Smith Matthew J, White Kimber L, Smith Donna C, Bowlin Gary L
Department of Biomedical Engineering, 401 W. Main Street, PO Box 843067, Virginia Commonwealth University, Richmond, VA 23284-3067, USA.
Biomaterials. 2009 Jan;30(2):149-59. doi: 10.1016/j.biomaterials.2008.09.019. Epub 2008 Oct 11.
Immune response testing of biomaterials is an essential component of biocompatibility assessment, particularly when the materials of interest are used to design bioresorbable scaffolds with the potential to promote in situ regeneration. Current trends in immune response testing of biomaterials typically examine few elements of the immune system, and they often undertake a mechanistic approach without first determining if material exposure results in physiologically relevant modulation of both innate and acquired immunity. Here, we present a comprehensive in vitro evaluation of biomaterial-induced modulation of acquired (i.e. cell-mediated and humoral) and innate immune responses following exposure to electrospun blends of polydioxanone (PDO) and elastin (ELAS). Results indicated that in vitro exposure of murine spleen cells to PDO-ELAS blends produced statistically significant immunosuppression in multiple cell-mediated and humoral endpoints. Results suggested that ELAS is the primary cause of cell-mediated immunosuppression. In contrast, PDO and ELAS were equally suppressive of humoral immune responses, while blends of the two were more immunosuppressive than either pure polymer alone. Evaluations of innate immune responses demonstrated few significant effects, with statistically significant immunosuppression observed in natural killer cell activity but not in macrophage functional assays. This work presents an approach for assessing potential modulation of immune responses resulting from exposure to biomaterials, and such evaluations are essential to obtaining comprehensive assessments of biocompatibility.
生物材料的免疫反应测试是生物相容性评估的重要组成部分，特别是当所关注的材料用于设计具有促进原位再生潜力的可生物降解支架时。生物材料免疫反应测试的当前趋势通常只检查免疫系统的少数元素，并且它们常常采用机械方法，而没有首先确定材料暴露是否会导致先天免疫和后天免疫的生理相关调节。在此，我们展示了对聚二氧六环酮（PDO）和弹性蛋白（ELAS）的电纺共混物暴露后生物材料诱导的后天（即细胞介导和体液）和先天免疫反应调节的全面体外评估。结果表明，将小鼠脾细胞体外暴露于PDO-ELAS共混物在多个细胞介导和体液终点产生了具有统计学意义的免疫抑制。结果表明，ELAS是细胞介导的免疫抑制的主要原因。相比之下，PDO和ELAS对体液免疫反应的抑制作用相同，而两者的共混物比单独的任何一种纯聚合物更具免疫抑制性。先天免疫反应的评估显示几乎没有显著影响，在自然杀伤细胞活性中观察到具有统计学意义的免疫抑制，但在巨噬细胞功能测定中未观察到。这项工作提出了一种评估暴露于生物材料导致的免疫反应潜在调节的方法，并且这种评估对于获得生物相容性的全面评估至关重要。
