Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
J Control Release. 2015 Feb 28;200:125-37. doi: 10.1016/j.jconrel.2014.12.021. Epub 2014 Dec 18.
We propose the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation.
我们提出急性、局部抑制转化生长因子β（TGF-β），一种主要的促纤维化细胞因子，以减少硅酮植入物周围的纤维化。为此，我们制备了能够持续释放曲尼司特（TGF-β抑制剂）5 天或 15 天的硅酮植入物。我们在活大鼠中植入植入物 12 周后进行了组织学和免疫组织化学分析。与未经处理的硅酮植入物相比，囊厚度和胶原密度显著降低。值得注意的是，TGF-β的早期抑制影响了实际上发生在伤口愈合晚期的纤维化。这种变化可能归因于急性炎症反应期间早期 TGF-β介导的单核细胞募集减少。因此，在随后的炎症阶段，随着 TGF-β和成纤维细胞数量的减少，观察到分化的巨噬细胞显著减少，导致纤维囊形成减少。
