Department of Prosthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.
Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai 200011, China.
Colloids Surf B Biointerfaces. 2019 Apr 1;176:219-229. doi: 10.1016/j.colsurfb.2018.12.071. Epub 2019 Jan 3.
Guided bone regeneration (GBR) membranes have the potential to prevent the invasion of epithelial and connective tissues as well as to maintain a stable space for facilitating the ingrowth of regenerative bone tissue. However, the bioactivity and regeneration potential of currently available membranes still need to be improved. In this study, a novel bi-layered membrane with both osteogenic and antibacterial functions was developed for GBR applications. The loose layer (LL) of the membrane was composed of conjugated electrospun poly (lactic-co-glycolic acid) (PLGA)/gelatin nanofibers incorporating dexamethasone-loaded mesoporous silica nanoparticles (DEX@MSNs), while the dense layer (DL) of the membrane consisted of traditionally electrospun PLGA nanofibers loaded with the broad-spectrum antibiotic doxycycline hyclate (DCH). Morphological results showed that the LL (DEX@MSNs/PLGA/Gel) membrane exhibited a porous and loosely packed structure, which was beneficial for cell adhesion and infiltration, while the DL (DCH/PLGA) membrane remained dense enough to act as a barrier. In vitro drug release tests indicated that both DEX and DCH followed a favorable sustained release profile. The cell viability evaluation suggested that the electrospun membranes possessed good cytocompatibility. Furthermore, in vitro osteogenesis analyses demonstrated that the DEX@MSNs/PLGA/Gel composite membrane possessed an enhanced osteoinductive capacity for rat bone marrow stem cells (BMSCs), which was verified by the increased alkaline phosphatase (ALP) activity, the enhanced calcium deposition, and the upregulated osteocalcin (OCN) expression. In vitro antimicrobial experiments revealed the effective antibacterial potency of the DCH/PLGA membrane. In conclusion, the prepared nanocarrier-incorporated bi-layered composite membrane with combined osteogenic and antibacterial properties may be a promising candidate for GBR application.
引导骨再生（GBR）膜具有防止上皮和结缔组织侵入以及维持稳定空间以促进再生骨组织生长的潜力。然而，目前可用的膜的生物活性和再生潜力仍有待提高。在这项研究中，开发了一种具有成骨和抗菌功能的新型双层膜，用于 GBR 应用。膜的疏松层（LL）由负载地塞米松的介孔硅纳米粒子（DEX@MSNs）的共轭电纺聚（乳酸-共-乙醇酸）（PLGA）/明胶纳米纤维组成，而膜的致密层（DL）由传统电纺 PLGA 纳米纤维组成纤维负载广谱抗生素盐酸多西环素（DCH）。形态学结果表明，LL（DEX@MSNs/PLGA/Gel）膜呈现多孔和疏松的堆积结构，有利于细胞黏附和渗透，而 DL（DCH/PLGA）膜保持足够致密以充当屏障。体外药物释放试验表明，DEX 和 DCH 均遵循有利的持续释放曲线。细胞活力评估表明，电纺膜具有良好的细胞相容性。此外，体外成骨分析表明，DEX@MSNs/PLGA/Gel 复合膜对大鼠骨髓基质细胞（BMSCs）具有增强的成骨能力，这通过碱性磷酸酶（ALP）活性的增加、钙沉积的增强和骨钙素（OCN）表达的上调得到证实。体外抗菌实验揭示了 DCH/PLGA 膜的有效抗菌效力。总之，具有成骨和抗菌性能的纳米载体复合双层复合膜可能是 GBR 应用的有前途的候选物。
