Srivastava Mrinal Gaurav, Kamarudin Nur Hidayatul Nazirah, Aktan Merve Kübra, Zheng Kai, Zayed Naiera, Yongabi Derick, Wagner Patrick, Teughels Wim, Boccaccini Aldo R, Braem Annabel
KU Leuven, Department of Materials Engineering (MTM), 3001 Leuven, Belgium.
Universiti Kebangsaan Malaysia, Department of Chemical and Process Engineering, Faculty of Engineering and Built Environment, Bangi 43600, Malaysia.
Pharmaceutics. 2024 Mar 8;16(3):377. doi: 10.3390/pharmaceutics16030377.
Peri-implantitis is a growing pathological concern for dental implants which aggravates the occurrence of revision surgeries. This increases the burden on both hospitals and the patients themselves. Research is now focused on the development of materials and accompanying implants designed to resist biofilm formation. To enhance this endeavor, a smart method of biofilm inhibition coupled with limiting toxicity to the host cells is crucial. Therefore, this research aims to establish a proof-of-concept for the pH-triggered release of chlorhexidine (CHX), an antiseptic commonly used in mouth rinses, from a titanium (Ti) substrate to inhibit biofilm formation on its surface. To this end, a macroporous Ti matrix is filled with mesoporous silica (together referred to as Ti/SiO), which acts as a diffusion barrier for CHX from the CHX feed side to the release side. To limit release to acidic conditions, the release side of Ti/SiO is coated with crosslinked chitosan (CS), a pH-responsive and antimicrobial natural polymer. Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDX) and Fourier transform infrared (FTIR) spectroscopy confirmed successful CS film formation and crosslinking on the Ti/SiO disks. The presence of the CS coating reduced CHX release by 33% as compared to non-coated Ti/SiO disks, thus reducing the antiseptic exposure to the environment in normal conditions. Simultaneous differential scanning calorimetry and thermogravimetric analyzer (SDT) results highlighted the thermal stability of the crosslinked CS films. Quartz crystal microbalance with dissipation monitoring (QCM-D) indicated a clear pH response for crosslinked CS coatings in an acidic medium. This pH response also influenced CHX release through a Ti/SiO/CS disk where the CHX release was higher than the average trend in the neutral medium. Finally, the antimicrobial study revealed a significant reduction in biofilm formation for the CS-coated samples compared to the control sample using viability quantitative polymerase chain reaction (v-qPCR) measurements, which were also corroborated using SEM imaging. Overall, this study investigates the smart triggered release of pharmaceutical agents aimed at inhibiting biofilm formation, with potential applicability to implant-like structures.
种植体周围炎是牙科种植体日益严重的病理问题，它加剧了翻修手术的发生。这增加了医院和患者自身的负担。目前的研究集中在开发旨在抵抗生物膜形成的材料及配套种植体。为推动这一努力，一种智能的生物膜抑制方法以及限制对宿主细胞的毒性至关重要。因此，本研究旨在建立一个概念验证，即从钛（Ti）基底触发释放洗必泰（CHX，一种常用在漱口液中的防腐剂），以抑制其表面生物膜的形成。为此，一个大孔Ti基体填充有介孔二氧化硅（统称为Ti/SiO），它作为CHX从进料侧到释放侧的扩散屏障。为了将释放限制在酸性条件下，Ti/SiO的释放侧涂覆有交联壳聚糖（CS），一种pH响应性和抗菌性天然聚合物。扫描电子显微镜结合能量色散X射线光谱（SEM/EDX）和傅里叶变换红外（FTIR）光谱证实了CS膜在Ti/SiO圆盘上成功形成和交联。与未涂覆的Ti/SiO圆盘相比，CS涂层的存在使CHX释放减少了33%，从而在正常条件下减少了防腐剂对环境的暴露。同步差示扫描量热法和热重分析仪（SDT）结果突出了交联CS膜的热稳定性。带有耗散监测的石英晶体微天平（QCM-D）表明交联CS涂层在酸性介质中有明显的pH响应。这种pH响应还通过Ti/SiO/CS圆盘影响CHX释放，其中CHX释放在中性介质中高于平均趋势。最后，抗菌研究表明，与使用活力定量聚合酶链反应（v-qPCR）测量的对照样品相比，CS涂覆样品的生物膜形成显著减少，这也通过SEM成像得到了证实。总体而言，本研究调查了旨在抑制生物膜形成的药物智能触发释放，具有对植入物样结构的潜在适用性。
