Parau Anca C, Büyüksungur Senem, Li Guanhao, Liu Quan, Badillo Ernesto, Blum Laura, Schmidt Jürgen, Pana Iulian, Vitelaru Catalin, Marinescu Ioana M, Dinu Mihaela, Smuglov Michael, Schmuttermaier Christina, Tanir Tugba E, Klüter Harald, Hasirci Nesrin, Kzhyshkowska Julia, Dragomir Alina Vladescu
National Institute of Research and Development for Optoelectronics - INOE 2000, 409 Atomistilor St. 077125 Magurele, Romania.
Middle East Technical University (METU), BIOMATEN - Biomaterials and Tissue Engineering Center of Excellence, Ankara 06800, Turkey.
J Adv Res. 2025 Jan 27. doi: 10.1016/j.jare.2025.01.045.
Chronic inflammation leading to implant failure present major challenges in orthopedics, dentistry, and reconstructive surgery. Titanium alloys, while widely used, often provoke inflammatory complications. Zinc (Zn)-doped calcium phosphate (CaP) coatings offer potential to enhance implant integration by improving corrosion resistance, bioactivity, and immunocompatibility.
The objective of the study was to develope novel coating composition based on zinc-doped CaP coatings on Ti64 alloy implants that for the first time combines improved corrosion resistance, antibacterial properties and principally improved compatibility with the innate immunity primarily due to the proper programming of resident tissue macrophages to promote long-term implant acceptance.
Ti64 substrates were coated with CaP and Zn-doped CaP using the microarc oxidation (MAO) technique. The adhesion between substrate and coatings are investigated by the progressive scratch test. The corrosion resistance and bioactivity were evaluated through electrochemical tests and simulated body fluid immersion. RNA sequencing was used to assess inflammatory responses in human primary macrophages. Antibacterial efficacy was tested against Escherichia coli and Staphylococcus aureus.
Zn addition significantly increased the adhesion of the coatings to Ti64 alloy, doubling up the critical load (from 4 N to 11 N). Zn-doped CaP coatings demonstrated enhanced corrosion resistance and increased biomineralization. RNA sequencing revealed that Zn addition suppressed inflammatory and promoted tolerogenic macrophage programming. Most pronounced effects was compensatory effect Zn on the CaP-supressed oxidative phosphorylation and lysosomal pathways in healing macrophages, and by upregulation of metallothioneins. Zn-doped coatings also exhibited superior antibacterial efficacy, reducing E. coli and S. aureus colonization by 99 % and 90 %, respectively.
Zn-doped CaP coatings on Ti64 implants significantly improved corrosion resistance, bioactivity, and antibacterial performance. We developed an advanced multifunctional biomaterial equipped with beneficial anti-inflammatory and tissue integrative programming of innate immunity providing principal advantages for the long-term implant integration and reducing the implant failure risks.
导致植入物失败的慢性炎症给骨科、牙科和重建外科带来了重大挑战。钛合金虽然被广泛使用，但常常引发炎症并发症。掺杂锌（Zn）的磷酸钙（CaP）涂层通过提高耐腐蚀性、生物活性和免疫相容性，为增强植入物整合提供了潜力。
本研究的目的是在Ti64合金植入物上开发基于掺杂锌的CaP涂层的新型涂层组合物，该涂层首次结合了改进的耐腐蚀性、抗菌性能，并且主要由于对驻留组织巨噬细胞进行适当编程以促进长期植入物接受，从而显著提高了与先天免疫的相容性。
使用微弧氧化（MAO）技术在Ti64基底上涂覆CaP和掺杂锌的CaP涂层。通过渐进划痕试验研究基底与涂层之间的附着力。通过电化学测试和模拟体液浸泡评估耐腐蚀性和生物活性。使用RNA测序评估人原代巨噬细胞中的炎症反应。测试了对大肠杆菌和金黄色葡萄球菌的抗菌效果。
添加锌显著增加了涂层与Ti64合金的附着力，使临界载荷加倍（从4 N增加到11 N）。掺杂锌的CaP涂层表现出增强的耐腐蚀性和增加的生物矿化。RNA测序显示，添加锌抑制了炎症并促进了耐受性巨噬细胞编程。最显著的影响是锌对愈合巨噬细胞中CaP抑制的氧化磷酸化和溶酶体途径的补偿作用，以及金属硫蛋白的上调。掺杂锌的涂层还表现出优异的抗菌效果，分别将大肠杆菌和金黄色葡萄球菌的定植减少了99%和90%。
Ti64植入物上的掺杂锌的CaP涂层显著提高了耐腐蚀性、生物活性和抗菌性能。我们开发了一种先进的多功能生物材料，其具有有益的抗炎和先天免疫组织整合编程，为长期植入物整合提供了主要优势，并降低了植入物失败的风险。
