Biodegradable magnesium implant enhances angiogenesis and alleviates medication-related osteonecrosis of the jaw in rats
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AbstractBackground
Medication-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.
Methods
MRONJ 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.
Results
Eight 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.
Conclusion
Biodegradable 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.
Medication-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.
Methods
MRONJ 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.
Results
Eight 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.
Conclusion
Biodegradable 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.
Acceptance Date12/03/2022
All Author(s) ListZhu W, Guo J, Yang W, Tao Z, Lan X, Wang L, Xu J, Qin L, Su Y
Journal nameJournal of Orthopaedic Translation
Year2022
Month3
Volume Number33
PublisherElsevier
Pages153 - 161
ISSN2214-031X
LanguagesEnglish-United States
KeywordsAngiogenesis, Biodegradable, implants
