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A viscoelastic alginate-based hydrogel network coordinated with spermidine for periodontal ligament regeneration

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Regenerative Biomaterials 2023年第1期10卷 510-521页

作者： Songbai Zhang Yuanbo Jia Jingyi Liu Fan Feng Zhao Wei Min Zhang Feng Xu State Key Laboratory of Military Stomatology&National Clinical research center for Oral diseases&Shaanxi International joint research center for Oral diseases Department of General Dentistry and EmergencySchool of StomatologyFourth Military Medical UniversityXi’an 710032P.R.China The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and TechnologyXi’an Jiaotong UniversityXi’an 710049P.R.China Bioinspired Engineering and Biomechanics center(BEBC) Xi’an Jiaotong UniversityXi’an 710049P.R.China

Periodontitis can cause irreversible defects in the periodontal ligament(PDL),the regeneration of which is the major obstacle to the clinical treatment of *** hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL ***,existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium,which may have been shown as an important role in tissue ***,the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain *** this study,we developed a bi-crosslinking viscoelastic hydrogel(Alg-PBA/Spd)by integrating phenylboronic acid-modified alginate with anti-inflammatory agent(spermidine)through borate ester and B-N coordination bonds,where spermidine will be released with the degradation of the ***-PBA/Spd hydrogel is biocompatible,injectable and can quickly adapt to complex periodontal structures due to the dynamic *** demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal *** results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.

关键词： periodontal regeneration viscoelastic hydrogel mechano-biochemically synergistic treatment mechanical microenvironment

MACF1 deficiency suppresses tooth mineralization through IGF1 mediated crosstalk between odontoblasts and ameloblasts

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Genes & diseases 2024年第5期11卷 9-12页

作者： Wuxia Qiu Xiao Lin Shaoqing Yang Zhihao Chen Kewen Zhang Chaofei Yang Yu Li Zhiping Miao Xiaoni Deng Xiaohong Duan Airong Qian Lab for bone Metabolism Xi’an Key Laboratory of Special Medicine and Health EngineeringKey Lab for Space Biosciences and BiotechnologyResearch Center for Special Medicine and Health Systems EngineeringNPU-UAB Joint Laboratory for Bone MetabolismSchool of Life SciencesNorthwestern Polytechnical UniversityXi’anShaanxi 710072China State Key Laboratory of Military Stomatology National Clinical Research Center for Oral DiseasesDepartment of Oral BiologyClinic of Oral Rare and Genetic DiseasesSchool of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi 710032China School of Chemical Engineering Sichuan University of Science&EngineeringZigongSichuan 643000China research&Development Institute of Northwestern Polytechnical University in Shenzhen ShenzhenGuangdong 518063China Puyang Institute of Technology Henan UniversityPuyangHenan 457000China

Tooth mineralization is a ubiquitous and tightly regulated process involving complicated interactions between dental epithelium and *** molecules in tooth mineralization remain poorly *** actin cross-linking factor 1(MACF1)is a spectraplakin protein that plays pivotal roles in the brain,muscle,lung,and bone developmental process.^(1-3) To study the specific functions of MACF1 in bone formation,we established Macf1 conditional knockout mice using the Cre-LoxP system driven by Osxterix promoter(Osx-Cre;Macf1^(f/f)).^(2) Not surprisingly,Osx-Cre;Macf1^(f/f) mice displayed the phenotypes of delayed ossification and decreased bone ***,the OsxCre;Macf1^(f/f) mice unexpectedly showed a white and opaque appearance of incisors,contrary to the normal yellowbrown and transparent *** Osxterix is expressed in dental mesenchyme during tooth development,the abnormal tooth appearance might imply a new function of MACF1 in odontoblasts,or even ***,the present study aimed to investigate the role of MACF1 during tooth development.

关键词： mineralization linking transparent

Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3086-3109页

作者： Yihang Hao Haofan Wang Xianggen Liu Wenrui Gai Shilong Hu Wencheng Liu Zhuang Miao Yu Gan Xianghua Yu Rongjia Shi Yongzhen Tan Ting Kang Ao Hai Yi Zhao Yihang Fu Yaling Tang Ling Ye Jin Liu Xinhua Liang Bowen Ke State Key Laboratory of Oral diseases and National Clinical research center for Oral diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China College of Computer Science Sichuan UniversityChengdu 610065China Department of Anesthesiology Laboratory of Anesthesia and Critical Care MedicineNational-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic *** primary challenge is to integrate diverse pharmacophores within a single-molecule *** address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local *** integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound *** framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent *** a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal *** insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome *** findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.

关键词： Multifunctional drugs Deep simulated annealing Molecule generation Articaine derivatives AI-enhanced drug discovery

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

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Chinese Chemical Letters 2024年第1期35卷 371-378页

作者： Ran Tian Xinyu Qiu Wenyun Mu Bolei Cai Zhongning Liu Shiyu Liu Xin Chen School of Chemical Engineering and Technology Department of Chemical EngineeringShaanxi Key Laboratory of Energy Chemical Process IntensificationXi'an Jiao Tong UniversityXi'an 710049China School of Stomatology State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral DiseasesDepartment of Preventive DentistryThe Fourth Military Medical UniversityXi'an 710032China School of Stomatology State Key Laboratory of Military StomatologyDepartment of Oral and Maxillofacial SurgeryThe Fourth Military Medical UniversityXi'an 710032China Department of Prosthodontics Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China School of Stomatology State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringThe Fourth Military Medical UniversityXi'an 710032China

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer ***,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection *** hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed *** bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose ***,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

关键词： Smart hydrogel with self-adaptable size Breast cancer therapy Dual responsive cargoes release Selective tumor elimination On-demand adipose tissue regeneration Effective bacteria inhibition

circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

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International Journal of Oral Science 2022年第3期14卷 360-370页

作者： Liyuan Yu Kai Xia Jing Zhou Zhiai Hu Xing Yin Chenchen Zhou Shujuan Zou Jun Liu State Key Laboratory of Oral diseases&National Clinical research center for Oral diseases&Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Stomatology Kunming Yan’an hospitalKunmingChina State Key Laboratory of Oral diseases&National Clinical research center for Oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue *** RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell ***,how circRNAs regulate hASCs in osteogenesis is still ***,we found circ_0003204 was significantly downregulated during osteogenic differentiation of *** of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of *** performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging *** predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m *** following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 *** in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect *** findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

关键词： regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis miR

Total knee arthroplasty for treatment of post-traumatic arthritis: Systematic review

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World Journal of Orthopedics 2016年第9期7卷 584-591页

作者： Hesham Saleh Stephen Yu Jonathan Vigdorchik Ran Schwarzkopf Division of Adult Reconstruction Department of Orthoapedic Surgery New York University Langone Medical Center Hospital for Joint Diseases

AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for Englishlanguage clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved *** extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and *** Sixteen studies, four prospective and ten retrospective,examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion(ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene *** Although associated with higher complication rates,TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes.

关键词： Total knee arthroplasty Post-traumatic arthritis Tibial plateau fracture Distal femur fracture Patella fracture

Drug-loading ZIF-8 for modification of microporous bone scaffold to promote vascularized bone regeneration

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Chinese Chemical Letters 2024年第6期35卷 358-364页

作者： Xin Zhang Junyu Chen Xiang Pei Linxin Yang Liang Wang Luona Chen Guangmei Yang Xibo Pei Qianbing Wan Jian Wang State Key Laboratory of Oral diseases National Clinical Research Center for Oral DiseasesChengdu 610041China Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengdu 610041China

Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue *** at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone *** osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable ***,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone *** processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these ***,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted *** conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.

关键词： Drug-loading nanoparticles Surface coating Microporous bone scaffold Vascularization bone regeneration

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of Oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Orthopedic Surgery and Orthopedic research Institute West China HospitalSichuan UniversityChengduChina

bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 ***, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

关键词： Sema3A formation overload

Berberine mediates root remodeling in an immature tooth with apical periodontitis by regulating stem cells from apical papilla differentiation

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International Journal of Oral Science 2020年第2期12卷 172-181页

作者： Yujia Cui Jing Xie Yujie Fu Chuwen Li Liwei Zheng Dingming Huang Changchun Zhou Jianxun Sun Xuedong Zhou State Key Laboratory of Oral diseases&National Clinical center for Oral diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral diseases&National Clinical center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Shanghai Key Laboratory of Stomatology and Shanghai research Institute of Stomatology&National Clinical research center for Oral diseases&Department of Oral and Maxillofacial-Head Neck Oncology Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Oral diseases&National Clinical research center for Oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina and 5National Engineering Research Center for BiomaterialsSichuan UniversityChengduChina

Once pulp necrosis or apical periodontitis occurs on immature teeth,the weak root and open root apex are challenging to ***(BBR)is a potential medicine for bone disorders,therefore,we proposed to apply BBR in root canals to enhance root repair in immature *** in vivo model of immature teeth with apical periodontitis was established in rats,and root canals were filled with BBR,calcium hydroxide or sterilized saline for 3 *** shape of the roots was analyzed by micro-computed tomography and histological *** vitro,BBR was introduced into stem cells from apical papilla(SCAPs).Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity,mineralization ability,and gene expression of osteogenic *** signaling pathway,which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR,Western blot analysis,and *** rats treated with BBR,more tissue was formed,with longer roots,thicker root walls,and smaller apex *** addition,we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent *** induced the expression ofβ-catenin and enhancedβ-catenin entering into the nucleus,to up-regulate more runt-related nuclear factor 2 *** enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.

关键词： roots walls filled