Liu Lingyun, Chen Gang, Chao Timothy, Ratner Buddy D, Sage E Helene, Jiang Shaoyi
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
J Biomater Sci Polym Ed. 2008;19(6):821-35. doi: 10.1163/156856208784522083.
The foreign body reaction (FBR), which leads to the encapsulation of implanted biomaterials, has been implicated in the failure of many medical devices. The protein layer that is nonspecifically adsorbed onto the implant surface immediately after implantation is thought to dictate this reaction. It is hypothesized that biomaterial surfaces having specific proteins with precisely controlled orientations will decrease the FBR. Previously, we have reported that osteopontin (OPN) adsorbed on positively charged surfaces has a preferable orientation for in vitro cell adhesion and spreading as compared to negatively charged surfaces. It is expected that coating a layer of OPN in its preferred orientation on an implant surface will decrease the FBR. In this work, in vivo studies were performed to test this hypothesis. A positively charged polymer (p(HEMA-co-AEMA)) and a negatively charged polymer (p(HEMA-co-CEA)) coated with OPN were implanted subcutaneously in wild-type mice for 7 or 28 days. Uncoated polymers were used as control. For the 7-day implants, cells on OPN-coated p(HEMA-co-AEMA) spread more than cells on the other three materials. Following 28 days of implantation the implants were explanted and the capsule thickness and vascularity around the implants were characterized. Additionally, the macrophage and foreign body giant cells (FBGCs) around the implants were quantified. It was found in this study that the modification of the positively charged polymer surface with OPN in a controlled orientation led to a reduction in the foreign body reaction as determined by capsule thickness. Our finding provides valuable information for designing better biocompatible biomaterials with improved in vivo performance.
异物反应（FBR）会导致植入生物材料被包裹，这与许多医疗设备的失效有关。植入后立即非特异性吸附在植入物表面的蛋白质层被认为决定了这种反应。据推测，具有精确控制取向的特定蛋白质的生物材料表面将减少FBR。此前，我们曾报道，与带负电的表面相比，吸附在带正电表面的骨桥蛋白（OPN）在体外细胞黏附和铺展方面具有更优的取向。预计在植入物表面以其优选取向涂覆一层OPN将减少FBR。在这项工作中，进行了体内研究以验证这一假设。将涂覆有OPN的带正电聚合物（p(HEMA-co-AEMA)）和带负电聚合物（p(HEMA-co-CEA)）皮下植入野生型小鼠体内7天或28天。未涂覆的聚合物用作对照。对于7天的植入物，OPN涂覆的p(HEMA-co-AEMA)上的细胞比其他三种材料上的细胞铺展得更多。植入28天后，将植入物取出并对植入物周围的囊厚度和血管化进行表征。此外，对植入物周围的巨噬细胞和异物巨细胞（FBGCs）进行定量。在本研究中发现，以可控取向用OPN对带正电聚合物表面进行修饰可导致异物反应降低，这由囊厚度确定。我们的发现为设计具有更好体内性能的生物相容性更好的生物材料提供了有价值的信息。
