一种用琼脂糖基水凝胶包覆多巴胺功能化钛表面以实现庆大霉素控释的新策略。
A Novel Strategy to Coat Dopamine-Functionalized Titanium Surfaces With Agarose-Based Hydrogels for the Controlled Release of Gentamicin.
作者信息
Soylu H Melis, Chevallier Pascale, Copes Francesco, Ponti Federica, Candiani Gabriele, Yurt Fatma, Mantovani Diego
机构信息
Department Biomedical Technologies, The Institute of Natural and Applied Sciences, Ege University, Bornova, Turkey.
Laboratory for Biomaterials and Bioengineering, Canada Research Chair Tier 1, Department of Min-Met-Materials Eng., University Hospital Research Center, Regenerative Medicine, Laval University, Quebec City, QB, Canada.
出版信息
Front Cell Infect Microbiol. 2021 Jun 10;11:678081. doi: 10.3389/fcimb.2021.678081. eCollection 2021.
INTRODUCTION
The use of spinal implants for the treatment of back disorders is largely affected by the insurgence of infections at the implantation site. Antibacterial coatings have been proposed as a viable solution to limit such infections. However, despite being effective at short-term, conventional coatings lack the ability to prevent infections at medium and long-term. Hydrogel-based drug delivery systems may represent a solution controlling the release of the loaded antibacterial agents while improving cell integration. Agarose, in particular, is a biocompatible natural polysaccharide known to improve cell growth and already used in drug delivery system formulations. In this study, an agarose hydrogel-based coating has been developed for the controlled release of gentamicin (GS).
METHODS
Sand blasted Ti6Al4V discs were grafted with dopamine (DOPA) solution. After, GS loaded agarose hydrogels have been produced and additioned with tannic acid (TA) and calcium chloride (CaCl) as crosslinkers. The different GS-loaded hydrogel formulations were deposited on Ti6Al4V-DOPA surfaces, and allowed to react under UV irradiation. Surface topography, wettability and composition have been analyzed with profilometry, static contact angle measurement, XPS and FTIR spectroscopy analyses. GS release was performed under pseudo-physiological conditions up to 28 days and the released GS was quantified using a specific ELISA test. The cytotoxicity of the produced coatings against human cells have been tested, along with their antibacterial activity against bacteria.
RESULTS
A homogeneous coating was obtained with all the hydrogel formulations. Moreover, the coatings presented a hydrophilic behavior and micro-scale surface roughness. The addition of TA in the hydrogel formulations showed an increase in the release time compared to the normal GS-agarose hydrogels. Moreover, the GS released from these gels was able to significantly inhibit growth compared to the GS-agarose hydrogels. The addition of CaCl to the gel formulation was able to significantly decrease cytotoxicity of the TA-modified hydrogels.
CONCLUSIONS
Due to their surface properties, low cytotoxicity and high antibacterial effects, the hereby proposed gentamicin-loaded agarose-hydrogels provide new insight, and represent a promising approach for the surface modification of spinal implants, greatly impacting their application in the orthopedic surgical scenario.
引言
脊柱植入物用于治疗背部疾病的应用在很大程度上受到植入部位感染发生率的影响。抗菌涂层已被提议作为限制此类感染的可行解决方案。然而,尽管传统涂层在短期内有效,但缺乏预防中长期感染的能力。基于水凝胶的药物递送系统可能是一种解决方案,它可以控制负载的抗菌剂的释放,同时改善细胞整合。特别是琼脂糖,是一种生物相容性天然多糖,已知可促进细胞生长,并且已用于药物递送系统配方中。在本研究中,已开发出一种基于琼脂糖水凝胶的涂层用于庆大霉素(GS)的控释。
方法
对喷砂处理的Ti6Al4V圆盘用多巴胺(DOPA)溶液进行接枝。之后,制备了负载GS的琼脂糖水凝胶,并添加单宁酸(TA)和氯化钙(CaCl)作为交联剂。将不同的负载GS的水凝胶配方沉积在Ti6Al4V-DOPA表面,并在紫外线照射下使其反应。通过轮廓仪、静态接触角测量、XPS和FTIR光谱分析对表面形貌、润湿性和组成进行了分析。在伪生理条件下进行GS释放长达28天,并使用特定的ELISA试验对释放的GS进行定量。测试了所制备涂层对人细胞的细胞毒性及其对细菌的抗菌活性。
结果
所有水凝胶配方均获得了均匀的涂层。此外,涂层呈现亲水性行为和微观表面粗糙度。与普通的GS-琼脂糖水凝胶相比,在水凝胶配方中添加TA显示出释放时间增加。此外,与GS-琼脂糖水凝胶相比,从这些凝胶中释放的GS能够显著抑制细菌生长。向凝胶配方中添加CaCl能够显著降低TA改性水凝胶的细胞毒性。
结论
由于其表面性质、低细胞毒性和高抗菌效果,本文提出的负载庆大霉素的琼脂糖水凝胶提供了新的见解,代表了一种用于脊柱植入物表面改性的有前景的方法,极大地影响了它们在骨科手术场景中的应用。