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Electron-beam surface modification of bioresorbable polymers for enhanced release of silver nano-particles: an anti-bacterial strategy

机译:生物吸收性聚合物的电子束表面改性以增强银纳米颗粒的释放:一种抗菌策略

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Introduction: Interest is developing in manipulating bioresorbable polymers with regards to biofitm prevention which can help alleviate major implant complications such as infection and implant removal. Previous work has shown that near-surface modification of bioresorbable polymers can be achieved via low energy electron beam (e-beam) irradiationFl which enhances the release of bioactive additives.An additive which has previously shown potential as an antimicrobial is silver nano-particles.It is hypothesized that the e-beam treatment will reduce biofilm formation via controlled release of silver nano-particles. The aim of this study was to utilise low energy e-beam irradiation to initiate preferential surface degradation of a clinically relevant bioresorbable polymer, focusing on mechanisms for biofilm prevention. Materials and Methods: Poly(lactide-co-glycolide) (PLG) sheets (Purac PURASORB PLG 8531), loaded with 0,1 and 2 wt% silver nano-particles (SNP), particle size: 20-40nm (QuantumSphere, USA) were produced by melt-extrusion compounding followed by compression moulding. Samples of 010 × 1mm were cut from these sheets. Two sets of samples were irradiated at Rise HDRL, Technical University of Denmark, at an energy of 125keV and doses of 150kGy and 450kGy. Following e-beam treatment, irradiated and non-irradiated samples were subjected to a 28 day static degradation study. Samples were placed in Phosphate Buffered Saline (PBS) solution (pH of 7.4) and held at 47°C (to accelerate degradation kinetics). During the study silver release was monitored using inductively coupled plasma spectroscopy (ICP) at time points of 3,7,17 and 28 days. Using gram positive bacteria, Staphylococcus aureus, static biofilm adherence testing was carried out on non-degraded and pre-degraded samples in order to ascertain the degree of biofilm inhibition. Results and Discussion: Figure 1 shows the silver release during degradation testing (1 and 2% wt SNP loading). Significantly higher levels of silver release (approximately ten times) were observed for electron beam irradiated specimens compared to non-irradiated (Nl) controls at 17 and 28 days. Figure 2 shows that samples with a 2% wt SNP loading, irradiated at 450kGy and statically pre-degraded for 7 days, did show a viable reduction in Staphylococcus aureus attachment compared to samples subjected to the same irradiation treatment and pre-degradation but with 0% wt SNP loading. This corresponded to an approximate reduction in colony forming units of 90%. No viable reduction In attachment was evident for non-irradiated samples (Nl) or samples irradiated at 150kGy. Figure 3 shows corresponding images of bacterial colony growth for 7 days pre-degraded specimens (0% and 2% SNP, 450 kGy). The results suggest that bacterial inhibition is influenced positively by SNP release but negatively by the physical condition of the degraded polymer. It would seem that one factor may nullify the other. Conclusion: This work has shown that low energy e-beam treatment can modify bioactive release by up to one order of magnitude. Furthermore irradiated SNP loaded PLG exhibited microbial inhibition when compared to irradiated, non-SNP loaded PLG. It is proposed that the use of an antimicrobial in conjunction with irradiation treatment has potential benefits for applications where antimicrobial efficacy is required.
机译:简介:在预防生物适应性方面,人们对操纵可生物吸收性聚合物的兴趣正在增强,这有助于减轻植入物的主要并发症,例如感染和植入物的去除。先前的工作表明,可生物吸收性聚合物的近表面改性可通过低能电子束(e-beam)辐照F1来实现,该辐照可增强生物活性添加剂的释放。以前显示出作为抗菌剂潜力的添加剂是银纳米颗粒。假设电子束处理将通过控制释放银纳米颗粒来减少生物膜的形成。这项研究的目的是利用低能电子束辐照引发临床相关生物可吸收聚合物的优先表面降解,重点是预防生物膜的机制。材料和方法:聚丙交酯-乙交酯共聚物(PLG)片(Purac PURASORB PLG 8531),载有0.1和2重量%的银纳米粒子(SNP),粒径:20-40nm(美国QuantumSphere) )是通过熔融挤出复合然后进行压塑而生产的。从这些薄片上切下010×1mm的样品。在丹麦技术大学的Rise HDRL上以125keV的能量和150kGy和450kGy的剂量辐照了两组样品。电子束处理后,对经过辐照和未经辐照的样品进行28天静态降解研究。将样品置于磷酸盐缓冲盐水(PBS)溶液(pH值为7.4)中,并保持在47°C下(以加速降解动力学)。在研究期间,使用电感耦合等离子体光谱法(ICP)在3、7、17和28天的时间点监测银的释放。使用革兰氏阳性细菌,金黄色葡萄球菌,对未降解和预降解的样品进行了静态生物膜附着力测试,以确定生物膜的抑制程度。结果与讨论:图1显示了降解测试期间的银释放(1和2%wt SNP负载)。在17天和28天,与未辐照(N1)对照相比,电子束辐照的样品观察到明显更高的银释放水平(大约十倍)。图2显示,以25%wt的SNP负载的样品在450kGy辐射下进行了7天的静态预降解,与经过相同的辐射处理和预降解但0的样品相比,金黄色葡萄球菌的附着力确实降低了SNP含量%wt。这相当于菌落形成单位的大约减少了90%。对于未辐照样品(N1)或以150kGy辐照的样品,附着力没有明显降低。图3显示了7天预降解标本(0%和2%SNP,450 kGy)的细菌菌落生长的相应图像。结果表明,细菌抑制受到SNP释放的积极影响,但受降解聚合物的物理条件的不利影响。似乎一个因素可能会使另一个因素无效。结论:这项工作表明,低能电子束治疗可以将生物活性释放提高一个数量级。此外,与辐照的,非SNP的PLG相比,辐照的SNP的PLG表现出了微生物抑制作用。提出将抗微生物剂与辐射治疗结合使用对于需要抗微生物功效的应用具有潜在的益处。

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