Correia Clara R, Gaifem Joana, Oliveira Mariana B, Silvestre Ricardo, Mano João F
3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Biomater Sci. 2017 Feb 28;5(3):551-560. doi: 10.1039/c6bm00920d.
Macrophages play a crucial role in the biological performance of biomaterials, as key factors in defining the optimal inflammation-healing balance towards tissue regeneration and implant integration. Here, we investigate how different surface modifications performed on poly(l-lactic acid) (PLLA) films would influence the differentiation of human monocytes into macrophages. We tested PLLA films without modification, surface-modified by plasma treatment (pPLLA) or by combining plasma treatment with different coating materials, namely poly(l-lysine) and a series of proteins from the extracellular matrix: collagen I, fibronectin, vitronectin, laminin and albumin. While all the tested films are non-cytotoxic, differences in cell adhesion and morphology are observed. Monocyte-derived macrophages (MDM) present a more rounded shape in non-modified films, while a more elongated phenotype is observed containing filopodia-like and podosome-like structures in all modified films. No major differences are found for the expression of HLA-DR/CD80 and CD206/CD163 surface markers, as well as for the ability of MDM to phagocytize. Interestingly, MDM differentiated on pPLLA present the highest expression of MMP9. Upon differentiation, MDM in all surface modified films present lower amounts of IL-6 and IL-10 compared to non-modified films. After stimulating MDM with the potent pro-inflammatory agent LPS, pPLLA and poly(l-lysine) and fibronectin-modified films reveal a significant reduction in IL-6 secretion, while the opposite effect is observed with IL-10. Of note, in comparison to non-modified films, all surface modified films induce a significant reduction of the IL-6/IL-10 ratio, a valuable prognosticator of the pro- versus anti-inflammatory balance. These findings provide important insights into MDM-biomaterial interactions, while strengthening the need for designing immune-informed biomaterials.
巨噬细胞在生物材料的生物学性能中起着关键作用，是决定组织再生和植入物整合的最佳炎症 - 愈合平衡的关键因素。在此，我们研究了聚（L - 乳酸）（PLLA）薄膜上进行的不同表面改性如何影响人单核细胞向巨噬细胞的分化。我们测试了未改性的PLLA薄膜、经等离子体处理表面改性的（pPLLA）薄膜，以及通过将等离子体处理与不同涂层材料（即聚（L - 赖氨酸）和一系列细胞外基质蛋白：I型胶原、纤连蛋白、玻连蛋白、层粘连蛋白和白蛋白）相结合而改性的薄膜。虽然所有测试薄膜均无细胞毒性，但观察到细胞粘附和形态存在差异。单核细胞衍生的巨噬细胞（MDM）在未改性薄膜中呈现更圆润的形状，而在所有改性薄膜中观察到含有丝状伪足样和足体样结构的更细长的表型。在HLA - DR/CD80和CD206/CD163表面标志物的表达以及MDM的吞噬能力方面未发现重大差异。有趣的是，在pPLLA上分化的MDM呈现出最高的MMP9表达。分化后，与未改性薄膜相比，所有表面改性薄膜中的MDM分泌的IL - 6和IL - 10量更低。在用强效促炎剂LPS刺激MDM后，pPLLA以及聚（L - 赖氨酸）和纤连蛋白改性的薄膜显示IL - 6分泌显著减少，而IL - 10则呈现相反的效果。值得注意的是，与未改性薄膜相比，所有表面改性薄膜均导致IL - 6/IL - 10比值显著降低，这是促炎与抗炎平衡的一个有价值的预后指标。这些发现为MDM - 生物材料相互作用提供了重要见解，同时强化了设计免疫知情生物材料的必要性。
