Papadimitriou Lina, Kaliva Maria, Vamvakaki Maria, Chatzinikolaidou Maria
Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), 71110 Heraklion, Greece.
Department of Materials Science and Technology, University of Crete, 71001 Heraklion, Greece.
ACS Biomater Sci Eng. 2017 Jul 10;3(7):1341-1349. doi: 10.1021/acsbiomaterials.6b00440. Epub 2016 Nov 23.
In tissue engineering, the use of biomaterials as templates or scaffolds to guide tissue development in vivo provokes the inevitable action of the immune system of the host. This induced immune response often determines the success of the scaffold, including angiogenesis and regeneration or failure causing inflammation and fibrosis. Therefore, it is crucial to predict or even better to promote the proper immune response following implantation. The aim of the present study was to evaluate the immunomodulatory potential of chitosan--poly(ε-caprolactone) copolymers (CS--PCL) by analyzing the differentiation of primary bone marrow derived macrophages (BMDM) cultured in vitro on copolymer thin films. In order to evaluate the role of the chitosan content of the copolymer on macrophage polarization, two different copolymers containing 50 and 78% w/w chitosan were studied. Our data from cytokines secretion detection by ELISA show that the CS--PCL copolymer significantly decreases the secretion of the inducible levels of pro-inflammatory cytokines IL-12/23 by 31% ± 6, and thus possesses anti-inflammatory ability. Moreover, this anti-inflammatory action is correlated with the increased chitosan content of the copolymer. In addition, the CS--PCL copolymer significantly enhances the production of Arg1, the hallmark of M2 polarized macrophages, as shown by semiquantitative RT-PCR analysis, and this enhancement is 4-fold higher for the copolymer with the lower chitosan content. Although further in vivo experimentation is required to predict the outcome of the in situ engraftment of the copolymer, our results so far suggest that the CS--PCL copolymers possess anti-inflammatory activity and favor the transition of M1 to M2 macrophages, which are essential prerequisites for proper tissue remodeling.
在组织工程中，使用生物材料作为模板或支架来引导体内组织发育会引发宿主免疫系统的必然反应。这种诱导的免疫反应通常决定了支架的成败，包括血管生成和再生或导致炎症和纤维化的失败。因此，预测甚至更好地促进植入后适当的免疫反应至关重要。本研究的目的是通过分析在共聚物薄膜上体外培养的原代骨髓来源巨噬细胞（BMDM）的分化，评估壳聚糖-聚（ε-己内酯）共聚物（CS-PCL）的免疫调节潜力。为了评估共聚物中壳聚糖含量对巨噬细胞极化的作用，研究了两种不同的壳聚糖含量分别为50%和78%（w/w）的共聚物。我们通过ELISA检测细胞因子分泌的数据表明，CS-PCL共聚物可使促炎细胞因子IL-12/23的诱导水平分泌显著降低31%±6，因此具有抗炎能力。此外，这种抗炎作用与共聚物中壳聚糖含量的增加相关。另外，如半定量RT-PCR分析所示，CS-PCL共聚物显著增强了M2极化巨噬细胞的标志Arg1的产生，对于壳聚糖含量较低的共聚物，这种增强作用高4倍。尽管需要进一步的体内实验来预测共聚物原位植入的结果，但我们目前的结果表明，CS-PCL共聚物具有抗炎活性，并有利于M1向M2巨噬细胞的转变，这是适当组织重塑的重要先决条件。
