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PDMS 基硅酮植入物的双表面修饰以抑制包膜挛缩。

Dual surface modification of PDMS-based silicone implants to suppress capsular contracture.

机构信息

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.

出版信息

Acta Biomater. 2018 Aug;76:56-70. doi: 10.1016/j.actbio.2018.06.022. Epub 2018 Jun 14.

Abstract

UNLABELLED

In this study, we report a new physicochemical surface on poly(dimethylsiloxane) (PDMS)-based silicone implants in an effort to minimize capsular contracture. Two different surface modification strategies, namely, microtexturing as a physical cue and multilayer coating as a chemical cue, were combined to achieve synergistic effects. The deposition of uniformly sized microparticles onto uncured PDMS surfaces and the subsequent removal after curing generated microtextured surfaces with concave hemisphere micropatterns. The size of the individual micropattern was controlled by the microparticle size. Micropatterns of three different sizes (37.16, 70.22, and 97.64 μm) smaller than 100 μm were produced for potential application to smooth and round-shaped breast implants. The PDMS surface was further chemically modified by layer-by-layer (LbL) deposition of poly-l-lysine and hyaluronic acid. Short-term in vitro experiments demonstrated that all the PDMS samples were cytocompatible. However, lower expression of TGF-β and α-SMA, the major profibrotic cytokine and myofibroblast marker, respectively, was observed in only multilayer-coated PDMS samples with larger size micropatterns (70.22 and 97.64 μm), thereby confirming the synergistic effects of physical and chemical cues. An in vivo study conducted for 8 weeks after implantation in rats also indicated that PDMS samples with larger size micropatterns and multilayer coating most effectively inhibited capsular contracture based on analyses of tissue inflammation, number of macrophage, fibroblast and myofibroblast, TGF-β expression, collagen density, and capsule thickness.

STATEMENT OF SIGNIFICANCE

Although poly(dimethylsiloxane) (PDMS)-based silicone implants have been widely used for various applications including breast implants, they usually cause typical side effects called as capsular contracture. Prior studies have shown that microtexturing and surface coating could reduce capsular contracture. However, previous methods are limited in their scope for application, and it is difficult to obtain FDA approval because of the large and nonuniform size of the microtexture as well as the use of toxic chemical components. Herein, those issues could be addressed by creating a microtexture of size less than 100 m, with a narrow size distribution and using layer-by-layer deposition of a biocompatible polymer without using any toxic compounds. Furthermore, this is the first attempt to combine microtexture with multilayer coating to obtain synergetic effects in minimizing the capsular contracture.

摘要

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在这项研究中,我们报告了一种新的聚二甲基硅氧烷(PDMS)基硅酮植入物的物理化学表面,以尽量减少包膜挛缩。我们结合了两种不同的表面改性策略,即微形貌作为物理线索和多层涂层作为化学线索,以达到协同效应。将大小均匀的微粒子沉积到未固化的 PDMS 表面上,然后在固化后去除,从而产生具有凹半球微图案的微形貌表面。通过控制微粒子的大小,可以控制单个微图案的大小。我们制作了三种不同尺寸(37.16、70.22 和 97.64μm)的微图案,尺寸均小于 100μm,可用于光滑和圆形乳房植入物。PDMS 表面通过聚-L-赖氨酸和透明质酸的层层(LbL)沉积进一步进行化学改性。短期的体外实验表明,所有 PDMS 样品均具有细胞相容性。然而,仅在具有较大尺寸微图案(70.22 和 97.64μm)的多层涂覆 PDMS 样品中观察到 TGF-β和α-SMA 的表达降低,TGF-β和α-SMA 分别是主要的促纤维化细胞因子和肌成纤维细胞标志物,从而证实了物理和化学线索的协同作用。在大鼠体内进行了 8 周的植入物研究也表明,具有较大尺寸微图案和多层涂层的 PDMS 样品可有效抑制包膜挛缩,这基于组织炎症、巨噬细胞、成纤维细胞和肌成纤维细胞数量、TGF-β表达、胶原密度和囊厚度的分析。

意义声明

尽管基于聚二甲基硅氧烷(PDMS)的硅酮植入物已被广泛用于各种应用,包括乳房植入物,但它们通常会引起典型的副作用,称为包膜挛缩。先前的研究表明,微形貌和表面涂层可以减少包膜挛缩。然而,先前的方法在应用范围上受到限制,并且由于微形貌的尺寸大且不均匀,以及使用有毒的化学组分,因此很难获得 FDA 批准。在这里,可以通过创建尺寸小于 100μm、尺寸分布较窄的微形貌来解决这些问题,并使用生物相容性聚合物的层层沉积,而无需使用任何有毒化合物。此外,这是首次尝试将微形貌与多层涂层相结合,以在最小化包膜挛缩方面获得协同效应。

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