Suchergebnisse

Yue Song,1,* Kaifeng Lin,2,* Shu He,3,* Chunmei Wang,1 Shuaishuai Zhang,1 Donglin Li,1 Jimeng Wang,4 Tianqing Cao,1 Long Bi,1 Guoxian Pei1 1Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China; 2Second Department of Orthopedics and Traumatology, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, Fuzhou, China; 3Department of Orthopedics, Xi'an Hong Hui Hospital, Xi'an, China; 4Department of Orthopedics, The 251st Hospital of Chinese PLA, Zhangjiakou, China *These authors contributed equally to this work Background and aim: As a newly emerging three-dimensional (3D) printing technology, low-temperature robocasting can be used to fabricate geometrically complex ceramic scaffolds at low temperatures. Here, we aimed to fabricate 3D printed ceramic scaffolds composed of nano-biphasic calcium phosphate (BCP), polyvinyl alcohol (PVA), and platelet-rich fibrin (PRF) at a low temperature without the addition of toxic chemicals.Methods: Corresponding nonprinted scaffolds were prepared using a freeze-drying method. Compared with the nonprinted scaffolds, the printed scaffolds had specific shapes and well-connected internal structures.Results: The incorporation of PRF enabled both the sustained release of bioactive factors from the scaffolds and improved biocompatibility and biological activity toward bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. Additionally, the printed BCP/PVA/PRF scaffolds promoted significantly better BMSC adhesion, proliferation, and osteogenic differentiation in vitro than the printed BCP/PVA scaffolds. In vivo, the printed BCP/PVA/PRF scaffolds induced a greater extent of appropriate bone formation than the printed BCP/PVA scaffolds and nonprinted scaffolds in a critical-size segmental bone defect model in rabbits.Conclusion: These experiments indicate that low-temperature robocasting could potentially be used to fabricate 3D printed BCP/PVA/PRF scaffolds with desired shapes and internal structures and incorporated bioactive factors to enhance the repair of segmental bone defects. Keywords: three-dimensional printing, nano-biphasic calcium phosphate, polyvinyl alcohol, platelet-rich fibrin, bone substitutes, tissue engineering

Yun Gyeong Kang,1 Jie Wei,2 Ji Won Shin,1 Yan Ru Wu,3 Jiacan Su,4 Young Shik Park,5 Jung-Woog Shin1,3,6 1School of Biomedical Engineering, Inje University, Gimhae, Republic of Korea; 2Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China; 3Department of Health Science and Technology, Inje University, Gimhae, Republic of Korea; 4Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China; 5School of Biological Science, Inje University, Gimhae, Republic of Korea; 6Cardiovascular and Metabolic Disease Center/Institute of Aged Life Redesign/UHARC, Inje University, Gimhae, Republic of Korea Background: Successful bone tissue engineering using scaffolds is primarily dependent on the properties of the scaffold, including biocompatibility, highly interconnected porosity, and mechanical integrity. Methods: In this study, we propose new composite scaffolds consisting of mesoporous magnesium silicate (m_MS), polycaprolactone (PCL), and wheat protein (WP) manufactured by a rapid prototyping technique to provide a micro/macro porous structure. Experimental groups were set based on the component ratio: (1) WP0% (m_MS:PCL:WP =30:70:0 weight per weight; w/w); (2) WP15% (m_MS:PCL:WP =30:55:15 w/w); (3) WP30% (m_MS:PCL:WP =30:40:30 w/w). Results: Evaluation of the properties of fabricated scaffolds indicated that increasing the amount of WP improved the surface hydrophilicity and biodegradability of m_MS/PCL/WP composites, while reducing the mechanical strength. Moreover, experiments were performed to confirm the biocompatibility and osteogenic differentiation of human mesenchymal stem cells (MSCs) according to the component ratio of the scaffold. The results confirmed that the content of WP affects proliferation and osteogenic differentiation of MSCs. Based on the last day of the experiment, ie, the 14th day, the proliferation based on the amount of DNA was the best in the WP30% group, but all of the markers measured by PCR were the most expressed in the WP15% group. Conclusion: These results suggest that the m_MS/PCL/WP composite is a promising candidate for use as a scaffold in cell-based bone regeneration. Keywords: mesoporous magnesium silicate, wheat protein, scaffold, bone tissue engineering, osteogenic differentiation

Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 3Department of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 4Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 6Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People's Republic of China *These authors contributed equally to this work Purpose: Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods: Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results: Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of <0.1. The encapsulation efficacy of liposomal pemetrexed was 63.5%, which is rather high for water-soluble drugs in liposomes. The IC50 of liposomal pemetrexed following treatment with MDR breast cancer cells (MCF-7 cells overexpressing ABCC5) was 2.6-fold more effective than pemetrexed. The in vivo biodistribution study showed that the liposomes significantly accumulated in tumors 24 h after injection. The antitumor assay in mice bearing MDR breast cancer xenograft tumors confirmed the superior antitumor activity of liposomal pemetrexed over pemetrexed. It was also found that the improved therapeutic effect of liposomal pemetrexed may be attributed to apoptosis through both extrinsic and intrinsic pathways. Conclusion: Liposomal pemetrexed represents a potential therapeutic approach for overcoming breast cancer MDR. Keywords: cancer nanotechnology, breast cancer, multidrug resistance, pemetrexed, liposomes

Jun Ma,1,* Yunfei He,1,2,* Xilin Liu,1,* Weiming Chen,3 An Wang,1,4 Chia-Ying Lin,5,6 Xiumei Mo,3 Xiaojian Ye1 1Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 2Department of Spinal Surgery, Lanzhou General Hospital of Lanzhou Military Command Region, Lanzhou, 3College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 4Department of Orthopaedics, Shanghai Armed Police Force Hospital, Shanghai, China; 5Structural Tissue Evaluation and Engineering Laboratories, Department of Biomedical Engineering, 6Department of Orthopaedic Surgery, University of Cincinnati, Cincinnati, OH, USA *These authors contributed equally to this work Introduction: Herniation of the nucleus pulposus (NP) because of defects in the annulus fibrosus (AF) is a well-known cause of low back pain. Defects in the AF thus remain a surgical challenge, and efforts have been made to develop new techniques for closure and repair. In this study, we developed an electrospun aligned nanoyarn scaffold (AYS) and nanoyarn/three-dimensional porous nanofibrous hybrid scaffold (HS) for AF tissue engineering. Methods: The AYS was fabricated via conjugated electrospinning, while the aligned nanofibrous scaffold (AFS) was prepared by traditional electrospinning as a baseline scaffold. The HS was constructed by freeze-drying and cross-linking methods. Scanning electron microscopy and mechanical measurement were used to characterize the properties of these scaffolds. Bone marrow derived mesenchymal stem cells (BMSCs) were seeded on scaffolds, and cell proliferation was determined by CCK-8 assay, while cell infiltration and differentiation were assessed by histological measurement and quantitative real-time polymerase chain reaction, respectively.Results: Morphological measurements showed that AYS presented a relatively better three-dimensional structure with larger pore sizes, higher porosity, and better fibers' alignment compared to AFS. Mechanical testing demonstrated that the tensile property of AFS and AYS was qualitatively similar to the native AF tissue, albeit to a lesser extent. When BMSCs were seeded and cultured on these scaffolds, the number of cells cultured on HS and AYS was found to be significantly higher than that on AFS and culture plate after 7 days of culture (P0.05). BMSCs seeded on AYS demonstrated an increased expression of COL1A1, while the expression levels of SOX-9, COL2A1, and Aggrecan were higher in HS compared to other scaffolds (P<0.05). Conclusion: These findings indicate that HS makes a proper scaffold for the AF tissue engineering as it replicates the axial compression and tensile property of AF, thereby providing a better platform for cell infiltration and cell–scaffold interaction. Keywords: electrospinning, nanoyarn, three-dimensional scaffold, cell infiltration, annulus fibrosus, tissue engineering

Zhen Yang,1,* Juanli Duan,1,* Jianlin Wang,1,* Qi Liu,1 Runze Shang,1 Xisheng Yang,1 Peng Lu,2 Congcong Xia,1 Lin Wang,1 Kefeng Dou1 1Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China; 2Department of Hepatobiliary Surgery, Hainan Branch of Chinese PLA General Hospital, Sanya, People's Republic of China *These authors contributed equally to this work Introduction: A safe and effective in vivo siRNA delivery system is a prerequisite for liver tumor treatment based on siRNA cancer therapeutics. Nanoparticles based on superparamagnetic iron oxide (SPIO) provide a promising delivery system. In this study, we aimed to explore a novel nanoparticle, which is composed of SPIO.Materials and methods: The particles have a core of iron oxide that is modified by galactose (Gal) and polyethylenimine (PEI), which act as shells, providing targeted delivery of therapeutic siRNA to the liver cancer. Gal-PEI-SPIO nanoparticles were synthesized, and the characteristics of the Gal-PEI-SPIO encapsulated with siRNA were analyzed.Results: The particles remained nanoparticles and displayed negligible cytotoxicity when loaded with siRNA. In a serum stability assay, the Gal-PEI-SPIO nanoparticles could shield the siRNA from serum degradation and prolong the half-life of the siRNA in the system. Simultaneously, we found that the mixture could be efficiently taken up by Hepa1–6 cells in a flow cytometry assay. To study the anticancer effect, quantitative polymerase chain reaction and Western blotting were used to validate the silencing efficacy of the complexes in vitro. Subsequently, the nanoparticle mixtures were administered intravenously to tumor-bearing mice to explore the tissue distribution and the effect of the siRNA against cancer. We found that the nanoparticles could provide targeted siRNA delivery, accumulate easily in orthotopic tumors, enhance siRNA accumulation in the tumor tissues for 24 h and protect the siRNA from serum nuclease degradation in comparison with the control group. After these study procedures, the mice were sacrificed, and the tumors were removed to compare the tumor size and analyze the therapeutic effect on tumor growth. The tumor volume and the liver/body weight ratio were significantly reduced in the si-c-Met therapy groups. Additionally, the mRNA levels were also lower than those observed in the controls.Conclusion: Based on these results, we concluded that Gal-PEI-SPIO represents a promising and efficient platform for siRNA delivery in tumor therapy. Keywords: Gal-PEI-SPIO, hepatocellular carcinoma, c-Met, nanoparticle, siRNA

Xin Huang,1,* Chengqi Fan,2,* Huanhuan Zhu,1 Wenjun Le,1 Shaobin Cui,1 Xin Chen,3 Wei Li,4 Fulei Zhang,4 Yong Huang,4 Donglu Shi,1,5 Zheng Cui,1,6 Chengwei Shao,2 Bingdi Chen1 1The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China; 2Radiology Department of Changhai Hospital, The Second Military Medical University, Shanghai, China; 3Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Jilin, China; 4International Joint Cancer Institute, The Second Military Medical University, Shanghai, China; 5The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, OH, USA; 6Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Introduction: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results: Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion: Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. Keywords: pancreatic cancer, Glypican-1, fluorescence imaging, magnetic resonance imaging, Gd–Au NCs

Yong Huang,1,* Guiqin Song,1,* Xiaotong Chang,1 Zhenhui Wang,2 Xuejiao Zhang,1 Shuguang Han,3 Zhuobin Su,4 Hejie Yang,5 Dongdong Yang,6 Xiaojun Zhang7 1College of Lab Medicine, Hebei North University, Zhangjiakou, China; 2Department of Nuclear Medicine, People's Liberation Army No 251 Hospital, Zhangjiakou, China; 3Institute of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; 4The First Affiliated Hospital, Hebei North University, Zhangjiakou, China; 5State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, China; 6School of Physics and Optoelectronic Engineering, Ludong University, Yantai, China; 7Department of Physics, Fourth Military Medical University, Xi'an, China *These authors contributed equally to this work Background: Poor mechanical properties, undesirable fast dissolution rate, and lack of antibacterial activity limit the application of hydroxyapatite (HA) as an implant coating material. To overcome these limitations, a hybrid coating of Ag+-substituted fluorhydroxyapatite and titania nanotube (TNT) was prepared.Methods: The incorporation of silver into the HA-TiO2 hybrid coating improves its antimicrobial properties. The addition of F as a second binary element increases the structural stability of the coating. The TNT/F-and-Ag-substituted HA (FAgHA) bilayer coating on the Ti substrate was confirmed by X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS).Results: The results indicate that the FAgHA/TNT nanocomposite coating has a dense and uniform morphology with a nano-rod-like structure. The solubility measurement result shows that the substitution of F- ions into the AgHA structure has a positive effect on the dissolution resistance of HA. The adhesion strength of FAgHA/TNT has significantly increased because of the interlocking of the roughened surface with nano-rod-like particles that entered into the voids of the TiO2 nanotubes. Compared with that of the bare Ti, the corrosion current density of FAgHA/TNT-coated Ti substrate decreased from 3.71 to 0.18 µA, and its corrosion resistance increased by almost two orders of magnitude. Moreover, despite pure HA, the FAgHA killed all viable Staphylococcus aureus after 24 hours of incubation. Although the fabricated FAgHA/TNT coating is hydrophobic, it induced deposition of the typical spherical apatite when immersed in a simulated body fluid (SBF); the osteoblasts spread very well on the surface of the coating. In addition, in vitro cell culture tests demonstrated cell viability and alkaline phosphatase (ALP) similar to pure HA, which indicated good cytocompatibility. Interestingly, compared with bare Ti, FAgHA/TNT-coated Ti surface was innocent for cell vitality and even more beneficial for cell osteogenesis in vitro.Conclusion: Enhancing the osseointegration and preventing infection in implants, the FAgHA/TNT-coated Ti makes implants more successful. Keywords: titania nanotube, silver, fluorhydroxyapatite, bactericidal effects, osteoin­ductivity

Qing Zhou,1,* Li Zhang,2,* TieHong Yang,1 Hong Wu1 1Department of Pharmaceutical Analysis, School of Pharmacy, Air Force Military Medical University, Xi'an, People's Republic of China; 2State Key Laboratory of Military Stomatology, Air Force Military Medical University, Xi'an, People's Republic of China *These authors contributed equally to this work Abstract: Polymeric micelles (PMs) have been widely investigated as nanocarriers for drug delivery and cancer treatments due to their excellent physicochemical properties, drug loading and release capacities, facile preparation methods, biocompatibility, and tumor targetability. They can be easily engineered with various functional moieties to further improve their performance in terms of bioavailability, circulation time, tumor specificity, and anticancer activity. The stimuli-sensitive PMs capable of responding to various extra- and intracellular biological stimuli (eg, acidic pH, altered redox potential, and upregulated enzyme), as well as external artificial stimuli (eg, magnetic field, light, temperature, and ultrasound), are considered as "smart" nanocarriers for delivery of anticancer drugs and/or imaging agents for various therapeutic and diagnostic applications. In this article, the recent advances in the development of stimuli-responsive PMs for drug delivery, imaging, and cancer therapy are reviewed. The article covers the generalities of stimuli-responsive PMs with a focus on their major delivery strategies and newly emerging technologies/nanomaterials, discusses their drawbacks and limitations, and provides their future perspectives. Keywords: nanomedicine, polymeric micelles, stimuli-responsive, drug delivery, cancer therapy

Jin-Hong Yan,1,* Chun-Hui Wang,2,* Ke-Wen Li,1,3,* Qi Zhang,1 Min Yang,1 Wei-Long Di-Wu,1 Ming Yan,1 Yue Song,1 Jing-Jing Ba,4 Long Bi,1 Yi-Sheng Han1 1Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 2Department of Army Military Medical Frontier Medical Service Brigade, Urumqi Ethnic Cadre College, Urumqi, Xinjiang Uyghur, 3Department of Orthopedics, Qinghai University Affiliated Hospital, Xining, Qinghai, 4Shandong Weigao Orthopedic Mechanics Laboratory, Weihai, Shandong, China *These authors contributed equally to this work Background and objective: The modulus of carbon fiber-reinforced polyether ether ketone (CFR-PEEK), a composite containing layers of carbon fiber sheets, can be precisely controlled to match bone. However, CFR-PEEK is biologically inert and cannot promote bone apposition. The objective of this study was to investigate whether graphene modification could enhance the bioactivity of CFR-PEEK.Methods and results: In vitro, the proliferation and differentiation of rat bone marrow stromal cells on scaffolds were quantified via cell-counting kit-8 assay and Western blotting analysis of osteoblast-specific proteins. Graphene modification significantly promoted bone marrow stromal cell proliferation and accelerated induced differentiation into osteogenic lineages compared to cells seeded onto nongraphene-coated CFR-PEEK. An in vivo rabbit extraarticular graft-to-bone healing model was established. At 4, 8, and 12 weeks after surgery, microcomputed tomography analyses and histological observations revealed significantly better microstructural parameters and higher average mineral apposition rates for graphene-modified CFR-PEEK implants than CFR-PEEK implants (P<0.05). van Gieson staining indicated more new bone was formed around graphene-modified CFR-PEEK implants than CFR-PEEK implants.Conclusion: Graphene may have considerable potential to enhance the bioactivity and osseointegration of CFR-PEEK implants for clinical applications. Keywords: graphene, carbon fiber-reinforced polyether ether ketone, surface modification, bioactivity, osseointegration

Jingjing Fu,1,2,* Junwei Gao,2,* Linji Gong,3,4 Yuanyuan Ma,1 Haiwei Xu,5 Zhanjun Gu,3,4 Jingci Zhu,1 Xiaotang Fan2 1School of Nursing, Third Military Medical University, Chongqing 400038, China; 2Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; 4University of Chinese Academy of Sciences, Beijing 100049, China; 5Southwest Eye Hospital/Southwest Hospital, Third Military Medical University, Chongqing 400038, China *These authors contributed equally to this work Introduction: Silica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period.Materials and methods: Herein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults.Results: SiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment.Discussion: These findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood. Keywords: silica nanoparticles, nanotoxicity, hippocampal neurogenesis, neuroinflammation, social behavior

Nan Jiang,1–3 Lu Chen,1–3 Qianli Ma,4,5 Jianping Ruan1–3 1Department of Preventive Dentistry, College of Stomatology, Xi'an JiaoTong University, Xi'an, People's Republic of China; 2Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an JiaoTong University, Xi'an, People's Republic of China; 3Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an JiaoTong University, Xi'an, People's Republic of China; 4Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi'an, People's Republic of China; 5Department of Prosthodontics, College of Stomatology, Xi'an JiaoTong University, Xi'an, People's Republic of China Purpose: To investigate the amelogenesis-inductive effects of surface structures at the nanoscale. For this purpose, variable nanostructured titanium dioxide (TiO2) surfaces were used as a framework to regulate the amelogenic behaviors of ameloblasts with the administration of retinoic acid (RA)/dexamethasone (DEX). Materials and methods: TiO2 nanotubular (NT) surfaces were fabricated via anodization. Mouse ameloblast-like LS-8 cells were seeded and cultured on NT surfaces in the presence or absence of RA/DEX for 48 h. The amelogenic behaviors and extracellular matrix (ECM) mineralization of LS-8 cells on nanostructured Ti surfaces were characterized using field emission scanning electron microscope, laser scanning confocal microscope, quantitative polymerase chain reaction, MTT assay, and flow cytometry. Results: TiO2 NT surfaces (tube size ~30 and ~80 nm) were constructed via anodization at 5 or 20 V and denoted as NT5 and NT20, respectively. LS-8 cells exhibited significantly increased spread and proliferation, and lower rates of apoptosis and necrosis on NT surfaces. The amelogenic gene expression and ECM mineralization differed significantly on the NT20 and the NT5 and polished Ti sample surfaces in standard medium. The amelogenic behaviors of LS-8 cells were further changed by RA/DEX pretreatment, which directly drove maturation of LS-8 cells. Conclusion: Controlling the amelogenic behaviors of ameloblast-like LS-8 cells by manipulating the nanostructure of biomaterials surfaces represents an effective tool for the establishment of a systemic framework for supporting enamel regeneration. The administration of RA/DEX is an effective approach for driving the amelogenesis and maturation of ameloblasts. Keywords: TiO2 nanotube, LS-8, surface nanostructure, amelogenesis, retinoic acid