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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research institute Neuroscience and Mental Health ProgramTorontoONCanada institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Long-term observation of the mineral trioxide aggregate extrusion into the periapical lesion:a case series

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International Journal of Oral Science 2013年第1期5卷 54-57页

作者： Seok-Woo Chang Tae-Seok Oh WooCheol Lee Gary Shun-Pan Cheung Hyeon-Cheol Kim Department of Conservative dentistry School of DentistryKyung Hee University Department of Conservative dentistry The Institute of Oral Health ScienceSamsung Medical CenterSungkyunkwan University School of Medicine Department of Conservative dentistry School of DentistryDental Research InstituteSeoul National University Area of Endodontics Faculty of Dentistrythe University of Hong Kong Department of Conservative dentistry School of DentistryPusan National UniversityDental Research Institute

One-step apexification using mineral trioxide aggregate(MTA) has been reported as an alternative treatment modality with more benefits than the use of long-term calcium hydroxide for teeth with open ***,orthograde placement of MTA is a challenging procedure in terms of length *** case series describes the sequence of events following apical extrusion of MTA into the periapical area during a one-step apexification procedure for maxillary central incisor with an infected immature *** long-term observation revealed complete resolution of the periapical radiolucent lesion around the extruded *** cases revealed that direct contact with MTA had no negative effects on healing of the periapical ***,intentional MTA overfilling into the periapical lesion is not to be recommended.

关键词： extrusion immature apex mineral trioxide aggregate one-step apexification open apex periapical healing

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Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

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Neural Regeneration Research 2025年第4期20卷 1098-1100页

作者： Jae-Hong Kim Ruqayya Afridi Il-Sung Jang Maan Gee Lee Kyoungho Suk Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of Pharmacology School of DentistryKyungpook National UniversityDaeguRepublic of Korea Brain Science&Engineering institute Kyungpook National UniversityDaeguRepublic of Korea

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s *** astrocytic regulation of neuronal activity has been increasingly recognized in recent *** are now recognized as playing a more complex role than mere bystanders in the central nervous ***,their role in regulating the sleep neurocircuitry is not well *** this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the *** briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

关键词： sleep ventrolateral astrocytes

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The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells

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International Journal of Oral Science 2017年第3期9卷 145-150页

作者： stian a engen gro h rørvik olav schreurs inger js blix karl schenck department of oral biology faculty of dentistryuniversity of osloOsloNorway institute of clinical dentistry faculty of dentistryuniversity of osloOsloNorway

Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. *** activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.

关键词： aryl hydrocarbon receptor commensal inflammation oral epithelium prostaglandin E2 Streptococcus

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Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral Science 2013年第3期5卷 130-140页

作者： Carol L Fischer Katherine S Walters David R Drake Deborah V Dawson Derek R Blanchette Kim A Brogden Philip W Wertz Dows institute for Dental Research College of Dentistry The University of Iowa Central Microscopy Research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

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Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era

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National Science Review 2022年第10期9卷 230-242页

作者： Chun Xu Chang Lei Sepanta Hosseinpour Saso Ivanovski Laurence J.Walsh Ali Khademhosseini School of dentistry The University of Queensland Centre for Orofacial Regeneration Reconstruction and Rehabilitation (COR3) School of Dentistry The University of Queensland Australian institute for Bioengineering and Nanotechnology The University of Queensland Terasaki institute for Biomedical Innovation

Following the global COVID-19 pandemic,nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools,vaccines and antiviral treatment for this novel virus(SARS-CoV-2).In this review,we first summarize nanotechnology with regard to the detection of SARS-C oV-2,including nanoparticle-based techniques such as rapid antigen testing,and nanopore-based se quencing and sensing *** we investigate nanote chnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 *** also highlight nanotechnology for the post-pandemic era,by providing tools for the battle with SARS-C oV-2 variants and for enhancing the global distribution of *** not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention,rapid diagnosis,vaccines and antiviral drugs of possible future virus outbreaks.

关键词： COVID-19 nanotechnology SARS-CoV-2 diagnosis vaccines

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Input of microenvironmental regulation on colorectal cancer: Role of the CCN family

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World Journal of Gastroenterology 2014年第22期20卷 6826-6831页

作者： Cheng-Chi Chang Been-Ren Lin Tai-Sheng Wu Yung-Ming Jeng Min-Liang Kuo Graduate institute of Oral Biology Graduate Institute of Clinical DentistrySchool of DentistryNational Taiwan University Department of dentistry National Taiwan University Hospital Department of Surgery National Taiwan University Hospital Graduate institute of Clinical dentistry School of DentistryNational Taiwan University Department of Pathology National Taiwan University institute of Biochemical Sciences College of Life ScienceNational Taiwan University institute of Toxicology College of Medicine National Taiwan University institute of Biological Chemistry

Colorectal cancer(CRC)is a major health problem causing significant morbidity and *** results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment,emphasizing the complex interacting network between cancer cells and nearby host cells,which triggers diverse signaling pathways to promote the growth and spread ofcancer *** CCN family proteins share a uniform modular structure,mediating a variety of physiological functions,including proliferation,apoptosis,migration,adhesion,differentiation,and ***,CCN proteins are also involved in CRC initiation and *** studies have shown that CCN members,such as CCN1,CCN2,CCN3,Wnt-induced secreted protein(WISP)-1,WISP-2,and WISP-3,are dysregulated in CRC,which implies potential diagnostic markers or therapeutic targets *** this review,we summarize the research findings on the role of CCN family proteins in CRC initiation,development,and progression,highlighting their potential for diagnosis,prognosis,and therapeutic application.

关键词： Microenvironment Colorectal cancer CCN proteins Tumorigenicity Cancer progression

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Bacterial entombment by intratubular mineralization following orthograde mineral trioxide aggregate obturation: a scanning electron microscopy study

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International Journal of Oral Science 2014年第4期6卷 227-232页

作者： Jun Sang Yoo Seok-Woo Chang So Ram Oh Hiran Perinpanayagam Sang-Min Lim Yeon-Jee Yoo Yeo-Rok Oh Sang-Bin Woo Seung-Hyun Han Qiang Zhu Kee-Yeon Kum Department of dentistry U Dental Hospital Department of Conservative dentistry School of Dentistry Kyung Hee University Department of Conservative dentistry Dental Research Institute Seoul National University Dental Hospital Seoul National University School of Dentistry Division of Restorative dentistry Schulich School of Medicine & Dentistry University of Western Ontario Department of Conservative dentistry Jukjeon Dental Hospital College of Dentistry Dankook University Department of Oral Microbiology & Immunology Dental Research Institute and BK21 Program Seoul National University School of Dentistry Division of Endodontology Department of Oral Health and Diagnostic Sciences School of Dental Medicine University of Connecticut Health Center

The time domain entombment of bacteria by intratubular mineralization following orthograde canal obturation with mineral trioxide aggregate（MTA） was studied by scanning electron microscopy（SEM）. Single-rooted human premolars（n560） were instrumented to an apical size #50/0.06 using ProF ile and treated as follows： Group 1（n510） was filled with phosphate buffered saline（PBS）; Group 2（n510） was incubated with Enterococcus faecalis for 3 weeks, and then filled with PBS; Group 3（n520） was obturated orthograde with a paste of OrthoM TA（BioM TA, Seoul, Korea） and PBS; and Group 4（n520） was incubated with E. faecalis for 3 weeks and then obturated with OrthoM TA–PBS paste. Following their treatments, the coronal openings were sealed with PBS-soaked cotton and intermediate restorative material（IRM）, and the roots were then stored in PBS for 1, 2, 4, 8 or 16 weeks. After each incubation period, the roots were split and their dentin/MTA interfaces examined in both longitudinal and horizontal directions by SEM. There appeared to be an increase in intratubular mineralization over time in the OrthoM TA-filled roots（Groups 3 and 4）. Furthermore, there was a gradual entombment of bacteria within the dentinal tubules in the E. faecalis inoculated MTA-filled roots（Group 4）. Therefore, the orthograde obturation of root canals with OrthoM TA mixed with PBS may create a favorable environment for bacterial entombment by intratubular mineralization.

关键词： bacterial entombment intratubular mineralization orthograde canal obturation scanning electron microscopy tag-like structure

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Dopaminergic effects on in vitro osteogenesis

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Bone Research 2015年第3期3卷 130-139页

作者： Dong Joon Lee Henry C Tseng Sing Wai Wong Zhengyan Wang Meng Deng Ching-Chang Ko NC Oral Health institute School of Dentistry University of North Carolina Duke Eye Center and Department of Ophthalmology Duke University Medical Center Oral Biology Program School of Dentistry University of North Carolina Department of Pediatric dentistry School of Dentistry University of North Carolina Department of Orthodontics School of Dentistry University of North Carolina

Multiple growth factors（e.g., BMP2, TGF-b1, FGF2） and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine（PDA） and dopamine（DA） monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA＇s role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. m RNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1–D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression（ALP, BSP, OC, OSX, RUNX2, and Collagen1a2） with or without receptor antagonists（SCH233390 and GR103691）. Two-way ANOVA was used for statistical analysis. All five DA receptors（D1, D2, D3, D4, and D5） m RNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days（P, 0.05）. Osteogenic mineralization was significantly greater in the DA-treated group than control group（P, 0.05）. Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair.

关键词： osteogenic differentiation cell proliferation polymerase chain reaction bone tissue engineering western blot analysis statistical analysis bone development gene expression nervous system growth factors in vitro

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Comparison of the rheological properties of four root canal sealers

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International Journal of Oral Science 2015年第1期7卷 56-61页

作者： Seok Woo Chang Young-Kyu Lee Qiang Zhu Won Jun Shon Woo Cheol Lee Kee Yeon Kum Seung Ho Baek In Bog Lee Bum-Soon Lim Kwang Shik Bae Department of Conservative dentistry School of Dentistry Kyung Hee University National Instrumentation Center for Environmental Management Seoul National University Department of Endodontology School of Dental Medicine University of Connecticut Health Center Department of Conservative dentistry Dental Research Institute School of Dentistry Seoul National University Dental Hospital Seoul National University Dental Research institute and Department of Dental Biomaterials School of Dentistry Seoul National University

The flowability of a root canal sealer is clinically important because it improves the penetration of the sealer into the complex root canal system. The purpose of this study was to compare the flowabilities of four root canal sealers, measured using the simple press method （ISO 6876）, and their viscosities, measured using a strain-controlled rheometer. A newly developed, calcium phosphate-based root canal sealer （Capseal） and three commercial root canal sealers （AH Plus, Sealapex and Pulp Canal Sealer EWT） were used in this study. The flowabilities of the four root canal sealers were measured using the simple press method （n= 5） and their viscosities were measured using a strain-controlled rheometer （n=5）. The correlation between these two values was statistically analysed using Spearman＇s correlation test. The flow diameters and the viscosities of the root canal sealers were strongly negatively correlated （p= -0.8618）. The viscosity of Pulp Canal Sealer EWT was the lowest and increased in the following order： AH Plus〈Sealapex〈Capseal （P〈0.05）. All of the tested root canal sealers showed characteristic time- and temperature-dependent changes in their rheological properties. The viscosities measured using the strain-controlled rheometer were more precise than the flowabilities measured using the simple press method, suggesting that the rheometer can accurately measure the rheological properties of root canal sealers.

关键词： Capseal rheological property root canal sealer strain-controlled rheometer

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