Department of Dental Biomaterials Science, Dental Research Institute and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
Biomed Mater. 2020 Sep 24;15(6):065007. doi: 10.1088/1748-605X/aba238.
Biomedical implants tend to induce fibrous encapsulation which can cause malfunction of devices and local discomfort of patients. The purpose of this study was to reduce foreign body-induced fibrous capsule formation by immunomodulation of macrophages. Polyethylene-glycol-grafted liposomes containing phosphatidylserine (PEG-PSLs) were used to modulate macrophages. Mixed cellulose ester (MCE) membranes coated with a PEG-PSLs-entrapped alginate-gelatin matrix were subcutaneously implanted into rats, and the thickness of the fibrous capsule around each MCE membrane was analyzed after four weeks. PEG-PSLs significantly reduced fibrous capsule thickness, while liposomes containing phosphatidylserine (PSLs) did not affect fibrosis. In in vitro assays, PEG-PSLs suppressed TGF-β1 secretion and multinucleated giant cell (MGC) formation in IL-4-treated RAW 264.7, a murine macrophage cell line. Although PSLs inhibited MGC formation, they exerted no effect on the secretion of TGF- β1, which is known to be an important factor in tissue fibrosis. Therefore, our results suggest that PEG-PSLs reduce fibrous capsule formation by mediating the suppression of TGF-β1 secretion from macrophages.
生物医学植入物往往会引起纤维囊包裹，这可能导致设备故障和患者局部不适。本研究旨在通过调节巨噬细胞来减少异物引起的纤维囊形成。聚乙二醇接枝磷脂酰丝氨酸（PEG-PSLs）的脂质体用于调节巨噬细胞。混合纤维素酯（MCE）膜用包被有聚乙二醇-PSLs 包封的藻酸盐-明胶基质的聚乙二醇-PSLs 进行涂层，并将其皮下植入大鼠体内，四周后分析每个 MCE 膜周围纤维囊的厚度。PEG-PSLs 显著降低了纤维囊的厚度，而含有磷脂酰丝氨酸（PSLs）的脂质体则不影响纤维化。在体外实验中，PEG-PSLs 抑制了 IL-4 处理的 RAW 264.7（一种鼠巨噬细胞系）中 TGF-β1 的分泌和多核巨细胞（MGC）的形成。虽然 PSLs 抑制了 MGC 的形成，但它们对 TGF-β1 的分泌没有影响，TGF-β1 是组织纤维化的重要因素。因此，我们的结果表明，PEG-PSLs 通过调节巨噬细胞中 TGF-β1 的分泌来减少纤维囊的形成。
