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Inflammatory responses and tissue reactions to wood-Based nanocellulose scaffolds

机译:对木质纳米纤维素支架的炎症反应和组织反应

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Two wood-derived cellulose nanofibril (CNF) porous scaffolds were prepared by TEMPO-oxidation and carboxymethylation. The effects of these scaffolds on the production of inflammatory cytokines by human macrophage-like cells (U937) was profiled in vitro after 1 and 3 days and in subcutaneous tissues of rats after 4 and 30 days, using PCR and Multiplex arrays. Tissue culture plates (TCP) and gelatin scaffolds served as controls in vitro and in vivo respectively. After 3 days in vitro, there was no significant difference between the effects of CNF scaffolds and TCP on the production of chemokines/growth factors and pro-inflammatory cytokines. At day 4 in vivo there was significantly higher gene expression of the anti-inflammatory IL-1Ra in the CNF scaffolds than the gelatin scaffold. Production of IL-1 beta, IL-6, MCP-1, MIP-1 alpha CXCL-1 and M-CSF was significantly less than in the gelatin, demonstrating an early mild inflammatory response. At day 30, both CNF scaffolds significantly stimulated the production of the anti-inflammatory cytokine IL-10. Unlike gelatin, neither CNF scaffold had degraded 180 days post-implantation. The slow degradation of CNF scaffolds resulted in a foreign body reaction, with high production of IL-1 beta, IL-2, TNF-alpha, IFN-gamma, MCP-1, MIP-1 alpha, M-CSF, VEGF cytokines and expression of MMP-9 gene. The surface chemistry of the CNF scaffolds elicited a modest effect on cytokine production and did not shift the inflammatory profile in vitro or in vivo. The decisive role in development of the foreign body reaction was the slow degradation of the CNF scaffolds.
机译:通过TEMPO氧化和羧甲基化制备了两种木材衍生的纤维素纳米原纤维(CNF)多孔支架。使用PCR和Multiplex阵列,在1和3天后体外和在大鼠的皮下组织中分析这些支架对人巨噬细胞样细胞(U937)产生炎性细胞因子的作用。组织培养板(TCP)和明胶支架分别用作体外和体内的对照。在体外3天后,CNF支架和TCP对趋化因子/生长因子和促炎细胞因子的产生的影响没有显着差异。在体内第4天,CNF支架中抗炎IL-1Ra的基因表达明显高于明胶支架。 IL-1β,IL-6,MCP-1,MIP-1αCXCL-1和M-CSF的产生显着低于明胶,表明了早期的轻度炎症反应。在第30天,两种CNF支架均显着刺激了抗炎细胞因子IL-10的产生。与明胶不同,CNF支架在植入后180天均未降解。 CNF支架的缓慢降解导致异物反应,并大量产生IL-1β,IL-2,TNF-α,IFN-γ,MCP-1,MIP-1α,M-CSF,VEGF细胞因子和MMP-9基因的表达CNF支架的表面化学性质对细胞因子的产生引起适度的影响,并且在体外或体内均不改变炎性特征。在异物反应发展中的决定性作用是CNF支架的缓慢降解。

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