Publications by authors named "Kaili Lin"

95 Publications

Protective Effect of Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway.

Front Pharmacol 2021 16;12:640297. Epub 2021 Apr 16.

Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Hong Kong Special Administrative Region (HKSAR), Kowloon Tong, China.

() a famous formula in traditional Chinese medicine, has been clinically used for centuries for treating cerebral diseases, but the protective effects of pre-treatment with on cerebral ischemia have not yet been reported. The present study aimed to test such protective effects and elucidate the underlying mechanisms on cerebral ischemia in rats by phenotypic approaches (i.e. including the neurological functional score, cerebral infarct area, neuron apoptosis, and brain oxidative stress status) and target-based approaches (i.e. involving the GSK-3β/HO-1 pathway). AGNHW was administered orally at the doses of 386.26, 772.52, and 1545.04 mg/kg respectively for 7 days to male Sprague-Dawley rats and then cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1.5 h. Pre-treatment with AGNHW significantly ameliorated ischemic damage to the brain in a dose-dependent manner, including reduction of the neurological deficit score and infarct area. AGNHW pre-treatment increased the number of Nissl cells, NeuN and DCX cells, and decreased the number of Tunel cells. Moreover, AGNHW reversed the up-regulation of ROS and MDA induced by cerebral ischemia. AGNHW pre-treatment increased the expression of p-GSK-3β(Ser9)/GSK-3β (glycogen synthase kinase-3β) ratio and heme oxygenase-1 (HO-1). These results firstly revealed that short-term pre-treatment of AGNHW could significantly protect the rats from injury caused by cerebral ischemia-reperfusion, which support further clinical studies for disease prevention. The protective effect of AGNWH pre-treatment could be associated with its antioxidant properties by the activation of GSK-3β-mediated HO-1 pathway.
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http://dx.doi.org/10.3389/fphar.2021.640297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085595PMC
April 2021

An overview of polyester/hydroxyapatite composites for bone tissue repairing.

J Orthop Translat 2021 May 1;28:118-130. Epub 2021 Apr 1.

Department of Oral & Cranio-Maxillofacial Surgery, 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.

Objectives: The polyester/hydroxyapatite (polyester/HA) composites play an important role in bone tissue repairing, mostly because they mimic the composition and structure of naturally mineralized bone tissue. This review aimed to discuss commonly used geometries of polyester/HA composites, including microspheres, membranes, scaffolds and bulks, and their applications in bone tissue repairing and to discuss existed restrictions and developing trends of polyester/HA.

Methods: The current review was conducted by searching Web of Science, and Google Scholar for relevant studies published related with polyester/HA composites. Selected studies were analyzed with a focus on the fabrication techniques, properties (mechanical properties, biodegradable properties and biological properties) and applications of polyester/HA composites in bone repairing.

Results: A total of 111 articles were introduced to discuss the review. Different geometries of polyester/HA composites were discussed. In addition, properties and applications of polyester/HA composites were evaluated. The addition of HA into polyester can adjust the mechanical and biodegradability of composites. Besides, the addition of HA into polyester can improve its osteogenic abilities. The results showed that polyester/HA composites can ideal candidate for bone tissue repairing.

Conclusion: Polyester/HA composites have many remarkable properties, such as appropriate mechanical strength, biodegradability, favorable biological properties. Diverse geometries of polyester/HA composites have been used in bone repairing, drug delivery and implant fixation. Further work needs to be done to investigate existed restrictions, including the controlled degradation rate, controlled drug release performance, well-matched mechanical properties, and novel fabrication techniques.

The Translational Potential Of This Article: The present review reveals the current state of the polyester/HA composites used in bone tissue repairing, contributing to future trends of polyester/HA composites in the forthcoming future.
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http://dx.doi.org/10.1016/j.jot.2021.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050106PMC
May 2021

20()-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis.

J Ginseng Res 2021 Mar 16;45(2):325-333. Epub 2020 Jul 16.

Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR), China.

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20()-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation . However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis.

Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus.

Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus.

Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.jgr.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020272PMC
March 2021

Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/Acvr2b competitive receptor-activated Smad pathway.

Biomaterials 2021 May 27;272:120718. Epub 2021 Mar 27.

Department of Oral & Cranio-Maxillofacial Surgery, 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, PR China; Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China. Electronic address:

Mesenchymal stem cell-derived exosomes (MSC-exos), with its inherent capacity to modulate cellular behavior, are emerging as a novel cell-free therapy for bone regeneration. Herein, focusing on practical applying problems, the osteoinductivity of MSC-exos produced by different stem cell sources (rBMSCs/rASCs) and culture conditions (osteoinductive/common) were systematically compared to screen out an optimized osteogenic exosome (BMSC-OI-exo). Via bioinformatic analyses by miRNA microarray and in vitro pathway verification by gene silencing and miRNA transfection, we first revealed that the osteoinductivity of BMSC-OI-exo was attributed to multi-component exosomal miRNAs (let-7a-5p, let-7c-5p, miR-328a-5p and miR-31a-5p). These miRNAs targeted Acvr2b/Acvr1 and regulated the competitive balance of Bmpr2/Acvr2b toward Bmpr-elicited Smad1/5/9 phosphorylation. On these bases, lyophilized delivery of BMSC-OI-exo on hierarchical mesoporous bioactive glass (MBG) scaffold was developed to realize bioactivity maintenance and sustained release by entrapment in the surface microporosity of the scaffold. In a rat cranial defect model, the loading of BMSC-OI-exo efficiently enhanced the bone forming capacity of the scaffold and induced rapid initiation of bone regeneration. This paper could provide empirical bases of MSC-exo-based therapy for bone regeneration and theoretical bases of MSC-exo-induced osteogenesis mechanism. The BMSC-OI-exo-loaded MBG scaffold developed here represented a promising bone repairing strategy for future clinical application.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120718DOI Listing
May 2021

Enhancement of osteoporotic bone regeneration by strontium-substituted 45S5 bioglass time-dependent modulation of autophagy and the Akt/mTOR signaling pathway.

J Mater Chem B 2021 Apr;9(16):3489-3501

Department of Oral and Cranio-Maxillofacial Science, 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.

Osteoporosis (OP) is a major systemic bone disease leading to an imbalance in bone homeostasis which remains a challenge in the current treatment of bone defects. Our previous studies on strontium (Sr) doping apparently stimulated osteogenesis of bioceramics, which suggested a promising strategy for the treatment of bone defects. However, the potential effects and the underlying mechanisms of Sr-doping on osteoporotic bone defects still remain unclear. Autophagy is a conventional self-degradation process of cells involved in bone homeostasis and regeneration under physiological and pathological conditions. Therefore, it is essential to design appropriate biomaterials and investigate the associated osteogenic mechanisms via autophagy. Based on this hypothesis, Sr-doped 45S5 bioglass (Sr/45S5) was fabricated, and ovariectomy bone marrow-derived mesenchymal stem cells (OVX-BMSCs) were applied as the in vitro cell culture model. First, the optimal Sr-doping concentration of 10 mol% was screened by cell proliferation, ALP staining, alizarin red S staining and the real-time PCR assay. Then, the results of western blot (WB) analysis showed that Sr-induced osteogenic differentiation of OVX-BMSCs was associated with time-dependent modulation of autophagy and related to the AKT/mTOR signaling pathway. Meanwhile, the autophagy in Sr-induced osteogenic differentiation of OVX-BMSCs was detected by WB, immunofluorescence staining and transmission electron microscopy. Furthermore, the effect of osteogenic differentiation of OVX-BMSCs has been significantly inhibited by the administration of autophagy inhibitors and the AKT/mTOR pathway inhibitors, respectively, in the early and late periods of osteogenic differentiation. Finally, the results of the model of femoral condyle defects in OVX-rats indicated that Sr10/45S5 granules remarkably enhanced bone regeneration which provided the evidences in vivo. Our research indicates that Sr-doping provides a promising strategy to promote osteogenic differentiation of OVX-BMSCs and bone regeneration in osteoporotic bone defects via early improvement of autophagy and late activation of the Akt/mTOR signaling pathway.
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http://dx.doi.org/10.1039/d0tb02991bDOI Listing
April 2021

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review.

Front Bioeng Biotechnol 2021 9;9:591796. Epub 2021 Feb 9.

School of Stomatology, Xuzhou Medical University, Xuzhou, China.

Implant-supported dentures are widely used in patients with defect or loss of dentition because these have higher chewing efficiency and do not damage the adjacent teeth compared with fixed or removable denture. An implant-supported denture carries the risk of failure in some systemic diseases, including osteoporosis, because of a non-ideal local microenvironment. Clinically common physical and chemical modifications are used to change the roughness of the implant surface to promote osseointegration, but they have limitations in promoting osteoinduction and inhibiting bone resorption. Recently, many researchers have focused on the study of bioactive modification of implants and have achieved promising results. Herein we have summarized the progress in bioactive modification strategy to promote osseointegration by regulating the local osteoporotic microenvironment.
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http://dx.doi.org/10.3389/fbioe.2021.591796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903335PMC
February 2021

The effects of alignment and diameter of electrospun fibers on the cellular behaviors and osteogenesis of BMSCs.

Mater Sci Eng C Mater Biol Appl 2021 Jan 10;120:111787. Epub 2020 Dec 10.

Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China. Electronic address:

Electrospun fiber scaffolds, due to their mimicry of bone extracellular matrix (ECM), have become an important biomaterial widely applied in bone tissue engineering in recent years. While topographic cues of electrospun membranes such as alignment and diameter played vital roles in determining cellular behaviors. Yet few researches about the effects of these two significant parameters on osteogenesis have been reported. Thus, the present work explored the influence of aligned and random poly (L-lactic acid) (PLLA) fiber matrices with diameters of nanoscale (0.6 μm) and microscale (1.2 μm), respectively, on cellular responses of bone marrow mesenchymal stem cells (BMSCs), such as cell adhesion, migration, proliferation and osteogenesis. Our results revealed that aligned nanofibers (AN) could affect cell morphology and promote the migration of BMSCs after 24 h of cell culturing. Besides, AN group was observed to possess excellent biocompatibility and have significantly improved cell growth comparing with random nanofibers. More importantly, in vitro osteogenesis researches including ALP and Alizarin Red S staining, qRT-PCR and immunofluorescence staining demonstrated that BMSCs culturing on AN group exhibited higher osteogenic induction proficiency than that on aligned microfibers (AM) and random fiber substrates (RN and RM). Accordingly, aligned nanofiber scaffolds have greater application potential in bone tissue engineering.
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http://dx.doi.org/10.1016/j.msec.2020.111787DOI Listing
January 2021

Challenges and strategies for endothelialization and long-term lumen patency of vascular grafts.

Bioact Mater 2021 Jun 5;6(6):1791-1809. Epub 2020 Dec 5.

Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter < 4 mm) vascular grafts have a high risk of thrombosis and intimal hyperplasia (IH), which makes long-term lumen patency challengeable. Endothelial cells (ECs) form the inner endothelium layer, and are crucial for anti-coagulation and thrombogenesis. Thus, promoting endothelialization in vascular graft remodeling takes top priority, which requires recruitment of endothelia progenitor cells (EPCs), migration, adhesion, proliferation and activation of EPCs and ECs. Chemotaxis aimed at ligands on EPC surface can be utilized for EPC homing, while nanofibrous structure, biocompatible surface and cell-capturing molecules on graft surface can be applied for cell adhesion. Moreover, cell orientation can be regulated by topography of scaffold, and cell bioactivity can be modulated by growth factors and therapeutic genes. Additionally, surface modification can also reduce thrombogenesis, and some drug release can inhibit IH. Considering the influence of macrophages on ECs and smooth muscle cells (SMCs), scaffolds loaded with drugs that can promote M2 polarization are alternative strategies. In conclusion, the advanced strategies for enhanced long-term lumen patency of vascular grafts are summarized in this review. Strategies for recruitment of EPCs, adhesion, proliferation and activation of EPCs and ECs, anti-thrombogenesis, anti-IH, and immunomodulation are discussed. Ideal vascular grafts with appropriate surface modification, loading and fabrication strategies are required in further studies.
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http://dx.doi.org/10.1016/j.bioactmat.2020.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721596PMC
June 2021

Investigation for GSK3β expression in diabetic osteoporosis and negative osteogenic effects of GSK3β on bone marrow mesenchymal stem cells under a high glucose microenvironment.

Biochem Biophys Res Commun 2021 01 13;534:727-733. Epub 2020 Nov 13.

Department of Oral & Cranio-Maxillofacial Surgery, 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. Electronic address:

Osteoporosis is a common skeletal complication of diabetes mellitus (DM). The mechanisms underlying the pathophysiology of diabetic osteoporosis are complex. Glycogen synthase kinase-3β (GSK-3β) is a widely expressed serine/threonine kinase and associated with both DM and bone metabolism, which arouse our concern. In this study, we established the diabetic mouse model by high-fat diet combined with streptozotocin injection. Decreased bone mass and reduced osteogenesis were observed in femurs of the mice. Besides, we identified that there is an activated expression of GSK3β in the bone marrow mesenchymal stem cells (BMSCs) of diabetic mice. To explore the link between GSK3β and diabetic osteoporosis, we exposed BMSCs to a high glucose microenvironment in vitro and discovered that the glucose-induced GSK3β activation has negative osteogenic effects on BMSCs by suppressing β-catenin/Tcf7/Ccn4 signaling axis. Inhibition of GSK3β by specific concentrations of LiCl could reverse the impaired osteogenesis of BMSCs and increase expression of β-catenin, Tcf7 and Ccn4. Our research indicated that abnormal activation of GSK3β plays a role in diabetic osteoporosis and might be a potential target to treat diabetic osteoporosis.
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http://dx.doi.org/10.1016/j.bbrc.2020.11.010DOI Listing
January 2021

Bone marrow stromal cells stimulated by strontium-substituted calcium silicate ceramics: release of exosomal miR-146a regulates osteogenesis and angiogenesis.

Acta Biomater 2021 01 28;119:444-457. Epub 2020 Oct 28.

Department of Orthodontics, Shanghai Ninth People's Hospital, Collage of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China. Electronic address:

Dual-functional regulation for angiogenesis and osteogenesis is crucial for desired bone regeneration especially in large-sized bone defects. Exosomes have been demonstrated to facilitate bone regeneration through enhanced osteogenesis and angiogenesis. Moreover, functional stimulation to mesenchymal stromal cells (MSCs) was reported to further boost the pro-angiogenic ability of exosomes secreted. However, whether the stimulation by bioactive trace elements of biomaterials could enhance pro-angiogenic capability of bone marrow stromal cells (BMSCs)-derived exosomes and consequently promote in vivo vascularized bone regeneration has not been investigated. In this study, strontium-substituted calcium silicate (Sr-CS) was chosen and the biological function of BMSCs-derived exosomes after Sr-CS stimulation (Sr-CS-Exo) was systemically investigated. The results showed that Sr-CS-Exo could significantly promote in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs), which might be attributed to elevated pro-angiogenic miR-146a cargos and inhibition of Smad4 and NF2 proteins. Moreover, the in vivo study confirmed that Sr-CS-Exo possessed superior pro-angiogenic ability, which contributed to the accelerated developmental vascularization in zebrafish along with the neovascularization and bone regeneration in rat distal femur defects. Our findings may provide new insights into the mechanisms underlying Sr-containing biomaterials-induced angiogenesis, and for the first time, proposed that Sr-CS-Exo may serve as the candidate engineered-exosomes with dual-functional regulation for angiogenesis and osteogenesis in vascularized bone regeneration.
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http://dx.doi.org/10.1016/j.actbio.2020.10.038DOI Listing
January 2021

Advances of nanomaterial applications in oral and maxillofacial tissue regeneration and disease treatment.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020 Oct 8:e1669. Epub 2020 Oct 8.

Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Using bioactive nanomaterials in clinical treatment has been widely aroused. Nanomaterials provide substantial improvements in the prevention and treatment of oral and maxillofacial diseases. This review aims to discuss new progresses in nanomaterials applied to oral and maxillofacial tissue regeneration and disease treatment, focusing on the use of nanomaterials in improving the quality of oral and maxillofacial healthcare, and discuss the perspectives of research in this arena. Details are provided on the tissue regeneration, wound healing, angiogenesis, remineralization, antitumor, and antibacterial regulation properties of nanomaterials including polymers, micelles, dendrimers, liposomes, nanocapsules, nanoparticles and nanostructured scaffolds, etc. Clinical applications of nanomaterials as nanocomposites, dental implants, mouthwashes, biomimetic dental materials, and factors that may interact with nanomaterials behaviors and bioactivities in oral cavity are addressed as well. In the last section, the clinical safety concerns of their usage as dental materials are updated, and the key knowledge gaps for future research with some recommendation are discussed. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.
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http://dx.doi.org/10.1002/wnan.1669DOI Listing
October 2020

Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M.

Bioact Mater 2021 Mar 30;6(3):810-822. Epub 2020 Sep 30.

Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This study further demonstrated that CS bioceramics could stimulate osteogenesis better than β-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the osteogenesis capability of bone substitute materials.
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http://dx.doi.org/10.1016/j.bioactmat.2020.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528055PMC
March 2021

Laboratory biosafety emergency management for SARS-CoV-2.

J Biosaf Biosecur 2020 Dec 19;2(2):99-101. Epub 2020 Sep 19.

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China.

A biosafety laboratory is a prerequisite for studying emerging infectious diseases. Safe and effective operation in laboratories and the handling of pathogens determine the safety of the personnel, pathogens, and the environment in the laboratory, which are among the key factors for successful experimentation. In this article, we aimed to provide ideas for the emergency management of biosafety laboratories, including a discussion on the urgency of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related experimental activities, tracking clinical information, taking emergency measures, revision of the risk assessment process, and standardization of personal protective equipment and personnel behavior standards.
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http://dx.doi.org/10.1016/j.jobb.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501877PMC
December 2020

ZnO Nanomaterials: Current Advancements in Antibacterial Mechanisms and Applications.

Front Chem 2020 21;8:580. Epub 2020 Jul 21.

Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The prevalence of various diseases caused by bacteria has been increasing, and some traditional antibiotics have been reported to have varying degrees of resistance. ZnO nanomaterials (ZnO-NMs), due to their excellent broad-spectrum antibacterial properties, lasting antibacterial effects, and excellent biocompatibility, have quickly become the research focus of new antibacterial agents. While the narrow light response range of ZnO-NMs has limited the antibacterial performance to some extent and modifying it by various means to improve its response under visible light, such as doping metal/non-metal atoms, depositing noble metals and coupling carbon materials, which is a new research hotspot. Herein, the current mainstream claims about the antibacterial mechanisms and applications of ZnO-NMs are reviewed.
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http://dx.doi.org/10.3389/fchem.2020.00580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385224PMC
July 2020

Gaseous sulfur trioxide induced controllable sulfonation promoting biomineralization and osseointegration of polyetheretherketone implants.

Bioact Mater 2020 Dec 4;5(4):1004-1017. Epub 2020 Jul 4.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.

Fabricating a desired porous structure on the surface of biomedical polyetheretherketone (PEEK) implants for enhancing biological functions is crucial and difficult due to its inherent chemical inertness. In this study, a porous surface of PEEK implants was fabricated by controllable sulfonation using gaseous sulfur trioxide (SO) for different time (5, 15, 30, 60 and 90 min). Micro-topological structure was generated on the surface of sulfonated PEEK implants preserving original mechanical properties. The protein absorption capacity and apatite forming ability was thus improved by the morphological and elemental change with higher degree of sulfonation. In combination of the appropriate micromorphology and bioactive sulfonate components, the cell adhesion, migration, proliferation and extracellular matrix secretion were obviously enhanced by the SPEEK-15 samples which were sulfonated for 15 min. Finding from this study revealed that controllable sulfonation by gaseous SO would be an extraordinarily strategy for improving osseointegration of PEEK implants by adjusting the microstructure and chemical composition while maintaining excellent mechanical properties.
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http://dx.doi.org/10.1016/j.bioactmat.2020.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339002PMC
December 2020

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice.

J Infect Dis 2020 07;222(4):551-555

NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.
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http://dx.doi.org/10.1093/infdis/jiaa281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313959PMC
July 2020

20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3β in the Wnt/GSK-3β/β-catenin pathway.

J Ginseng Res 2020 May 25;44(3):475-482. Epub 2019 Mar 25.

Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR), China.

Background: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) . 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood.

Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection.

Results: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD.

Conclusion: PPD promotes NSC proliferation and neural differentiation via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.jgr.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195587PMC
May 2020

Nanoparticles modified by polydopamine: Working as "drug" carriers.

Bioact Mater 2020 Sep 18;5(3):522-541. Epub 2020 Apr 18.

Department of Oral & Cranio-Maxillofacial Surgery, 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, PR China.

Inspired by the mechanism of mussel adhesion, polydopamine (PDA), a versatile polymer for surface modification has been discovered. Owing to its unique properties like extraordinary adhesiveness, excellent biocompatibility, mild synthesis requirements, as well as distinctive drug loading approach, strong photothermal conversion capacity and reactive oxygen species (ROS) scavenging facility, various PDA-modified nanoparticles have been desired as drug carriers. These nanoparticles with diverse nanostructures are exploited in multifunctions, consisting of targeting, imaging, chemical treatment (CT), photodynamic therapy (PDT), photothermal therapy (PTT), tissue regeneration ability, therefore have attracted great attentions in plenty biomedical applications. Herein, recent progress of PDA-modified nanoparticle drug carriers in cancer therapy, antibiosis, prevention of inflammation, theranostics, vaccine delivery and adjuvant, tissue repair and implant materials are reviewed, including preparation of PDA-modified nanoparticle drug carriers with various nanostructures and their drug loading strategies, basic roles of PDA surface modification, etc. The advantages of PDA modification in overcoming the existing limitations of cancer therapy, antibiosis, tissue repair and the developing trends in the future of PDA-modified nanoparticle drug carriers are also discussed.
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http://dx.doi.org/10.1016/j.bioactmat.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170807PMC
September 2020

Amorphous carbon modification on implant surface: a general strategy to enhance osteogenic differentiation for diverse biomaterials via FAK/ERK1/2 signaling pathways.

J Mater Chem B 2019 04 19;7(15):2518-2533. Epub 2019 Mar 19.

Department of Oral and Cranio-Maxillofacial Science, 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.

Bone implants play a crucial role in bone repairing. Nevertheless, low capability of osteoinductivity and osteogenic differentiation for bone regeneration are disadvantages of bone implants. Therefore, it is imperative to develop a general and facile technology to promote the bioactivity of existing implants. Herein, a facile amorphous carbon-coating approach was developed to stimulate osteogenesis on diverse biomaterials, including bioceramics, biometals, and biopolymers via magnetron sputtering deposition. The results confirmed that the amorphous carbon-coating-modified surfaces could significantly enhance osteogenesis of bone marrow mesenchymal stem cells (BMSCs) on every kind of biomaterial surface. Furthermore, it was demonstrated that the FAK/ERK1/2 signaling pathways were involved in the osteogenic effects of this amorphous carbon coating. The bone regeneration ability using the calvarial bone defect model of rats confirmed that the amorphous carbon coating induced faster bone formation and mineralization, which suggested the effect of amorphous carbon coating on stimulating osteogenesis in vivo. These results suggest that the approach involving modifying a surface with amorphous carbon provides a general and simple strategy to enhance the osteogenesis for diverse biomaterials, and this has promising potential for bone repairing applications.
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http://dx.doi.org/10.1039/c8tb02850hDOI Listing
April 2019

The synergistic promotion of osseointegration by nanostructure design and silicon substitution of hydroxyapatite coatings in a diabetic model.

J Mater Chem B 2020 04;8(14):2754-2767

Department of Orthodontics, Shanghai Ninth People's Hospital, Collage of Stomatology, Shanghai Jiao Tong University School of Medicine, Innovative Research Team of High-level Local Universities in Shanghai, Shanghai 200011, China. and National Clinical Research Center for Oral Diseases, Shanghai 200011, China. and Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.

Accumulating evidence indicates much higher failure rates for biomedical titanium implants in diabetic patients. This phenomenon is attributed to impaired osteoblastic function, suppressed angiogenesis capacity, and abnormal osteoclast activation in diabetic patients. Our previous study demonstrated that titanium implants coated with highly crystalline nanostructured hydroxyapatite (nHA) promoted the osteogenic differentiation of bone marrow stromal cells (BMSCs) and bone-implant osseointegration under healthy conditions. Furthermore, recent studies showed that silicon-substituted biomaterials exhibited excellent osteogenesis and angiogenesis performance while repressing osteoclastogenesis. Hence, we proposed that a combination of nanostructural modification and Si substitution might produce synergetic effects to mitigate the impaired osseointegration of bone implants under diabetes mellitus (DM) conditions. To confirm this hypothesis, titanium implants coated with highly crystalline Si-substituted nHA (Si-nHA) were successfully fabricated via atmospheric plasma spraying combined with hydrothermal treatment. An in vitro study demonstrated that compared to the original HA coating, the nHA coating improved osteogenic and angiogenic differentiation and altered the OPG/RANKL ratio of DM-BMSCs. In addition, the Si-nHA coating further enhanced cell proliferation, improved osteogenic and angiogenic differentiation, and repressed osteoclastogenesis in DM-BMSCs. An in vivo study confirmed that the titanium implants coated with nHA or Si-nHA effectively promoted bone formation and bone-implant osseointegration in a diabetic rabbit model, with the Si-nHA coating exhibiting the best stimulatory effect. Collectively, the results suggest that the nanostructured topography and Si substitution act synergistically to ameliorate the poor bone regeneration and osseointegration associated with DM. Thus, the results provide a promising coating method for dental and orthopedic applications under diabetic conditions.
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http://dx.doi.org/10.1039/c9tb02882jDOI Listing
April 2020

A comparative study of the osteogenic performance between the hierarchical micro/submicro-textured 3D-printed Ti6Al4V surface and the SLA surface.

Bioact Mater 2020 Mar 9;5(1):9-16. Epub 2020 Jan 9.

Department of Oral & Cranio-Maxillofacial Surgery, 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.

Three-dimensional (3D) printed titanium and its alloys have broad application prospect in the field of biomedical implant materials, although the biological performance of the original surface should be improved. Learning from the development experience of conventional titanium implants, to construct a hierarchical hybrid topological surface is the future direction of efforts. Since the original 3D-printed (3D hereafter) Ti6Al4V surface inherently has micron-scale features, in the present study, we introduced submicron-scale pits on the original surface by acid etching to obtain a hierarchical micro/submicro-textured surface. The characteristic and biological performance of the 3D-printed and acid-etched (3DA hereafter) surface were evaluated and compared with the conventional sandblasted, large-grit, acid-etched (SLA hereafter) surface. Our results suggested the adhesion, proliferation and osteogenic differentiation of bone marrow derived mesenchymal stromal cells (BMSCs), as well as the osseointegration on 3DA surfaces were significantly improved. However, the overall osteogenic performance of the 3DA surface was not as good as the conventional SLA surface.
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http://dx.doi.org/10.1016/j.bioactmat.2019.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956677PMC
March 2020

Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats.

Adv Sci (Weinh) 2019 Dec 30;6(24):1901822. Epub 2019 Sep 30.

Department of Biology Hong Kong Baptist University (HKBU) Kowloon Tong Kowloon Hong Kong SAR China.

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN-like structures (mini-SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self-organization of mini-SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self-organization of the mini-SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini-SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self-organization of region-specific and functional brain-like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD.
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http://dx.doi.org/10.1002/advs.201901822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918115PMC
December 2019

A novel multifunctional carbon aerogel-coated platform for osteosarcoma therapy and enhanced bone regeneration.

J Mater Chem B 2020 01;8(3):368-379

School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.

Nowadays, groundbreaking strategies are urgently needed to address drug resistance, osteolysis, bone defects and other predicaments impeding the therapeutic efficacy of osteosarcoma. Among them, photothermal therapy (PTT), using systematically administrated nanoagents, exhibits attractive therapeutic efficacy, yet is powerless in bone defect regeneration. Herein, a novel multifunctional beta-tricalcium phosphate (β-Ca3(PO4)2, β-TCP) bioceramic platform-coated with carbon aerogel (CA), which was initially developed for tumor therapy, was fabricated. On account of the desirable photothermal capabilities of CA, sufficient hyperthermia is generated under the irradiation of an 808 nm laser to achieve a thorough ablation of osteosarcoma tumors. Furthermore, CA-coated surfaces provide extra roughness and a higher specific surface area, which promoted the protein recruitment ability and osteogenesis via a fibronectin (FN)-mediated signaling pathway. The photothermal therapeutic efficacy and osteogenesis capability of CA-coated β-TCP-C suggests a novel approach for the treatment of osteosarcoma and provides provoking inspiration for the prospective bio-application of CA.
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http://dx.doi.org/10.1039/c9tb02383fDOI Listing
January 2020

Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages.

Free Radic Biol Med 2019 12 21;145:146-160. Epub 2019 Sep 21.

Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. Electronic address:

Osteoarthritis (OA) is a progressive joint disorder that is primarily characterized by the degeneration and destruction of the articular cartilage. Cartilage matrix degradation, production of proinflammatory mediators, chondrocyte apoptosis and activation of macrophages in the synovial are involved in OA pathogenesis. Current non-surgical therapies for OA mainly aim at relieving pain but can barely alleviate the progression of OA. Quercetin, a naturally occurring flavonoid has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we explored the protective effects of quercetin on repairing OA-induced cartilage injuries and its possible mechanisms. In vitro, quercetin remarkably suppressed the expression of matrix degrading proteases and inflammatory mediators, meantime promoted the production of cartilage anabolic factors in interleukin-1β-induced (IL-1β) rat chondrocytes. In addition, quercetin exhibited anti-apoptotic effects by decreasing intracellular reactive oxygen species (ROS), restoring mitochondrial membrane potential (MMP) and inhibiting the Caspase-3 pathway in apoptotic rat chondrocytes. Moreover, quercetin induced M2 polarization of macrophages and upregulated the expression of transforming growth factor β (TGF-β) and insulin-like growth factor (IGF), which in turn created a pro-chondrogenic microenvironment for chondrocytes and promoted the synthesis of glycosaminoglycan (GAG) in chondrocytes. In vivo, intra-articular injection of quercetin alleviated the degradation of the cartilage and the apoptosis of chondrocytes in a rat OA model. Moreover, the expression of TGF-β1 and TGF-β2 in the synovial fluid and the ratio of M2 macrophages in the synovial membrane were elevated. In summary, our study proves that quercetin exerts chondroprotective effects by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages and creating a pro-chondrogenic environment for chondrocytes to enhance cartilage repair under OA environment. It is suggested that quercetin may serve as a potential drug for OA treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2019.09.024DOI Listing
December 2019

Roles of Glutamate Receptors in Parkinson's Disease.

Int J Mol Sci 2019 Sep 6;20(18). Epub 2019 Sep 6.

Department of Biology, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR 999077, China.

Parkinson's disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson's disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson's disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson's disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.
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http://dx.doi.org/10.3390/ijms20184391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769661PMC
September 2019

Immunotoxic Potential of Bisphenol F Mediated through Lipid Signaling Pathways on Macrophages.

Environ Sci Technol 2019 Oct 16;53(19):11420-11428. Epub 2019 Sep 16.

Shenzhen Center for Disease Control and Prevention , Shenzhen 518055 , China.

As a bisphenol A (BPA) alternative, bisphenol F (BPF) has been detected in various products, such as paper products, personal care products, and food. More importantly, the toxicity of BPF remains underexplored. We reported an integrated method to study the immunotoxic potentials and the underlying mechanisms of BPF on cell apoptosis, macrophage polarization, reactive oxygen species generation, expression and secretion of immune-related cytokines, and reprogramming of lipid signaling. More serious to BPA, BPF induced apoptosis in macrophages. The apoptosis was induced by activating both sphingomyelin-ceramide signaling pathway and oxidative stress, which included intrinsic (bax and caspase-9) and extrinsic apoptotic pathways (tumor necrosis factor receptor 1, caspase-8, and caspase-3). BPF exposure also induced the proinflammatory phenotype of the macrophage. This alternation was shown to be closely correlated with the modulation of biosynthesis and degradation of glycerophospholipids. This study demonstrated novel evidence that BPF as a substituent of BPA induced immunotoxic effects at environmentally relevant concentrations. We also showed that the reprogramming of lipidome plays a key role in the regulation of macrophage polarization and the induction of immunotoxicity of the BPA analogue.
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http://dx.doi.org/10.1021/acs.est.8b07314DOI Listing
October 2019

Advance of Nano-Composite Electrospun Fibers in Periodontal Regeneration.

Front Chem 2019 10;7:495. Epub 2019 Jul 10.

Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Periodontitis is considered to be the main cause of tooth loss, which affects about 15% of the adult population around the world. Scaling and root-planning are the conventional treatments utilized to remove the contaminated tissue and bacteria, but eventually lead to the formation of a poor connection-long junctional epithelium. Therefore, regenerative therapies, such as guided tissue/bone regeneration (GTR/GBR) for periodontal regeneration have been attempted. GTR membranes, acting as scaffolds, create three-dimensional (3D) environment for the guiding of cell attachment, proliferation and differentiation, and play a significant role in periodontal regeneration. Nano-composite scaffolds based on electrospun nanofibers have gained great attention due to their ability to emulate natural extracellular matrix (ECM) that affects cell survival, attachment and reorganization. Promoted protein absorption, cellular reactions, activation of specific gene expression and intracellular signaling, and high surface area to volume ratio are also important properties of nanofibrous scaffolds. Moreover, several bioactive components, such as bioceramics and functional polymers can be easily blended into nanofibrous matrixes to regulate the physical-chemical-biological properties and regeneration abilities. Simultaneously, functional growth factors, proteins and drugs are also incorporated to regulate cellular reactions and even modify the local inflammatory microenvironment, which benefit periodontal regeneration and functional restoration. Herein, the progress of nano-composite electrospun fibers for periodontal regeneration is reviewed, including fabrication methods, compound types and processes, and surface modifications, etc. Significant proof-of-concept examples are utilized to illustrate the results of material characteristics, cellular interactions and periodontal regenerations. Finally, the existing limitations of nano-composite electrospun fibers and the development tendencies in future are also discussed.
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http://dx.doi.org/10.3389/fchem.2019.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636673PMC
July 2019

Strontium released bi-lineage scaffolds with immunomodulatory properties induce a pro-regenerative environment for osteochondral regeneration.

Mater Sci Eng C Mater Biol Appl 2019 Oct 30;103:109833. Epub 2019 May 30.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. Electronic address:

The different lineage-specific biological properties of articular cartilage and subchondral bone present a great challenge in the construction of bi-lineage scaffolds for simultaneous osteochondral regeneration. To overcome this challenge, strontium incorporated calcium silicate (Sr-CS) ceramic was prepared for bi-lineage formation of scaffolds in this study. The positive result of Sr-CS in the regeneration of osteochondral defects was first proven by its improved effect on the osteogenesis and chondrogenesis induction of mesenchymal stem cells (MSCs). After that, scaffold-mediated macrophage polarization between classically activated inflammatory macrophages (termed M1Ф) and alternatively activated inflammatory macrophages (termed M2Ф) was assayed to investigate whether the incorporation of Sr into calcium silicate could alter host-to-scaffold immune response. Furthermore, the interactions between Sr-CS pretreated macrophages and MSCs differentiation were performed to prove the enhancement effect of suppressed inflammatory response on osteogenesis and chondrogenesis. In vivo transplantation showed that the Sr-CS scaffolds distinctly improved the regeneration of cartilage and subchondral bone, as compared to the calcium silicate scaffolds. On the one hand, the mechanism attributes to enhancement of strontium on the osteogenic and chondrogenic differentiation of MSCs. On the other hand, the reason can partially be attributed to suppressed synovial inflammatory response, which has improved effects on enhancement of osteogenesis and chondrogenesis. These findings suggest that monophasic Sr-CS scaffolds with a bi-lineage conducive property and an inflammatory response regulatory property represents a viable strategy for simultaneous regeneration of osteochondral defects.
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http://dx.doi.org/10.1016/j.msec.2019.109833DOI Listing
October 2019

Nano-Structure Designing Promotion Osseointegration of Hydroxyapatite Coated Ti-6Al-4V Alloy Implants in Diabetic Model.

J Biomed Nanotechnol 2019 Aug;15(8):1701-1713

Mammalian diabetes mellitus which contains altered microenvironment always impairs diverse cellular processes such as osteogenesis, angiogenesis and tissue regeneration via different mechanisms. For researches in materials science, modifying the ability of osteogenesis and angiogenesis in dental implants shows its significant importance. Nano-structure designing is considered as a facile strategy to improve the surface bioactivity of the implants. In this study, the nanorod-structured hydroxyapatite (HA) coatings on Ti-6Al-4V implants were facilely designed by the combination of plasma-spraying and hydrothermal treatment via varying reaction media. Intriguingly, hydrothermal treatment eliminated the glassy phase and impurity phases of HA coatings, and nanorod-structured surface was successfully constructed under hydrothermal treatment in Na₃PO₄ solution. Additionally, the HA coatings with nanorod-structured surface effectively promoted the adhesion and proliferation and further enhanced osteogenic differentiation of DM-rBMSCs . Moreover, the osseointegration of Ti-6Al-4V implants with nanorod-structured HA coating was also enhanced in diabetes mellitus rabbit model . Therefore, the nano-structured surface modification of HA coating on Ti-6Al-4V implants could target pathological bone loss via strengthening osteogenesis and angiogenesis and further potentially used as a therapeutic coating to promote diabetic osteointegration.
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http://dx.doi.org/10.1166/jbn.2019.2812DOI Listing
August 2019

Mussel-Inspired Polydopamine Coating: A General Strategy To Enhance Osteogenic Differentiation and Osseointegration for Diverse Implants.

ACS Appl Mater Interfaces 2019 Feb 8;11(7):7615-7625. Epub 2019 Feb 8.

School and Hospital of Stomatology and Shanghai Engineering Research Center of Tooth Restoration and Regeneration , Tongji University , Shanghai 200072 , China.

Surface modifications play an important role in endowing implant surface with excellent biocompatibility and bioactivity. Among the bioinspired surface modifications, the mussel-inspired polydopamine (PDA) has aroused great interest of researchers. Herein, we fabricated PDA on diverse implant surfaces, including biopolymer, biometal, and bioceramic. Then the effects of PDA coating on cell responsive behaviors in vitro and bone formation capacity in vivo were evaluated in detail. The results showed that PDA coating was fabricated on diverse samples surface successfully, which could significantly improve the hydrophilicity of different material surfaces. Furthermore, the results indicated that PDA coating exerted direct enhancing on the adhesion, proliferation and osteogenic differentiation of bone marrow derived mesenchymal stromal cells (BMSCs) through FAK and p38 signaling pathways. During the process, the focal adhesion protein expression and osteogenic-related genes expression level (e.g., ALP, BMP2, BSP, and OPN) were considerably upregulated. Most importantly, the in vivo study confirmed that PDA coating remarkably accelerated new bone formation and enhanced osseointegration performance. Our study uncovered the biological responses stimulated by PDA coating to make a better understanding of cell/tissue-PDA interactions and affirmed that PDA, a bioinspired polymer, has great potential as a candidate and functional bioactive coating medium in bone regeneration and orthopedic application.
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http://dx.doi.org/10.1021/acsami.8b21558DOI Listing
February 2019