David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Biomaterials. 2011 Mar;32(7):1796-801. doi: 10.1016/j.biomaterials.2010.11.029. Epub 2010 Dec 13.
The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response.
植入生物材料后，非特异性宿主反应通常是医疗器械设计的关键挑战。为了评估生物相容性，测量炎症细胞对生物材料表面产生的活性氧（ROS）的释放是一种成熟的方法。然而，尚未证明对植入体内的材料检测 ROS。在这里，我们开发了一种生物发光全动物成像方法，以观察活体动物中对皮下植入材料的 ROS 释放。我们比较了两种代表性材料，聚苯乙烯和藻酸盐，在 28 天内 ROS 的实时生成。在聚苯乙烯植入物附近观察到高水平的 ROS，但藻酸盐植入物没有，并且在 28 天的过程中持续存在。组织学分析表明，高水平的 ROS 不仅与早期吞噬细胞的存在相关，而且与后期纤维化相关，表明 ROS 可能参与异物反应的急性和慢性阶段。这些数据是体内首次证明对植入材料产生 ROS，并描述了一种评估宿主反应的新方法。
