration site family, member 5B (WNT5B), two genes with known importance in bone biology; and, PDZ and LIM domain 4 (PDLIM4) and vascular endothelial growth factor A (VEGFA), two genes that we have previously shown are significantly regulated in hASC in response to this mechanical stimulus. Function analysis indicated that 10% cyclic tensile strain induced expression of genes associated with cell movement, cell proliferation, and tissue development, including development in musculoskeletal and cardiovascular systems. Our results demonstrate that hMSC from aged, osteoporotic donors are capable of enhanced osteogenic differentiation in response to 10% cyclic tensile strain with significant increases in the expression of genes associated with enhanced cell proliferation, musculoskeletal development, and angiogenesis. Surprisingly, cyclic tensile strain of magnitude 10% not only enhanced osteogenesis in hMSC from osteoporotic donors, but also enhanced expression of angiogenic factors. Better understanding and methodologies to promote osteogenesis in hMSC from elderly, osteoporotic donors may greatly facilitate achieving long-term success in bone regeneration and functional bone tissue engineering for this ever-growing patient population.

Project description:BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis.MethodsMRONJ model was established and divided into the Veh + Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP + Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP + Mg group (BP-treated rat, with Mg implant), BP + Mg + SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP + Mg + BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP + Mg + SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis.ResultsEight weeks after surgery, the BP + Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP + Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP + Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased.ConclusionBiodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ.The translational potential of this articleThis work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ.

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Biofunctional magnesium coated Ti6Al4V scaffold enhances osteogenesis and angiogenesis in vitro and in vivo for orthopedic application.

Publications

Biofunctional magnesium coated Ti6Al4V scaffold enhances osteogenesis and angiogenesis <i>in vitro</i> and <i>in vivo</i> for orthopedic application.

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