Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection.
Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection.
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DOI：
10.1016/j.jconrel.2010.05.032
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Babensee JE
中科院分区：
文献类型：
--
作者：
Norton LW;Park J;Babensee JE
生物材料已被证明在不同程度上支持树突状细胞(DC)成熟，这是佐剂作用的先决条件。聚(D，L-乳酸-羟基乙酸共聚)处理树突状细胞(PLGA)膜能促进DC成熟，而琼脂糖膜不能。在这些研究中，生物材料的佐剂效应通过材料选择(PLGA或琼脂支架)或从PLGA支架局部输送抗炎/免疫抑制糖皮质激素地塞米松(DX)来减弱。制备了PLGA或琼脂糖多孔支架(SCs)，以传递等量的模型抗原-卵清蛋白(OVA)。或者，用或不用DX生产掺入OVA的PLGA SCs。将这些干细胞单独、皮下和背部植入C57BL/6小鼠体内。在12周的持续时间内，在特定的时间从小鼠身上采集血液，以测量针对OVA的抗体产生。12周时植入支架，进行异物反应的组织学检查。与阴性对照相比，PLGA支架，而不是琼脂糖支架，被发现能够诱导更高的抗体产量来对抗联合传递OVA。短期注射DX的PLGA SCs可暂时延迟抗OVA抗体的产生。在有效剂量和适当的时间过程中，DX的更持久的释放有望延长DX对生物材料佐剂效应的影响。生物材料的免疫调节能力影响对共传递抗原的免疫反应，其中这种免疫调节能力与观察到的生物材料对DC成熟的体外差异效应相关。
Biomaterials have been shown to differentially support dendritic cell (DC) maturation, a prerequisite for an adjuvant effect. Treatment of DCs with poly(D,L-lactic-co-glycolic acid). (PLGA) films resulted in DC maturation but agarose films did not. In these studies, the biomaterial adjuvant effect was attenuated by material selection (PLGA or agarose scaffolds) or local delivery of an anti-inflammatory/immunosuppressive glucocorticoid, dexamethasone (DX), from PLGA scaffolds. Porous scaffolds (SCs) of PLGA or agarose were produced to deliver equivalent amounts of model antigen, ovalbumin (OVA). Alternatively, PLGA SCs with incorporated OVA were produced with or without DX. These SCs were implanted individually, subcutaneously, and dorsally in C57BL/6 mice. Blood was collected from mice at specific times over a 12-week duration for measurement of antibody production against OVA. Scaffolds were explanted at 12 weeks for histological examination of foreign body response. Scaffolds of PLGA, but not of agarose, were found to elicit higher antibody production against co-delivered OVA, than negative controls. Short term delivery of DX from PLGA SCs delivering OVA temporarily delayed onset of anti-OVA antibody production. More sustained release of DX at an effective dose and with an appropriate time course is expected to extend the effect of DX on the biomaterial adjuvant effect. The immunomodulatory ability of biomaterials to affect the immune response to co-delivered antigen is demonstrated wherein this immunomodulatory ability correlates with the observed in vitro differential effects of biomaterials on DC maturation.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1196/annals.1321.009
发表时间：
2004-01-01
期刊：
GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS
影响因子：
--
作者：
Franchimont, D
通讯作者：
Franchimont, D
影响因子：
5.1
作者：
Lü JM;Wang X;Marin-Muller C;Wang H;Lin PH;Yao Q;Chen C
通讯作者：
Chen C
影响因子：
15.9
作者：
Kitajima, T;Ariizumi, K;Takashima, A
通讯作者：
Takashima, A
影响因子：
--
作者：
Beer, H D;Fassler, R;Werner, S
通讯作者：
Werner, S