Helmholtz-Zentrum hereon GmbH, Institute of Metallic Biomaterials, Max-Planck-Straße 1, Geesthacht 21502, Germany.
Helmholtz-Zentrum hereon GmbH, Institute of Metallic Biomaterials, Max-Planck-Straße 1, Geesthacht 21502, Germany.
Acta Biomater. 2024 Sep 1;185:41-54. doi: 10.1016/j.actbio.2024.06.040. Epub 2024 Jul 4.
The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. STATEMENT OF SIGNIFICANCE: Degradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups.
免疫系统在骨折愈合中起着重要作用，通过调节受伤后即刻发生的促炎和抗炎反应。这些反应的失衡可能导致不良后果，如骨折不愈合。植入物用于支撑和稳定复杂的骨折。与不可降解的植入物相比，可生物降解的金属植入物具有避免二次手术取出植入物的潜力。然而，考虑到我们动态的免疫系统，在活体系统中深入研究这些植入物的免疫反应非常重要。在这项研究中，我们在大鼠股骨骨折模型中使用外固定器研究了 Mg 和 Mg-10Gd 的体内免疫反应。使用脂质体制剂进行体内成像，以随时间监测荧光相关的炎症。我们将体外方法与体内研究相结合，以评估和理解植入物对免疫反应的全身和局部影响。与 SHAM 和 Mg 植入组相比，我们在 Mg-10Gd 植入组中未观察到随时间推移的明显局部或全身影响。我们的研究结果表明，与 Mg 相比，Mg-10Gd 是一种更具相容性的植入材料，在我们的 4 周研究中，在骨折愈合的早期阶段未观察到不良反应。研究意义：以 Mg 和 Mg-10Gd 髓内钉形式的可降解金属植入物在大鼠股骨骨折模型中进行了评估，与未植入的 SHAM 组一起，特别关注其诱导炎症反应的潜力。这项临床前研究结合了创新的非侵入性体内成像技术和多模式的体外细胞和分子分析。该研究有助于可降解生物金属的开发和评估及其临床应用潜力。研究结果表明，与 SHAM 和 Mg 组相比，Mg-10Gd 没有表现出任何显著的有害影响。
