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Yan Gao,1 Xi Lin,1 Yadong Zhao,2 Shulan Xu,1 Chunhua Lai,1 Zehong Guo,1 Wangxi Wu,1 Xianglong Ding,1 Fang Jia,1 Lei Zhou,1 Ying Liu3 1Center of Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Inner Mongolia People’ Hospital, Huhhot, Inner Mongolia 010017, People’s Republic of China; 3Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of ChinaCorrespondence: Ying LiuDepartment of Endodontics, Stomatological Hospital, Southern Medical University, 366 South Jiang Nan Road, Hai Zhu District, Guangzhou 510280, People’s Republic of ChinaTel +86-20-84408890Fax +86-20-84433177Email 286668937@smu.edu.cnBackground: Improvements in the early osseointegration of titanium implants require investigations on the bone-implant interface, which is a critical and complex challenge. The surface cleanliness of titanium implants plays an important role at this interface. However, the implant surface would inevitably absorb contamination such as organic hydrocarbons, which is not conductive to the establishment of early osseointegration. Herein, an optimized approach for removing contamination from titanium surfaces was studied.Methods: The TiO2-B＠anatase NWs (nanowires) were prepared on titanium substrates through a hydrothermal process. A methylene blue degradation experiment was performed to assess the photodegradation activity. The cleaning effect of the photocatalysis of TiO2-B＠anatase NWs on a titanium surface and the cellular early response was determined by analyzing cell morphology, attachment, proliferation and differentiation.Results: The results indicated that the photocatalysis of TiO2-B＠anatase NWs could effectively remove hydrocarbons on titanium surfaces without sacrificing the favourable titanium surface morphology. The methylene blue degradation experiment revealed that the photocatalysis of TiO2-B＠anatase NWs had powerful degradation activity, which is attributed to the presence of strong oxidants such as ·OH. In addition, compared to the merely ultraviolet-treated titanium surfaces, the titanium surfaces treated after the NWs photocatalytic cleaning process markedly enhanced cellular early response.Conclusion: The photocatalysis of TiO2-B＠anatase NWs for the removal of contamination from titanium surfaces has the potential to enable the rapid and complete establishment of early osseointegration.Keywords: photocatalysis, nanowires, TiO2, titanium implant, osseointegration

Cong Chen,1,* Feng Jia,2,* Zhibo Hou,3 Shu Ruan,4 Qibin Lu1 1Department of Gynecology of Traditional Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, 3First Department of Respiratory Medicine, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, Jiangsu, China *These authors contributed equally to this work Abstract: Paeonol (Pae; 2'-hydroxy-4'-methoxyacetophenone) has attracted intense attention as a potential therapeutic agent against various cancers. However, the use of Pae is limited owing to its hydrophobicity. Recently, biodegradable polymeric nanoparticles with amphiphilic copolymers have been used as drug carriers; these have better bioavailability and are promising tumor-targeted drug delivery systems. In the current study, we prepared Pae-loaded nanoparticles (Pae-NPs) with amphiphilic block copolymers using nanoprecipitation. The physiochemical characteristics and antitumor effects of nanoparticles were evaluated in different cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed substantial inhibition of cell growth by Pae-NPs. Moreover, lower doses of Pae-NPs inhibited cell growth more efficiently than the equivalent doses of free Pae. Inhibition was characterized by significant elevation of intracellular reactive oxygen species and subsequent inhibition of Akt and regulation of apoptotic proteins, which could be partly reversed by pretreatment with the antioxidant N-acetylcysteine. In vivo results also demonstrated that Pae-NPs could exert much stronger antitumor effects than free Pae. Therefore, Pae-NPs represent a promising delivery system to overcome the low solubility of Pae and enable its use in treating cancer. Keywords: nanoparticles, drug delivery, paeonol

Huae Xu,1,* Feng Jia,2,* Pankaj Kumar Singh,3 Shu Ruan,4 Hao Zhang,5,* Xiaolin Li5 1Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, People’s Republic of China; 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, 5Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The anti-glioma effect of temozolomide (Tem) is sometimes undermined by the emerging resistance. Recently, resveratrol (Res), herbal medicine extracted from grape seeds, has been demonstrated for its potential use in chemosensitization. In the current study, both these drugs were loaded simultaneously into nanoparticles with methoxy poly(ethylene glycol)-poly epsilon caprolactone (mPEG-PCL) as drug carriers in order to achieve better antitumor efficiency. Tem/Res-coloaded mPEG-PCL nanoparticles were constructed, characterized, and tested for antitumor effect on glioma cells by using in vitro and xenograft model system. The nanoparticle constructs were satisfactory with drug loading content (Res =~12.4%; Tem =~9.3%) and encapsulation capacity of >85% for both the drugs. In addition, the coencapsulation led to better in vitro stability of the nanoparticles than Tem-loaded nanoparticles. An in vitro uptake study demonstrated a high uptake efficiency of the nanoparticles by glioma cells. The synergistic antitumor effect against glioma cells was observed in the combinational treatment of Res and Tem. Tem/Res-coloaded nanoparticles induced higher apoptosis in U87 glioma cells as compared to cells treated by the combination of free drugs. Tem/Res-coloaded particles caused more effective inhibition of phosphor-Akt, leading to upregulation of the downstream apoptotic proteins. In addition, the in vivo study showed the superior tumor delaying effect of coloaded nanoparticles than that of free drug combination. These results suggest that Tem/Res-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for glioma therapy. Keywords: resveratrol, temozolomide, synergy, mPEG-PCL, polymeric, drug delivery

Xianglong Ding,1 Lei Zhou,1 Jingxu Wang,2 Qingxia Zhao,3 Xi Lin,1 Yan Gao,1 Shaobing Li,4 Jingyi Wu,1 Mingdeng Rong,4 Zehong Guo,1 Chunhua Lai,1 Haibin Lu,4 Fang Jia11Center of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, 2Department of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, 3Department of Stomatology, Nanfang Hospital, 4Department of Periodontics and Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaAbstract: In the present work, a hierarchical hybrid micro/nanostructured titanium surface was obtained by sandblasting with large grit and acid etching (SLA), and nanotubes of different diameters (30 nm, 50 nm, and 80 nm) were superimposed by anodization. The effect of each SLA-treated surface decorated with nanotubes (SLA + 30 nm, SLA + 50 nm, and SLA + 80 nm) on osteogenesis was studied in vitro and in vivo. The human MG63 osteosarcoma cell line was used for cytocompatibility evaluation, which showed that cell adhesion and proliferation were dramatically enhanced on SLA + 30 nm. In comparison with cells grown on the other tested surfaces, those grown on SLA + 80 nm showed an enhanced expression of osteogenesis-related genes. Cell spread was also enhanced on SLA + 80 nm. A canine model was used for in vivo evaluation of bone bonding. Histological examination demonstrated that new bone was formed more rapidly on SLA-treated surfaces with nanotubes (especially SLA + 80 nm) than on those without nanotubes. All of these results indicate that SLA + 80 nm is favorable for promoting the activity of osteoblasts and early bone bonding.Keywords: nanotopography, osseointegration, dental and orthopedic implant, titanium

Background: Improvements in the early osseointegration of titanium implants require investigations on the bone-implant interface, which is a critical and complex challenge. The surface cleanliness of titanium implants plays an important role at this interface. However, the implant surface would inevitably absorb contamination such as organic hydrocarbons, which is not conductive to the establishment of early osseointegration. Herein, an optimized approach for removing contamination from titanium surfaces was studied., Methods: The TiO 2 -B＠anatase NWs (nanowires) were prepared on titanium substrates through a hydrothermal process. A methylene blue degradation experiment was performed to assess the photodegradation activity. The cleaning effect of the photocatalysis of TiO 2 -B＠anatase NWs on a titanium surface and the cellular early response was determined by analyzing cell morphology, attachment, proliferation and differentiation., Results: The results indicated that the photocatalysis of TiO 2 -B＠anatase NWs could effectively remove hydrocarbons on titanium surfaces without sacrificing the favourable titanium surface morphology. The methylene blue degradation experiment revealed that the photocatalysis of TiO 2 -B＠anatase NWs had powerful degradation activity, which is attributed to the presence of strong oxidants such as · OH. In addition, compared to the merely ultraviolet-treated titanium surfaces, the titanium surfaces treated after the NWs photocatalytic cleaning process markedly enhanced cellular early response., Conclusion: The photocatalysis of TiO 2 -B＠anatase NWs for the removal of contamination from titanium surfaces has the potential to enable the rapid and complete establishment of early osseointegration., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Gao et al.)