Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis o...Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis of T2D and is recognized as a potential risk factor for T2D.In recent years,increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D。展开更多
The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix component, which is located at the sk...The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix component, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degenerated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synaptophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.展开更多
Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure.The use of hydrogels with self-swelling properties may provide a higher bone ...Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure.The use of hydrogels with self-swelling properties may provide a higher bone augmentation,although swelling is generally considered to be a disadvantage in tissue engineering.Herein,a double-crosslinked gelatin-hyaluronic acid hydrogels(GH)with self-swelling properties were utilized.Meanwhile,niobium doped bioactive glasses(NbBG)was dispersed in the hydrogel network to prepare the GH-NbBG hydrogel.The composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the hydrogel.In vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of implantation.In addition,at the late stage after implantation,GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling pathway.Therefore,this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.展开更多
The Mg-Zn-Y-Nd alloy is a new type of degradable material for biomedical application. In the present study, Mg-6Zn-1.2Y-0.8Nd alloy was fabricated, and then extrusion and heat treatment were conducted to optimize its ...The Mg-Zn-Y-Nd alloy is a new type of degradable material for biomedical application. In the present study, Mg-6Zn-1.2Y-0.8Nd alloy was fabricated, and then extrusion and heat treatment were conducted to optimize its mechanical properties and cytocompatibility. The microstructure observation, mechanical property, degradation behavior and cytocompatibility tests were conducted on the Mg-Zn-Y-Nd alloy with three different states: as-cast(alloy C), as-extruded(alloy E) and extruded + heat treated(alloy EH).The results show that alloy C consists of coarse grains and continuous secondary phases. The extrusion process has caused incomplete recrystallization, and results in a mixed grain structure of elongated grains and small equiaxed grains(alloy E). The heat treatment process has promoted the recrystallization and homogenized the grain structure(alloy EH). Both the strength and ductility of the alloy has been improved by extrusion, but the following heat treatment has decreased the strength and increased the ductility.The degradation behavior of the alloy C and E alloys does not show much difference, but improves slightly in alloy EH, because the heat treatment has homogenized the microstructure and released the residual stress in the alloy. The directly and indirectly cell viability tests indicate that alloy EH exhibits the best cytocompatibility, which should be ascribed to its relative uniform degradation and low ion releasing rate. In summary, the combination of hot extrusion and heat treatment could optimize the mechanical property and cytocompatibility of the Mg-Zn-Y-Nd alloy together, which is beneficial for the future application of the alloy.展开更多
Oral cancer is a common malignant tumor of the head and neck,and surgery combined with radiotherapy and chemotherapy is the primary treatment modality.However,a positive resection margin that may lead to recurrence af...Oral cancer is a common malignant tumor of the head and neck,and surgery combined with radiotherapy and chemotherapy is the primary treatment modality.However,a positive resection margin that may lead to recurrence after surgery has always been a critical issue to address.Furthermore,radiotherapy and chemotherapy also have shortcomings such as resistance to chemotherapy and radiation,lack of targeting,and severe side effects.Therefore,exploring new methods of tumor surgical navigation and tumor treatment is of great significance for oral cancer.Although,the emerging near-infrared II(NIR-II,1,000–1,700 nm)region fluorescent imaging has revolutionized surgical navigation,a high tumor-targeting fluorescent probe remains lacking.Furthermore,while emerging photothermal therapy(PTT)can overcome chemoradiotherapy’s shortcomings and achieve precise treatment of tumors,its clinical application is still limited by the lack of high photothermal conversion efficiency,high photothermal stability,and highly penetrating materials.Herein,a NIR-II dye SQ890 is developed for tumor imaging and PTT of oral cancer.By assembling into nanoparticles(NPs)and being modified with epithelial growth factor receptor(EGFR)-targeting peptides GE11,SQ890 NPs-Pep can specifically accumulate in tumor sites via active targeting,and realize photoacoustic/NIR-II fluorescence dual-modality imaging-guided PTT of oral cancer.展开更多
Graphene oxide(GO)exhibits good mechanical and physicochemical characteristics and has extensive application prospects in bone tissue engineering.However,its effect on angiogenesis is unclear,and its potential toxic e...Graphene oxide(GO)exhibits good mechanical and physicochemical characteristics and has extensive application prospects in bone tissue engineering.However,its effect on angiogenesis is unclear,and its potential toxic effects are heavily disputed.Herein,we found that nanographene oxide(NGO)synthesized by one-step water electrolytic oxidation is smaller and shows superior biocompatibility.Moreover,NGO significantly enhanced angiogenesis in calvarial bone defect areas in vivo,providing a good microenvironment for bone regeneration.Endothelial tip cell differentiation is an important step in the initiation of angiogenesis.We verified that NGO activates endothelial tip cells by coupling with lysophosphatidic acid(LPA)in serum via strong hydrogen bonding interactions,which has not been reported.In addition,the mechanism by which NGO promotes angiogenesis was systematically studied.NGO-coupled LPA activates LPAR6 and facilitates the formation of migratory tip cells via Hippo/Yes-associated protein(YAP)independent of reactive oxygen species(ROS)stimulation or additional complex modifications.These results provide an effective strategy for the application of electrochemically derived NGO and more insight into NGO-mediated angiogenesis.展开更多
Concentrated growth factor(CGF)is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering.The host immune response,particularly macrophage activity,plays a critical...Concentrated growth factor(CGF)is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering.The host immune response,particularly macrophage activity,plays a critical role in injury repair and tissue regeneration.However,the biological effect of CGF on the immune response is not clear.To enrich the theoretical groundwork for clinical application,the present study examined the immunoregulatory role of CGF in macrophage functional activities in vitro.The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets,and it was biocompatible with macrophages.Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages.CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression,as detected by cell morphology and surface marker expression.A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin-1b while inducing expression of the chemokine regulated on activation,normal T cell expressed and secreted.Mechanistically,the AKT signaling pathway was activated,and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF.Our findings reveal that CGF induces a favorable immune response mediated by macrophages,which represents a promising strategy for functional tissue regeneration.展开更多
An abnormal displacement change observed during the holding period in nanoindentation tests on a zirconia dental ceramic was reported in this paper. It was found that, at the initial stage of the holding period, the m...An abnormal displacement change observed during the holding period in nanoindentation tests on a zirconia dental ceramic was reported in this paper. It was found that, at the initial stage of the holding period, the measured displacement versus time curves were similar in shape with the typical indentation creep curve reported in previous studies. As the holding lasted for long time, however, an evident reduction in displacement was observed for tests with high loading rate, implying that another unknown process, which might result in a decrease in displacement, would co-exist with creep during holding period. Elastic recovery was suggested to be one of the possible sources for such a displacement reduction. An empirical method was also proposed to eliminate the effect of this displacement reduction on the determination of hardness and Young's modulus.展开更多
Alveolar ridge atrophy brings great challenges for endosteal implantation due to the lack of adequate vertical bone mass to hold the implants.To overcome this limitation,we developed a novel dental implant design:sub-...Alveolar ridge atrophy brings great challenges for endosteal implantation due to the lack of adequate vertical bone mass to hold the implants.To overcome this limitation,we developed a novel dental implant design:sub-scaffold dental implant system(SDIS),which is composed of a metal implant and a micro-nano bioactive glass scaffold.This implant system can be directly implanted under mucous membranes without adding any biomolecules or destroying the alveolar ridge.To evaluate the performance of the novel implant system in vivo,SDISs were implanted into the subepicranial aponeurosis space of Sprague–Dawley rats.After 6 weeks,the SDIS and surrounding tissues were collected and analysed by micro-CT,scanning electron microscopy and histology.Our results showed that SDISs implanted into the sub-epicranial aponeurosis had integrated with the skull without any mobility and could stably support a denture.Moreover,this design achieved alveolar ridge augmentation,as active osteogenesis could be observed outside the cortical bone.Considering that the microenvironment of the sub-epicranial aponeurosis space is similar to that of the alveolar ridge,SDISs have great potential for clinical applications in the treatment of atrophic alveolar ridges.The study was approved by the Animal Care Committee of Guangdong Pharmaceutical University(approval No.2017370).展开更多
基金supported by the China Postdoctoral Science Foundation(No.2021M691484)。
文摘Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis of T2D and is recognized as a potential risk factor for T2D.In recent years,increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D。
基金supported by the National Natural Science Foundation of China,No.30900300/C1002
文摘The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix component, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degenerated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synaptophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.
基金This work was supported by the National Natural Science Foundation of China(No.32171311,32000933,82271025)the Natural Science Foundation of Guangdong Province(No.2019A1515110480).
文摘Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure.The use of hydrogels with self-swelling properties may provide a higher bone augmentation,although swelling is generally considered to be a disadvantage in tissue engineering.Herein,a double-crosslinked gelatin-hyaluronic acid hydrogels(GH)with self-swelling properties were utilized.Meanwhile,niobium doped bioactive glasses(NbBG)was dispersed in the hydrogel network to prepare the GH-NbBG hydrogel.The composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the hydrogel.In vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of implantation.In addition,at the late stage after implantation,GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling pathway.Therefore,this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.
基金the National Key Research and Development Program of China(No.2016YFC1102601)the Shenzhen Basic Research Project(JCYJ20170306141749970),the Shenzhen Basic Research Project(Nos.JCYJ2015052916222873,JCYJ20160407090231002,JCYJ20150625155931806 and JCYJ20160427100211076) for financial supportthe Shenzhen Technology Innovation Plan(Nos.CXZZ20140731091722497 and CXZZ20140419114548507)
文摘The Mg-Zn-Y-Nd alloy is a new type of degradable material for biomedical application. In the present study, Mg-6Zn-1.2Y-0.8Nd alloy was fabricated, and then extrusion and heat treatment were conducted to optimize its mechanical properties and cytocompatibility. The microstructure observation, mechanical property, degradation behavior and cytocompatibility tests were conducted on the Mg-Zn-Y-Nd alloy with three different states: as-cast(alloy C), as-extruded(alloy E) and extruded + heat treated(alloy EH).The results show that alloy C consists of coarse grains and continuous secondary phases. The extrusion process has caused incomplete recrystallization, and results in a mixed grain structure of elongated grains and small equiaxed grains(alloy E). The heat treatment process has promoted the recrystallization and homogenized the grain structure(alloy EH). Both the strength and ductility of the alloy has been improved by extrusion, but the following heat treatment has decreased the strength and increased the ductility.The degradation behavior of the alloy C and E alloys does not show much difference, but improves slightly in alloy EH, because the heat treatment has homogenized the microstructure and released the residual stress in the alloy. The directly and indirectly cell viability tests indicate that alloy EH exhibits the best cytocompatibility, which should be ascribed to its relative uniform degradation and low ion releasing rate. In summary, the combination of hot extrusion and heat treatment could optimize the mechanical property and cytocompatibility of the Mg-Zn-Y-Nd alloy together, which is beneficial for the future application of the alloy.
基金supported by the National Natural Science Foundation of China(Nos.81773642 and 52073139)the Postdoctoral Research Foundation of China(Nos.2020TQ0253 and 2020M682927).
文摘Oral cancer is a common malignant tumor of the head and neck,and surgery combined with radiotherapy and chemotherapy is the primary treatment modality.However,a positive resection margin that may lead to recurrence after surgery has always been a critical issue to address.Furthermore,radiotherapy and chemotherapy also have shortcomings such as resistance to chemotherapy and radiation,lack of targeting,and severe side effects.Therefore,exploring new methods of tumor surgical navigation and tumor treatment is of great significance for oral cancer.Although,the emerging near-infrared II(NIR-II,1,000–1,700 nm)region fluorescent imaging has revolutionized surgical navigation,a high tumor-targeting fluorescent probe remains lacking.Furthermore,while emerging photothermal therapy(PTT)can overcome chemoradiotherapy’s shortcomings and achieve precise treatment of tumors,its clinical application is still limited by the lack of high photothermal conversion efficiency,high photothermal stability,and highly penetrating materials.Herein,a NIR-II dye SQ890 is developed for tumor imaging and PTT of oral cancer.By assembling into nanoparticles(NPs)and being modified with epithelial growth factor receptor(EGFR)-targeting peptides GE11,SQ890 NPs-Pep can specifically accumulate in tumor sites via active targeting,and realize photoacoustic/NIR-II fluorescence dual-modality imaging-guided PTT of oral cancer.
基金This study was supported by the National Natural Science Foundation of China(No.52072167,81900989)the Natural Science Foundation of Guangdong Province(2019A1515011980)the Guangdong Basic and Applied Basic Research Foundation(2019A1515110088).
文摘Graphene oxide(GO)exhibits good mechanical and physicochemical characteristics and has extensive application prospects in bone tissue engineering.However,its effect on angiogenesis is unclear,and its potential toxic effects are heavily disputed.Herein,we found that nanographene oxide(NGO)synthesized by one-step water electrolytic oxidation is smaller and shows superior biocompatibility.Moreover,NGO significantly enhanced angiogenesis in calvarial bone defect areas in vivo,providing a good microenvironment for bone regeneration.Endothelial tip cell differentiation is an important step in the initiation of angiogenesis.We verified that NGO activates endothelial tip cells by coupling with lysophosphatidic acid(LPA)in serum via strong hydrogen bonding interactions,which has not been reported.In addition,the mechanism by which NGO promotes angiogenesis was systematically studied.NGO-coupled LPA activates LPAR6 and facilitates the formation of migratory tip cells via Hippo/Yes-associated protein(YAP)independent of reactive oxygen species(ROS)stimulation or additional complex modifications.These results provide an effective strategy for the application of electrochemically derived NGO and more insight into NGO-mediated angiogenesis.
基金supported by the National Natural Science Foundation of China(81900989,81870786)the Guangdong Basic and Applied Basic Research Foundation(2021A1515012475)the China Postdoctoral Science Foundation(2020M672548).
文摘Concentrated growth factor(CGF)is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering.The host immune response,particularly macrophage activity,plays a critical role in injury repair and tissue regeneration.However,the biological effect of CGF on the immune response is not clear.To enrich the theoretical groundwork for clinical application,the present study examined the immunoregulatory role of CGF in macrophage functional activities in vitro.The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets,and it was biocompatible with macrophages.Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages.CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression,as detected by cell morphology and surface marker expression.A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin-1b while inducing expression of the chemokine regulated on activation,normal T cell expressed and secreted.Mechanistically,the AKT signaling pathway was activated,and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF.Our findings reveal that CGF induces a favorable immune response mediated by macrophages,which represents a promising strategy for functional tissue regeneration.
文摘An abnormal displacement change observed during the holding period in nanoindentation tests on a zirconia dental ceramic was reported in this paper. It was found that, at the initial stage of the holding period, the measured displacement versus time curves were similar in shape with the typical indentation creep curve reported in previous studies. As the holding lasted for long time, however, an evident reduction in displacement was observed for tests with high loading rate, implying that another unknown process, which might result in a decrease in displacement, would co-exist with creep during holding period. Elastic recovery was suggested to be one of the possible sources for such a displacement reduction. An empirical method was also proposed to eliminate the effect of this displacement reduction on the determination of hardness and Young's modulus.
基金This study was financially supported by the National Key Research and Development Program of China(No.2018YFC1106300)the China Postdoctoral Science Foundation(No.2020M672732)+2 种基金the Natural Science Foundation of Guangdong Province of China(No.2019A1515110480)the Medical Scientific Research Foundation of Guangdong Province of China(No.A2020107)the Beijing Municipal Health Commission of China(Nos.BMHC-2019-9,BMHC-2018-4,PXM2020_026275_000002).
文摘Alveolar ridge atrophy brings great challenges for endosteal implantation due to the lack of adequate vertical bone mass to hold the implants.To overcome this limitation,we developed a novel dental implant design:sub-scaffold dental implant system(SDIS),which is composed of a metal implant and a micro-nano bioactive glass scaffold.This implant system can be directly implanted under mucous membranes without adding any biomolecules or destroying the alveolar ridge.To evaluate the performance of the novel implant system in vivo,SDISs were implanted into the subepicranial aponeurosis space of Sprague–Dawley rats.After 6 weeks,the SDIS and surrounding tissues were collected and analysed by micro-CT,scanning electron microscopy and histology.Our results showed that SDISs implanted into the sub-epicranial aponeurosis had integrated with the skull without any mobility and could stably support a denture.Moreover,this design achieved alveolar ridge augmentation,as active osteogenesis could be observed outside the cortical bone.Considering that the microenvironment of the sub-epicranial aponeurosis space is similar to that of the alveolar ridge,SDISs have great potential for clinical applications in the treatment of atrophic alveolar ridges.The study was approved by the Animal Care Committee of Guangdong Pharmaceutical University(approval No.2017370).