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用甲基丙烯酸明胶对聚(D,L-丙交酯)微球进行表面改性:吸附、包封及氧等离子体处理方法的评估

Surface modification of PdlLGA microspheres with gelatine methacrylate: Evaluation of adsorption, entrapment, and oxygen plasma treatment approaches.

作者信息

Baki Abdulrahman, Rahman Cheryl V, White Lisa J, Scurr David J, Qutachi Omar, Shakesheff Kevin M

机构信息

Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

出版信息

Acta Biomater. 2017 Apr 15;53:450-459. doi: 10.1016/j.actbio.2017.01.042. Epub 2017 Jan 16.

Abstract

UNLABELLED

Injectable poly (dl-lactic-co-glycolic acid) (PdlLGA) microspheres are promising candidates as biodegradable controlled release carriers for drug and cell delivery applications; however, they have limited functional groups on the surface to enable dense grafting of tissue specific biocompatible molecules. In this study we have evaluated surface adsorption, entrapment and oxygen plasma treatment as three approaches to modify the surfaces of PdlLGA microspheres with gelatine methacrylate (gel-MA) as a biocompatible and photo cross-linkable macromolecule. Time of flight secondary ion mass spectroscopy (TOF SIMS) and X-ray photoelectron spectroscopy (XPS) were used to detect and quantify gel-MA on the surfaces. Fluorescent and scanning electron microscopies (SEM) were used to image the topographical changes. Human mesenchymal stem cells (hMSCs) of immortalised cell line were cultured on the surface of gel-MA modified PdlLGA microspheres and Presto-Blue assay was used to study the effect of different surface modifications on cell proliferation. Data analysis showed that the oxygen plasma treatment approach resulted in the highest density of gel-MA deposition. This study supports oxygen plasma treatment as a facile approach to modify the surface of injectable PdlLGA microspheres with macromolecules such as gel-MA to enhance proliferation rate of injected cells and potentially enable further grafting of tissue specific molecules.

STATEMENT OF SIGNIFICANCE

Poly (dl lactic-co-glycolic) acid (PdlLGA) microspheres offer limited functional groups on their surface to enable proper grafting of tissue specific bioactive molecules. To overcome this limitation, previous approaches have suggested using alkaline solutions to introduce active groups to the surface; however, they may compromise surface topography and lose any potential surface patterns. Plasma polymerisation of bioactive monomers has been suggested to enhance surface biocompatibility; however, it is not applicable on low vapour pressure macromolecules such as most extracellular matrix (ECM) proteins and growth factors. This study aims to evaluate three different approaches to modify the surface of PdlLGA microspheres with gelatine-methacrylate (gel-MA) to enable further grafting of cross-linkable biomolecules without compromising the surface topography or the biocompatibility of the system.

摘要

未标记

可注射的聚(dl-乳酸-共-乙醇酸)(PdlLGA)微球作为用于药物和细胞递送应用的可生物降解控释载体很有前景;然而,它们表面的官能团有限,无法实现组织特异性生物相容性分子的密集接枝。在本研究中,我们评估了表面吸附、包封和氧等离子体处理这三种方法,以用甲基丙烯酸明胶(gel-MA)作为生物相容性和可光交联的大分子来修饰PdlLGA微球的表面。飞行时间二次离子质谱(TOF SIMS)和X射线光电子能谱(XPS)用于检测和量化表面上的gel-MA。荧光显微镜和扫描电子显微镜(SEM)用于成像形貌变化。将永生化细胞系的人间充质干细胞(hMSCs)培养在gel-MA修饰的PdlLGA微球表面,并使用Presto-Blue测定法研究不同表面修饰对细胞增殖的影响。数据分析表明,氧等离子体处理方法导致gel-MA沉积密度最高。本研究支持氧等离子体处理作为一种简便的方法,用诸如gel-MA之类的大分子修饰可注射PdlLGA微球的表面,以提高注射细胞的增殖速率,并有可能实现组织特异性分子的进一步接枝。

重要性声明

聚(dl-乳酸-共-乙醇酸)(PdlLGA)微球表面的官能团有限,无法实现组织特异性生物活性分子的适当接枝。为克服这一限制,先前的方法建议使用碱性溶液在表面引入活性基团;然而,它们可能会损害表面形貌并失去任何潜在的表面图案。有人建议对生物活性单体进行等离子体聚合以增强表面生物相容性;然而,它不适用于低蒸气压的大分子,如大多数细胞外基质(ECM)蛋白和生长因子。本研究旨在评估三种不同的方法,用甲基丙烯酸明胶(gel-MA)修饰PdlLGA微球的表面,以实现可交联生物分子的进一步接枝,同时不损害表面形貌或系统的生物相容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2266/5424780/cce2a08849c6/fx1.jpg

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