Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive Atlanta, GA 30332, USA.
J Control Release. 2010 Sep 15;146(3):341-8. doi: 10.1016/j.jconrel.2010.05.032. Epub 2010 Jun 2.
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.
生物材料已被证明可以差异化地支持树突状细胞 (DC) 的成熟,这是佐剂效应的前提。用聚 (D,L-丙交酯-共-乙交酯) (PLGA) 薄膜处理 DC 会导致 DC 成熟,但琼脂糖薄膜则不会。在这些研究中,通过材料选择 (PLGA 或琼脂糖支架) 或从 PLGA 支架局部递送抗炎/免疫抑制性糖皮质激素地塞米松 (DX) 来减弱生物材料佐剂效应。制备了 PLGA 或琼脂糖的多孔支架 (SC) 以递送等量的模型抗原卵清蛋白 (OVA)。或者,用或不用 DX 制备了掺入 OVA 的 PLGA SC。这些 SC 单独植入 C57BL/6 小鼠的皮下和背部。在 12 周的时间内,从小鼠采集血液以测量针对 OVA 的抗体产生。在 12 周时取出支架,进行异物反应的组织学检查。发现 PLGA 支架而不是琼脂糖支架会引起针对共递送 OVA 的更高抗体产生,而不是阴性对照。从递送 OVA 的 PLGA SC 短期递送至 DX 暂时延迟了抗 OVA 抗体产生的发生。预计以有效剂量和适当的时间过程更持续地释放 DX 将延长 DX 对生物材料佐剂效应的影响。生物材料调节免疫应答共递抗原的能力得到了证明,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。