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Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials

机译:巨噬细胞表型作为植入生物衍生的外科网状材料植入后结构性重塑的预测因子

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Macrophages have been classified as having plastic phenotypes which exist along a spectrum between M1 (classically activated; pro-inflammatory) and M2 (alternatively activated; regulatory, homeostatic). To date, the effects of polarization towards an M1 or M2 phenotype have been studied largely in the context of response to pathogen or cancer. Recently, M1 and M2 macrophages have been shown to play distinct roles in tissue remodeling following injury. In the present study, the M1/M2 paradigm was utilized to examine the role of macrophages in the remodeling process following implantation of 14 biologically derived surgical mesh materials in the rat abdominal wall. In situ polarization of macrophages responding to the materials was examined and correlated to a quantitative measure of the observed tissue remodeling response to determine whether macrophage polarization is an accurate predictor of the ability of a biologic scaffold to promote constructive tissue remodeling. Additionally the ability of M1 and M2 macrophages to differentially recruit progenitor-like cells in vitro, which are commonly observed to participate in the remodeling of those ECM scaffolds which have a positive clinical outcome, was examined as a possible mechanism underlying the differences in the observed remodeling responses. The results of the present study show that there is a strong correlation between the early macrophage response to implanted materials and the outcome of tissue remodeling. Increased numbers of M2 macrophages and higher ratios of M2:M1 macrophages within the site of remodeling at 14 days were associated with more positive remodeling outcomes (r 2 = 0.525-0.686, p 0.05). Further, the results of the present study suggest that the constructive remodeling outcome may be due to the recruitment and survival of different cell populations to the sites of remodeling associated with materials that elicit an M1 vs. M2 response. Both M2 and M0 macrophage conditioned media were shown to have higher chemotactic activities than media conditioned by M1 macrophages (p 0.05). A more thorough understanding of these issues will logically influence the design of next generation biomaterials and the development of regenerative medicine strategies for the formation of functional host tissues.
机译:巨噬细胞已被归类为具有可塑性表型,其沿M1(经典激活;促炎性)和M2(可选激活;调节性,稳态)之间的频谱存在。迄今为止,已经在针对病原体或癌症的反应中大量研究了极化对M1或M2表型的影响。最近,已显示M1和M2巨噬细胞在损伤后的组织重塑中起不同的作用。在本研究中,M1 / M2范式用于检查巨噬细胞在大鼠腹壁植入14种生物学衍生的外科网状材料后在重塑过程中的作用。检查了巨噬细胞对材料的原位极化,并将其与观察到的组织重塑反应的定量测量联系起来,以确定巨噬细胞极化是否是生物支架促进建设性组织重塑能力的准确预测指标。此外,还检查了M1和M2巨噬细胞体外分化募集祖细胞样细胞的能力,这些能力通常被观察到参与那些临床结果呈阳性的ECM支架的重塑,作为观察到的差异的潜在机制重塑响应。本研究的结果表明,早期巨噬细胞对植入材料的反应与组织重塑的结果之间存在很强的相关性。在第14天,重塑位点内M2巨噬细胞数量的增加和M2:M1巨噬细胞比例的增加与更积极的重塑结果相关(r 2 = 0.525-0.686,p <0.05)。此外,本研究的结果表明,建设性的重塑结果可能是由于不同细胞群体向重塑部位的募集和存活而引起的,这些部位与引起M1对M2反应的物质有关。 M2和M0巨噬细胞条件培养基均显示出比M1巨噬细胞条件培养基更高的趋化活性(p <0.05)。对这些问题的更透彻理解将在逻辑上影响下一代生物材料的设计以及用于功能性宿主组织形成的再生医学策略的发展。

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