Stein Philipp, Vitavska Olga, Kind Peter, Hoppe Willi, Wieczorek Helmut, Schürer Nanna Y
Division of Dermatology, Department of Environmental Medicine and Health Theory, University of Osnabrück, Sedanstraße 115, 49090 Osnabrück, Germany.
Division of Animal Physiology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 11, 49076 Osnabrück, Germany.
J Dermatol Sci. 2015 Apr;78(1):26-33. doi: 10.1016/j.jdermsci.2015.01.012. Epub 2015 Feb 7.
Granulomatous reactions to poly-L-lactic acid (PLLA)-based filler have been described previously. Neither the biological background of these partly late-onset reactions or the desired augmenting effect of PLLA has been studied to date. Histological studies have revealed foreign body reactions and foreign body giant cell formation.
The aim of this study was to increase our knowledge about the biological mechanisms behind the augmenting effect of PLLA-based filler.
We characterised the cell infiltrate and collagen type of PLLA-treated tissue by immunofluorescence staining. The expression of genes related to collagen metabolism was determined.
CD68(+) macrophages were found next to PLLA. CD90(+) fibroblasts were found alongside. αSMA-positive structures indicated myofibroblasts and neovascularisation. Substantial collagen type III deposition was detected next to PLLA particles and collagen type I was found at the periphery of PLLA encapsulations. mRNA expression for collagen type I and III transcripts, as well as for TGFβ1 and TIMP1, was upregulated significantly.
PLLA-induced augmentation is most likely based on capsule formation orchestrating macrophages, (myo-)fibroblasts, and collagen type I and III fibres. We observed considerably slower degradation of PLLA particles than described previously. Thus PLLA particles were still retrievable 28 months after subcutaneous application.
先前已有关于对聚左旋乳酸(PLLA)填充剂的肉芽肿反应的描述。然而,这些部分迟发性反应的生物学背景以及PLLA预期的填充效果迄今尚未得到研究。组织学研究已揭示了异物反应和异物巨细胞形成。
本研究的目的是增进我们对基于PLLA的填充剂填充效果背后生物学机制的了解。
我们通过免疫荧光染色对PLLA处理组织中的细胞浸润和胶原类型进行了表征。测定了与胶原代谢相关基因的表达。
在PLLA旁边发现了CD68(+)巨噬细胞。同时还发现了CD90(+)成纤维细胞。αSMA阳性结构表明存在肌成纤维细胞和新血管形成。在PLLA颗粒旁边检测到大量III型胶原沉积,而在PLLA包囊周围发现了I型胶原。I型和III型胶原转录本以及TGFβ1和TIMP1的mRNA表达均显著上调。
PLLA诱导的填充效果很可能基于由巨噬细胞、(肌)成纤维细胞以及I型和III型胶原纤维共同参与的囊形成。我们观察到PLLA颗粒的降解比先前描述的要慢得多。因此,皮下注射28个月后仍可取出PLLA颗粒。