Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Biomaterials Group, Materials Design Division, Faculty of Materials Science and Engineering, Warsaw University of Technology, Poland.
Biomaterials. 2025 Mar;314:122779. doi: 10.1016/j.biomaterials.2024.122779. Epub 2024 Aug 30.
Orthopedic implants made of biodegradable magnesium (Mg) provide an alternative to nondegradable implants for fracture repair. Widely reported to be pro-osteogenic, Mg implants are also believed to be anti-inflammatory and anti-osteoclastic, but this is difficult to reconcile with the early clinical inflammation observed around these implants. Here, by surveying implant healing in a rat bone model, we determined the cellular responses and structural assembly of bone correlated with the surface changes of Mg implants inherent in degradation. We show that, compared to titanium, both high-purity (99.998 %) and clinical-grade, rare earth-alloyed (MgYREZr) Mg implants create an initial, transient proinflammatory environment that facilitates inducible nitric oxide synthase-mediated macrophage polarization, osteoclastogenesis, and neoangiogenesis programs. While this immunomodulation subsequently reinforces reparative osteogenesis at the surface of both Mg implants, the faster degradation of high-purity Mg implants, but not MgYREZr implants, elicits a compositional alteration in the interfacial bone and a previously unknown proadipogenic response with persistent low-grade inflammation in the surrounding bone marrow. Beyond the need for rigorous tailoring of Mg implants, these data highlight the need to closely monitor osseointegration not only at the immediate implant surface but also in the peri-implant bone and adjacent bone marrow.
可生物降解镁（Mg）制成的骨科植入物为骨折修复提供了一种替代不可降解植入物的方法。据广泛报道，Mg 植入物具有促成骨作用，同时也具有抗炎和抗破骨作用，但这很难与早期临床观察到的这些植入物周围的炎症相协调。在这里，通过在大鼠骨模型中调查植入物愈合情况，我们确定了与降解过程中 Mg 植入物表面变化相关的细胞反应和骨的结构组装。我们表明，与钛相比，高纯（99.998%）和临床级、稀土合金（MgYREZr）Mg 植入物都会产生初始的、短暂的促炎环境，从而促进诱导型一氧化氮合酶介导的巨噬细胞极化、破骨细胞生成和新血管生成程序。虽然这种免疫调节随后在两种 Mg 植入物的表面加强了修复性成骨作用，但高纯 Mg 植入物的降解速度更快，而 MgYREZr 植入物则不会，这会导致界面骨的成分发生变化，并出现以前未知的促脂肪生成反应，导致周围骨髓持续低度炎症。除了需要严格调整 Mg 植入物外，这些数据还强调需要不仅密切监测即刻植入物表面，而且还需要密切监测植入物周围骨和相邻骨髓中的骨整合情况。
