Karahaliloğlu Zeynep, Ercan Batur, Taylor Erik N, Chung Stanley, Denkbaş Emir B, Webster Thomas J
J Biomed Nanotechnol. 2015 Dec;11(12):2253-63. doi: 10.1166/jbn.2015.2106.
The principle of guided bone regeneration (GBR) in orthopedic, cranio-maxillofacial and dental tissue engineering applications is to create a secluded space for the treatment of large bone defects while excluding fibrous connective tissue formation at the defect area. In dental surgeries, a GBR membrane is placed near the dental implant in post-extraction sockets to grow new bone at the implant site, along with inhibiting infection due to the microbial nature of the mouth flora. Poly[(R)-3-hydroxybutyric acid] (PHB) is a natural polyester synthesized by a wide variety of microorganisms which has been proposed for various biomedical applications. In this study, to improve the performance of PHB as a GBR, a NaOH based alkaline treatment was designed to create nanofeatured PHB membranes. The newly fabricated nanofeatured PHB membranes were investigated for GBR applications. The results showed that a quick, simple, and inexpensive sodium hydroxide treatment modified the nanostructured surface morphology and chemistry of the PHB membranes by inducing hydrolysis of the ester bonds in the PHB backbone creating carboxylic surface functional groups, which increased the hydrophilicity of the PHB surfaces. Cytocompatibility studies showed increased proliferation of human osteoblasts (bone forming cells) on the NaOH treated PHB membranes compared to the untreated ones. Importantly, in vitro bacterial studies with Staphylococcus aureus (S. aureus) indicated that the NaOH-treated PHB surfaces inhibited S. aureus growth more than 60% after 48 hours of culture compared to the untreated PHB membrane. Thus, this study, for the first time, showed that nanofeatured PHB membranes modified with a NaOH treatment may be a useful anti-bacterial, osteoconductive GBR membrane for numerous orthopedic, cranio-maxillofacial and dental tissue engineering applications.
引导骨再生（GBR）在骨科、颅颌面和牙科组织工程应用中的原理是，为治疗大的骨缺损创造一个隔离空间，同时排除缺损区域纤维结缔组织的形成。在牙科手术中，GBR膜放置在拔牙后的牙槽窝内靠近牙种植体的位置，以便在种植部位长出新骨，同时抑制口腔菌群微生物引起的感染。聚（R）-3-羟基丁酸（PHB）是一种由多种微生物合成的天然聚酯，已被用于各种生物医学应用。在本研究中，为了提高PHB作为GBR的性能，设计了一种基于NaOH的碱性处理方法来制备具有纳米特征的PHB膜。对新制备的具有纳米特征的PHB膜进行了GBR应用研究。结果表明，一种快速、简单且廉价的氢氧化钠处理通过诱导PHB主链中酯键的水解，产生羧基表面官能团，从而改变了PHB膜的纳米结构表面形态和化学性质，增加了PHB表面的亲水性。细胞相容性研究表明，与未处理的PHB膜相比，在NaOH处理的PHB膜上人类成骨细胞（骨形成细胞）的增殖增加。重要的是，用金黄色葡萄球菌进行的体外细菌研究表明，与未处理的PHB膜相比，NaOH处理的PHB表面在培养48小时后对金黄色葡萄球菌生长的抑制率超过60%。因此，本研究首次表明，经NaOH处理改性的具有纳米特征的PHB膜可能是一种适用于众多骨科、颅颌面和牙科组织工程应用的有用的抗菌、骨传导性GBR膜。
