Abstract We propose silicone implants capable of the local, controlled release of a glucocorticoid drug, triamcinolone acetonide (TA), for the prevention of fibrosis. The shells of these silicone implants were coated with two different loading amounts of TA, which could release the drug in a sustained manner for 12 weeks. The drug-loaded implants were inserted into the subcutaneous space in living rats, and the tissues were biopsied at scheduled times during 12 weeks. For the drug-coated implants, the capsule thickness and collagen density decreased compared with those of the non-coated implant. Because of the effect of TA, inflammation and the expression of pro-inflammatory cytokines were downregulated, thereby decreasing the number of monocytes during acute inflammation. This effect in turn decreased the number of macrophages at the later stage of inflammation, leading to the expression of less TGF-β and consequently fewer fibroblasts and myofibroblasts. Our findings also revealed that with an appropriate dose control, skin and muscle atrophy, major side effects of TA, could be avoided while still effectively reducing fibrosis. Therefore, we conclude that the local, sustained release of an appropriate dose of a glucocorticoid drug can be a promising strategy for safely preventing fibrosis around silicone implants.

中文翻译：

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能够局部控制释放曲安西龙以预防纤维化并最大限度减少药物副作用的硅胶植入物

摘要 我们提出了一种能够局部控制释放糖皮质激素药物曲安奈德 (TA) 的硅胶植入物，用于预防纤维化。这些硅胶植入物的外壳涂有两种不同负载量的 TA，可以持续释放药物 12 周。将载药植入物插入活大鼠的皮下空间，并在 12 周内按预定时间对组织进行活检。对于药物涂层植入物，与未涂层植入物相比，胶囊厚度和胶原密度降低。由于 TA 的作用，炎症和促炎细胞因子的表达被下调，从而减少了急性炎症期间的单核细胞数量。这种作用反过来又减少了炎症后期巨噬细胞的数量，导致 TGF-β 表达减少，从而导致成纤维细胞和肌成纤维细胞减少。我们的研究结果还表明，通过适当的剂量控制，可以避免皮肤和肌肉萎缩以及 TA 的主要副作用，同时仍能有效减少纤维化。因此，我们得出结论，适当剂量的糖皮质激素药物的局部持续释放可能是安全预防硅胶植入物周围纤维化的有前途的策略。