Department of Biomedical Engineering, Ankara University, Ankara 06830, Turkey.
Anatomic Pathology Department, National Veterinary School of Toulouse, Toulouse 31300, France.
ACS Biomater Sci Eng. 2024 Jul 8;10(7):4452-4462. doi: 10.1021/acsbiomaterials.4c00358. Epub 2024 Jun 14.
Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.
镁基可生物降解金属植入物在骨科和牙科领域的应用越来越受到关注。然而，它们目前的应用受到其高腐蚀率、降解速度以及离子和气泡快速释放到生理介质中的限制。本研究旨在研究涂层镁基植入物在绵羊颅骨缺损模型中的成骨和血管生成潜力。尽管已经在一定程度上研究了它们的成骨潜力，但它们在促进血管化骨形成方面的潜力尚未详细研究。我们研究了用锌（Zn）或镓（Ga）掺杂的磷酸钙（CaP）涂层改性的镁钙（MgCa）基合金作为控制其降解速度同时增强骨再生能力的策略的潜力。将 MgCa 及其带有 CaP 涂层的植入物（MgCa/CaP）作为未掺杂或掺杂 Zn 或 Ga（分别为 MgCa/CaP + Zn 和 MgCa/CaP + Ga）植入绵羊颅骨中创建的骨缺损中。MgCa 植入物在术后 4 周时比其他植入物降解更快，重量损失约为 50%，而 MgCa/CaP 为 15%，在存在 Zn 和 Ga 与 CaP 涂层时小于 10%。对植入物表面的扫描电子显微镜（SEM）分析也表明，MgCa 植入物的结构破坏程度最大。放射学评估显示，对 MgCa 植入物进行 CaP 表面改性可诱导缺陷内更好的骨再生以及增强骨-植入物表面整合。在微 CT 评估中，MgCa/CaP + Ga 情况下缺陷内的骨体积（%）约为 25%，而未掺杂 MgCa 组约为 15%。在 H&E 和 Masson 三色染色切片的组织病理学检查中，还观察到 MgCa/CaP + Ga 植入物的骨再生增加了>1.5 倍。骨再生（抗骨桥蛋白）和血管生成（抗 CD31）在缺陷部位的免疫组织化学分析表明，在 Ga 和 Zn 掺杂的 CaP 涂层植入物中，标记物的表达增加了>2 倍。Zn 掺杂的植入物进一步表现出低炎症反应、明显的骨再生和所有植入物组中的新血管生成。这些发现表明，Ga 和 Zn 掺杂的 CaP 涂层是控制降解速度以及实现基于镁的合金植入物增强骨再生能力的重要策略。
