Utomo Lizette, Boersema Geesien S A, Bayon Yves, Lange Johan F, van Osch Gerjo J V M, Bastiaansen-Jenniskens Yvonne M
Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, Netherlands.
Biomed Mater. 2017 Mar 7;12(2):025006. doi: 10.1088/1748-605X/aa5cbc.
After implantation of a biomaterial, an inflammatory response involving macrophages is induced. The behavior of macrophages depends on their phenotype, and by directing macrophage polarization unwanted effects may be avoided. In this study, the possibility to modulate the behavior of macrophages activated by biomaterials was assessed in an in vitro model. Primary human monocytes were seeded on polyethylene terephthalate, polypropylene and polylactic acid yarns, and treated with medications frequently used by patients: rapamycin, dexamethasone, celecoxib or pravastatin. Modulation of the adhering macrophages with rapamycin resulted in a generally pro-inflammatory effect. Dexamethasone caused an overall anti-inflammatory effect on the macrophages cultured on either material, while celecoxib only affected macrophages adhering to polyethylene terephthalate and polylactic acid. Pravastatin increased the pro-inflammatory genes of macrophages cultured on polypropylene and polylactic acid. Pairwise comparison revealed that macrophages adhering to polylactic acid seemed to be more susceptible to phenotype modulation than when adhering to polypropylene or polyethylene terephthalate. The data show that macrophages activated by the biomaterials can be modulated, yet the degree of the modulatory capacity depends on the type of material. Combined, this model provides insights into the possibility of using a medication in combination with a biomaterial to direct macrophage behavior and thereby possibly avoid unwanted effects after implantation.
生物材料植入后会引发涉及巨噬细胞的炎症反应。巨噬细胞的行为取决于其表型，通过引导巨噬细胞极化可以避免不良影响。在本研究中，在体外模型中评估了调节生物材料激活的巨噬细胞行为的可能性。将原代人单核细胞接种在聚对苯二甲酸乙二酯、聚丙烯和聚乳酸纱线上，并用患者常用的药物进行处理：雷帕霉素、地塞米松、塞来昔布或普伐他汀。雷帕霉素对黏附的巨噬细胞的调节产生了总体上的促炎作用。地塞米松对在任何一种材料上培养的巨噬细胞都产生了总体抗炎作用，而塞来昔布仅影响黏附在聚对苯二甲酸乙二酯和聚乳酸上的巨噬细胞。普伐他汀增加了在聚丙烯和聚乳酸上培养的巨噬细胞的促炎基因。成对比较显示，黏附在聚乳酸上的巨噬细胞似乎比黏附在聚丙烯或聚对苯二甲酸乙二酯上时更容易受到表型调节。数据表明，生物材料激活的巨噬细胞可以被调节，但其调节能力的程度取决于材料类型。综合来看，该模型为使用药物与生物材料联合以引导巨噬细胞行为从而可能避免植入后不良影响的可能性提供了见解。
