Bone is consisted of bone matrix,cells and bioactive factors,and bone matrix is the combination of inorganic minerals and organic polymers.Type I collagen fibril made of five triple-helical collagen chains is the main...Bone is consisted of bone matrix,cells and bioactive factors,and bone matrix is the combination of inorganic minerals and organic polymers.Type I collagen fibril made of five triple-helical collagen chains is the main organic polymer in bone matrix.It plays an important role in the bone formation and remodeling process.Moreover,collagen is one of the most commonly used scaffold materials for bone tissue engineering due to its excellent biocompatibility and biodegradability.However,the low mechanical strength and osteoinductivity of collagen limit its wider applications in bone regeneration field.By incorporating different biomaterials,the properties such as porosity,structural stability,osteoinductivity,osteogenicity of collagen matrixes can be largely improved.This review summarizes and categorizes different kinds of biomaterials including bioceramic,carbon and polymer materials used as components to fabricate collagen based composite scaffolds for bone regeneration.Moreover,the possible directions of future research and development in this field are also proposed.展开更多
The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field,such as collagen or hyaluronic acid,etc.However,the biosafety and efficacy of ...The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field,such as collagen or hyaluronic acid,etc.However,the biosafety and efficacy of these implants are still challenged.In this study,a skin damage animal model was prepared by UV-photoaging and recombinant humanized type Ⅲ collagen(rhCol Ⅲ)was applied as a bioactive material to implant in vivo to study its biological effect,comparing with saline and uncrosslinked hyaluronic acid(HA).Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment.Histological observation,specific gene expression and other molecular biological methods were applied by the end of the animal experiment.The results indicated that rhCol Ⅲ could alleviate the skin photoaging caused by UV radiation,including reduce the thickening of epidermis and dermis,increase the secretion of Collagen Ⅰ(Col Ⅰ)and Collagen Ⅲ(Col Ⅲ)and remodel of extracellular matrix(ECM).Although the cell-material interaction and mechanism need more investigation,the effect of rhCol Ⅲ on damaged skin was discussed from influence on cells,reconstruction of ECM,and stimulus of small biological molecules based on current results.In conclusion,our findings provided rigorous biosafety information of rhCol Ⅲ and approved its potential in skin repair and regeneration.Although enormous efforts still need to be made to achieve successful translation from bench to clinic,the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.展开更多
Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach i...Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.展开更多
Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory mechanisms.In this study,we identified the epigenetic landscape along the devel...Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory mechanisms.In this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone dysplasia.We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter region.Notably,inhibition of glycolysis improved the function of SSCs despite Ptip deficiency.To the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic control.This framework is expected to improve SSC-based treatments of bone developmental disorders.展开更多
Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process re...Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process remain unclear.Long noncoding RNAs(lnc RNAs)are a newly identified class of functional RNAs that regulate cellular processes,such as gene expression and translation regulation.Recently,lnc RNAs have been reported to be involved in osteogenesis and bone formation.However,as the most abundant noncoding RNAs in vivo,the potential regulatory role of lnc RNAs in osteoclast formation and bone resorption urgently needs to be clarified.We recently found that the lnc RNA Nron(long noncoding RNA repressor of the nuclear factor of activated T cells)is highly expressed in osteoclast precursors.Nron is downregulated during osteoclastogenesis and bone ageing.To further determine whether Nron regulates osteoclast activity during orthodontic treatment,osteoclastic Nron transgenic(Nron c TG)and osteoclastic knockout(Nron CKO)mouse models were generated.When Nron was overexpressed,the orthodontic tooth movement rate was reduced.In addition,the number of osteoclasts decreased,and the activity of osteoclasts was inhibited.Mechanistically,Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation.In contrast,by deleting Nron specifically in osteoclasts,tooth movement speed increased in Nron CKO mice.These results indicate that lnc RNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.展开更多
Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical regi...Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.展开更多
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...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 in vitro and in vivo,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 in vivo 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.展开更多
The dental operative microscope has been widely employed in the field of dentistry,particularly in endodontics and operative dentistry,resulting in significant advancements in the effectiveness of root canal therapy,e...The dental operative microscope has been widely employed in the field of dentistry,particularly in endodontics and operative dentistry,resulting in significant advancements in the effectiveness of root canal therapy,endodontic surgery,and dental restoration.However,the improper use of this microscope continues to be common in clinical settings,primarily due to operators’insufficient understanding and proficiency in both the features and established operating procedures of this equipment.In October 2019,Professor Jingping Liang,Vice Chairman of the Society of Cariology and Endodontology,Chinese Stomatological Association,organized a consensus meeting with Chinese experts in endodontics and operative dentistry.The objective of this meeting was to establish a standard operation procedure for the dental operative microscope.Subsequently,a consensus was reached and officially issued.Over the span of about four years,the content of this consensus has been further developed and improved through practical experience.展开更多
Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque.It remains challenges for current practice to specifically identify,interven...Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque.It remains challenges for current practice to specifically identify,intervene and interrupt the development of caries while restoring defects.In this study,inspired by natural dental plaque,a stimuli-responsive multidrug delivery system(PMs@NaF-SAP)has been developed to prevent tooth decay and promote enamel restoration.Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond,followed by conjugation with salivary-acquired peptide(SAP)to endow the nanoparticle with strong adhesion to tooth enamel.The constructed PMs@NaF-SAP specifically adheres to tooth,identifies cariogenic conditions and intelligently releases drugs at acidic pH,thereby providing antibacterial adhesion and cariogenic biofilm resistance,and restoring the microarchitecture and mechanical properties of demineralized teeth.Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues.These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.展开更多
A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged ...A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.展开更多
In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing ...In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing self-healing,however,the mechanism is unclear.Using this type of fracture mouse model,we discovered the activation of Hedgehog(Hh)signaling in the injured growth plate,which could activate chondrocytes in growth plate and promote cartilage repair.展开更多
Tongue squamous cell carcinoma is highly malignant and has a poor prognosis.In this study,we aimed to combine whole-genome sequencing,whole-genome methylation,and whole-transcriptome analyses to understand the molecul...Tongue squamous cell carcinoma is highly malignant and has a poor prognosis.In this study,we aimed to combine whole-genome sequencing,whole-genome methylation,and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better.Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples.After multi-omics sequencing,differentially methylated intervals,methylated loop sites,methylated promoters,and transcripts were screened for variation in all paired samples.Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma.We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels.Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade,which is associated with cancer progression and the development of drug resistance during treatment.The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings.We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs.Collectively,changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.展开更多
Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in...Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages phenotype.In a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.展开更多
Personalized precision therapy and rapid osseointegration are the main development directions of dental implants.3 D printing is a vital advanced manufacturing technology for personalized precision therapy.However,the...Personalized precision therapy and rapid osseointegration are the main development directions of dental implants.3 D printing is a vital advanced manufacturing technology for personalized precision therapy.However,the osteogenesis of the 3 D printed Ti6 Al4 V implants is unsatisfactory.From the bionic perspective,the hierarchical micro/nano-topography can mimic the microenvironment of the multilevel structure of natural bone tissue and may endow the implant surface with superior bioactivity.In the present study,the hierarchical micro/nano-topography was successfully fabricated by construction the nanoscale feature on 3 D printed microscale roughness surface of 3 D-printed Ti6 Al4 V implants by alkali-heat treatment and hydrothermal treatment.Then the cell biological responses in vitro and osseointegration performance in vivo were systematically evaluated.The hierarchical micro/nano-topography evidently increased the roughness,improved the hydrophilicity and accelerated the hydroxyapatite deposition and mineralization,which significantly enhanced the adhesion,differentiation and extracellular matrix mineralization of bone marrow derived mesenchymal stromal cells(BMSCs).Most importantly,the hierarchical micro/nano-topography on 3 D-printed implants facilitated the new bone formation and rapid osseointegration in vivo.Our study suggested that 3 D-printed implant with micro/nano-topography may be a promising candidate to be applied in orthopedic field to meet the need of customized therapy and rapid osseointegration.展开更多
Periodontitis is a prevalent oral disease. It can cause tooth loss and has a significant impact on patients’ quality of life. While existing treatments can only slow the progression of periodontitis, they are unable ...Periodontitis is a prevalent oral disease. It can cause tooth loss and has a significant impact on patients’ quality of life. While existing treatments can only slow the progression of periodontitis, they are unable to achieve complete regeneration and functional reconstruction of periodontal tissues. As a result, regenerative therapies based on biomaterials have become a focal point of research in the field of periodontology. Despite numerous studies reporting the superiority of new materials in periodontal regeneration, limited progress has been made in translating these findings into clinical practice. This may be due to the lack of appropriate animal models to simulate the tissue defects caused by human periodontitis. This review aims to provide an overview of established animal models for periodontal regeneration, examine their advantages and limitations, and outline the steps for model construction. The objective is to determine the most relevant animal models for periodontal regeneration based on the hypothesis and expected outcomes.展开更多
The authors regret that there are errors in the article Fig.8A and Fig.S22A due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading.Although it does not affect...The authors regret that there are errors in the article Fig.8A and Fig.S22A due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading.Although it does not affect the conclusion,these are obvious errors.The authors have now modified as below.The original data of these figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.The authors apologize for any inconvenience caused to the journal and readers.展开更多
As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent sensors.However,the CDs with deep-red(DR)or near-infrared(NIR)emis...As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent sensors.However,the CDs with deep-red(DR)or near-infrared(NIR)emission have rarely been reported.In this work,we prepared deep-red emissive fluorine-doped carbon quantum dots(F-CDs)by introducing a precursor simultaneously containing fluorine and amidogen.The synergistic effect of nitrogen doping and D-π-A pattern production contributed to the maximum emission of F-CDs at 636 nm with an absolute quantum yield of 36.00%±0.68%.Moreover,we designed an F-CDs-based fluorescence assay to determine the content of hypochlorite(ClO^(-)),with a limit of detection(LOD)as low as 15.4 nmol/L,indicating the high sensitivity of F-CDs to ClO^(-).In real samples,the F-CDs-based fluorescent sensor exhibited excellent sensitivity and selectivity in the detection of ClO^(-),with an error below 2%,suggesting their great potential in daily life.In cancer cell imaging,the F-CDs not only demonstrated high sensitivity to ClO^(-)but also exhibited excellent mitochondria targeting,as evidenced by the high Pearson's correlation coefficient(PCC)of 0.93 in colocalization analysis.The work presented here suggests the great potential of replacing commercial dyes with F-CDs for highly specific mitochondria labeling and cell imaging.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell ma...Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid tumors.However,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector function of CAR-T cells,leading to a relapse rate of up to 75%in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies.Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.In this review,we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy.These insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.展开更多
Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects.Recent studies have shown that appropriate inflammatory and immune cells are essen...Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects.Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials.Previous studies have mainly focused on innate immune cells such as macrophages.In our previous work,we found that T lymphocytes,as adaptive immune cells,are also essential in the osteoinduction procedure.As the most important antigen-presenting cell,whether dendritic cells(DCs)can recognize non-antigen biomaterials and participate in osteoinduction was still unclear.In this study,we found that surgical trauma associated with materials implantation induces necrocytosis,and this causes the release of high mobility group protein-1(HMGB1),which is adsorbed on the surface of bone substitute materials.Subsequently,HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells,and the inflammatory response was activated.Finally,activated DCs release regeneration-related chemokines,recruit mesenchymal stem cells,and initiate the osteoinduction process.This study sheds light on the immune-regeneration process after bone substitute materials implantation,points out a potential direction for the development of bone substitute materials,and provides guidance for the development of clinical surgical methods.展开更多
Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush mo...Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush modified mesoporous hydroxyapatite(MHA-SIM-P)loaded with simvastatin(SIM)using an ovariectomised(OVX)rat model.Quantitative alkaline phosphatase activity assay,alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro.The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells(BMSCs)in vitro.In osteoporotic animal model,the therapeutic efficiency for bone defect was evaluated byμCT analysis,tartrateresistant acid phosphatase,haematoxylin and eosin staining,which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks.This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis.Thus,this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.展开更多
基金The authors gratefully acknowledge the support of the National Natural Science Foundation of China(No.81672134)Science and Technology Commission of Shanghai Municipality(No.15441905300,17510710800,16DZ0503800).
文摘Bone is consisted of bone matrix,cells and bioactive factors,and bone matrix is the combination of inorganic minerals and organic polymers.Type I collagen fibril made of five triple-helical collagen chains is the main organic polymer in bone matrix.It plays an important role in the bone formation and remodeling process.Moreover,collagen is one of the most commonly used scaffold materials for bone tissue engineering due to its excellent biocompatibility and biodegradability.However,the low mechanical strength and osteoinductivity of collagen limit its wider applications in bone regeneration field.By incorporating different biomaterials,the properties such as porosity,structural stability,osteoinductivity,osteogenicity of collagen matrixes can be largely improved.This review summarizes and categorizes different kinds of biomaterials including bioceramic,carbon and polymer materials used as components to fabricate collagen based composite scaffolds for bone regeneration.Moreover,the possible directions of future research and development in this field are also proposed.
基金financially supported by the National Key Research and Development Program of China(2018YFC1106200 and 2018YFC1106203)the National Natural Science Foundation of China(32071330).
文摘The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field,such as collagen or hyaluronic acid,etc.However,the biosafety and efficacy of these implants are still challenged.In this study,a skin damage animal model was prepared by UV-photoaging and recombinant humanized type Ⅲ collagen(rhCol Ⅲ)was applied as a bioactive material to implant in vivo to study its biological effect,comparing with saline and uncrosslinked hyaluronic acid(HA).Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment.Histological observation,specific gene expression and other molecular biological methods were applied by the end of the animal experiment.The results indicated that rhCol Ⅲ could alleviate the skin photoaging caused by UV radiation,including reduce the thickening of epidermis and dermis,increase the secretion of Collagen Ⅰ(Col Ⅰ)and Collagen Ⅲ(Col Ⅲ)and remodel of extracellular matrix(ECM).Although the cell-material interaction and mechanism need more investigation,the effect of rhCol Ⅲ on damaged skin was discussed from influence on cells,reconstruction of ECM,and stimulus of small biological molecules based on current results.In conclusion,our findings provided rigorous biosafety information of rhCol Ⅲ and approved its potential in skin repair and regeneration.Although enormous efforts still need to be made to achieve successful translation from bench to clinic,the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.
基金supported by grants from the National Key R&D Program of China(2021YFA1100600 to S.S.)the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125,D-07 to S.S.,D-11 to X.K.)+5 种基金the Pearl River Talent Recruitment Program(2019ZT08Y485)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX10302207-001-002)the Sun Yat-sen University Young Teacher Key Cultivation Project(18ykzd05 to X.K.)the Natural Science Foundation of Guangdong(2016A030313262 to X.M.)the National Natural Science Foundation of China(82170924 to X.K.,81700928 to L.M.)the Youth Teacher Training Project of Sun Yat-sen University(17ykpy71 to L.M.).
文摘Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.
基金supported by the National Key Research and Development Program of China(2022YFA0103200)the National Natural Science Foundation of China(82325003,82230007,82200188,82270956 and 82171568)+1 种基金the National Defense Biotechnology Outstanding Young Talents Fund(01-SWKJYCJJ24)Shaanxi Province Innovation Capability Support Program Scientific and Technological Innovation Team(2023-CX-TD-69).
文摘Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory mechanisms.In this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone dysplasia.We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter region.Notably,inhibition of glycolysis improved the function of SSCs despite Ptip deficiency.To the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic control.This framework is expected to improve SSC-based treatments of bone developmental disorders.
基金supported by grants from the National Natural Science Foundation Projects of China(81822012,81771043)National Science and Technology Major Project of China(2016YFC1102705)+1 种基金Special Fund of Chinese Central University for Basic Scientific Research(20173386)Training Program of Shanghai Municipal Health System for Excellent Talents(2017BR009)。
文摘Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process remain unclear.Long noncoding RNAs(lnc RNAs)are a newly identified class of functional RNAs that regulate cellular processes,such as gene expression and translation regulation.Recently,lnc RNAs have been reported to be involved in osteogenesis and bone formation.However,as the most abundant noncoding RNAs in vivo,the potential regulatory role of lnc RNAs in osteoclast formation and bone resorption urgently needs to be clarified.We recently found that the lnc RNA Nron(long noncoding RNA repressor of the nuclear factor of activated T cells)is highly expressed in osteoclast precursors.Nron is downregulated during osteoclastogenesis and bone ageing.To further determine whether Nron regulates osteoclast activity during orthodontic treatment,osteoclastic Nron transgenic(Nron c TG)and osteoclastic knockout(Nron CKO)mouse models were generated.When Nron was overexpressed,the orthodontic tooth movement rate was reduced.In addition,the number of osteoclasts decreased,and the activity of osteoclasts was inhibited.Mechanistically,Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation.In contrast,by deleting Nron specifically in osteoclasts,tooth movement speed increased in Nron CKO mice.These results indicate that lnc RNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
文摘Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.
基金This study was supported by the Natural Science Foundation of China(No.81871490,81670958,81670973)Science and Technology Commission of Shanghai Municipality(No.17510710800,19441902900)+2 种基金Two-hundred Talent in Shanghai Jiao Tong University School of Medicine(No.20191819)Program of Shanghai Academic/Technology Research Leader(No.19XD1434500)Ninth People's Hospital affiliated to Shanghai Jiao Tong University,School of Medicine"Multi-Disciplinary Team"Clinical Research Project(No.201701013)。
文摘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 in vitro and in vivo,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 in vivo 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.
文摘The dental operative microscope has been widely employed in the field of dentistry,particularly in endodontics and operative dentistry,resulting in significant advancements in the effectiveness of root canal therapy,endodontic surgery,and dental restoration.However,the improper use of this microscope continues to be common in clinical settings,primarily due to operators’insufficient understanding and proficiency in both the features and established operating procedures of this equipment.In October 2019,Professor Jingping Liang,Vice Chairman of the Society of Cariology and Endodontology,Chinese Stomatological Association,organized a consensus meeting with Chinese experts in endodontics and operative dentistry.The objective of this meeting was to establish a standard operation procedure for the dental operative microscope.Subsequently,a consensus was reached and officially issued.Over the span of about four years,the content of this consensus has been further developed and improved through practical experience.
基金supported by the National Natural Science Foundation of China(No.82001106,81970918,81901043).
文摘Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque.It remains challenges for current practice to specifically identify,intervene and interrupt the development of caries while restoring defects.In this study,inspired by natural dental plaque,a stimuli-responsive multidrug delivery system(PMs@NaF-SAP)has been developed to prevent tooth decay and promote enamel restoration.Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond,followed by conjugation with salivary-acquired peptide(SAP)to endow the nanoparticle with strong adhesion to tooth enamel.The constructed PMs@NaF-SAP specifically adheres to tooth,identifies cariogenic conditions and intelligently releases drugs at acidic pH,thereby providing antibacterial adhesion and cariogenic biofilm resistance,and restoring the microarchitecture and mechanical properties of demineralized teeth.Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues.These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.
基金supported by grants from National Key R&D Programme of China (No. 2022YFC2504200)the Fundamental Research Funds for the Central Universities (No. 2042023kf0154, No. 2042023kfyq02)+1 种基金the National Nature Science Foundation of China (No. 82273306, No.81901016, No. 82303326)Wuhan Knowledge Innovation Program (No.2022020801020469)。
文摘A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.
基金supported by grants from the National Key R&D Program of China(2022YFA1103200)National Natural Science Foundation Projects of China(81822012,82061130222,81771043,92049201,82001070)+1 种基金Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)the Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(8191101676,201409006400)。
文摘In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing self-healing,however,the mechanism is unclear.Using this type of fracture mouse model,we discovered the activation of Hedgehog(Hh)signaling in the injured growth plate,which could activate chondrocytes in growth plate and promote cartilage repair.
基金supported by the National Nature Science Foundations of China(grant numbers 81772275 and 32071462)。
文摘Tongue squamous cell carcinoma is highly malignant and has a poor prognosis.In this study,we aimed to combine whole-genome sequencing,whole-genome methylation,and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better.Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples.After multi-omics sequencing,differentially methylated intervals,methylated loop sites,methylated promoters,and transcripts were screened for variation in all paired samples.Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma.We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels.Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade,which is associated with cancer progression and the development of drug resistance during treatment.The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings.We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs.Collectively,changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.
基金supported by the National Natural Science Foundation of China(82025011,82220108018,82270981,82100975,82201078)the National Key R&D Program of China(2021YFC2400405)+1 种基金the Fundamental Research Funds for the Central Universities(2042023kfyq022042022dx0003).
文摘Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages phenotype.In a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.
基金support by the Natural Science Foundation of China(81871490,81670958,81970973)Science and Technology Commission of Shanghai Municipality(17510710800,17410710500,19441902900)+3 种基金Program of Shanghai Academic/Technology Research Leader(19XD1434500)Pudong New Area Commission of Health and Family Planning(PW2016E1)Double Hundred Plan of Shanghai Jiao Tong University School of Medicine(20191819)Incentive Project of High-level Innovation Team for Shanghai Jiao Tong University School of Medicine。
文摘Personalized precision therapy and rapid osseointegration are the main development directions of dental implants.3 D printing is a vital advanced manufacturing technology for personalized precision therapy.However,the osteogenesis of the 3 D printed Ti6 Al4 V implants is unsatisfactory.From the bionic perspective,the hierarchical micro/nano-topography can mimic the microenvironment of the multilevel structure of natural bone tissue and may endow the implant surface with superior bioactivity.In the present study,the hierarchical micro/nano-topography was successfully fabricated by construction the nanoscale feature on 3 D printed microscale roughness surface of 3 D-printed Ti6 Al4 V implants by alkali-heat treatment and hydrothermal treatment.Then the cell biological responses in vitro and osseointegration performance in vivo were systematically evaluated.The hierarchical micro/nano-topography evidently increased the roughness,improved the hydrophilicity and accelerated the hydroxyapatite deposition and mineralization,which significantly enhanced the adhesion,differentiation and extracellular matrix mineralization of bone marrow derived mesenchymal stromal cells(BMSCs).Most importantly,the hierarchical micro/nano-topography on 3 D-printed implants facilitated the new bone formation and rapid osseointegration in vivo.Our study suggested that 3 D-printed implant with micro/nano-topography may be a promising candidate to be applied in orthopedic field to meet the need of customized therapy and rapid osseointegration.
文摘Periodontitis is a prevalent oral disease. It can cause tooth loss and has a significant impact on patients’ quality of life. While existing treatments can only slow the progression of periodontitis, they are unable to achieve complete regeneration and functional reconstruction of periodontal tissues. As a result, regenerative therapies based on biomaterials have become a focal point of research in the field of periodontology. Despite numerous studies reporting the superiority of new materials in periodontal regeneration, limited progress has been made in translating these findings into clinical practice. This may be due to the lack of appropriate animal models to simulate the tissue defects caused by human periodontitis. This review aims to provide an overview of established animal models for periodontal regeneration, examine their advantages and limitations, and outline the steps for model construction. The objective is to determine the most relevant animal models for periodontal regeneration based on the hypothesis and expected outcomes.
文摘The authors regret that there are errors in the article Fig.8A and Fig.S22A due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading.Although it does not affect the conclusion,these are obvious errors.The authors have now modified as below.The original data of these figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.The authors apologize for any inconvenience caused to the journal and readers.
基金supported by the National Natural Science Foundation of China(Nos.82222035 and 81602489)the Guangdong Basic and Applied Basic Research Foundation(Nos.2021A1515111036 and 2022A1515110308)+1 种基金the Medical Scientific Research Foundation of Guangdong Province of China(No.A2023274)the Basic Research Program of Shenzhen Innovation Council(No.JCYJ20210324105609024)。
文摘As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent sensors.However,the CDs with deep-red(DR)or near-infrared(NIR)emission have rarely been reported.In this work,we prepared deep-red emissive fluorine-doped carbon quantum dots(F-CDs)by introducing a precursor simultaneously containing fluorine and amidogen.The synergistic effect of nitrogen doping and D-π-A pattern production contributed to the maximum emission of F-CDs at 636 nm with an absolute quantum yield of 36.00%±0.68%.Moreover,we designed an F-CDs-based fluorescence assay to determine the content of hypochlorite(ClO^(-)),with a limit of detection(LOD)as low as 15.4 nmol/L,indicating the high sensitivity of F-CDs to ClO^(-).In real samples,the F-CDs-based fluorescent sensor exhibited excellent sensitivity and selectivity in the detection of ClO^(-),with an error below 2%,suggesting their great potential in daily life.In cancer cell imaging,the F-CDs not only demonstrated high sensitivity to ClO^(-)but also exhibited excellent mitochondria targeting,as evidenced by the high Pearson's correlation coefficient(PCC)of 0.93 in colocalization analysis.The work presented here suggests the great potential of replacing commercial dyes with F-CDs for highly specific mitochondria labeling and cell imaging.
基金supported by National Natural Science Foundation of China(Nos.82273202,82072996,82073349)National Key Research and Development Program(No.2022YFC2504200,China)+1 种基金Fundamental Research Funds for the Central Universities(No.2042024kf0021,China)Interdisciplinary Innovative Foundation of Wuhan University(No.XNJC202303,China).
文摘Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid tumors.However,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector function of CAR-T cells,leading to a relapse rate of up to 75%in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies.Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.In this review,we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy.These insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.
基金supported by the Beijing Training Project for the Leading Talents in S&T(Grant No.Z191100006119022)the National Key Program of the National Natural Science Foundation of China(Grant No.51705006)Capital’s Funds for Health Improvement and Research(2022-2Z-4106).
文摘Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects.Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials.Previous studies have mainly focused on innate immune cells such as macrophages.In our previous work,we found that T lymphocytes,as adaptive immune cells,are also essential in the osteoinduction procedure.As the most important antigen-presenting cell,whether dendritic cells(DCs)can recognize non-antigen biomaterials and participate in osteoinduction was still unclear.In this study,we found that surgical trauma associated with materials implantation induces necrocytosis,and this causes the release of high mobility group protein-1(HMGB1),which is adsorbed on the surface of bone substitute materials.Subsequently,HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells,and the inflammatory response was activated.Finally,activated DCs release regeneration-related chemokines,recruit mesenchymal stem cells,and initiate the osteoinduction process.This study sheds light on the immune-regeneration process after bone substitute materials implantation,points out a potential direction for the development of bone substitute materials,and provides guidance for the development of clinical surgical methods.
基金supported by National Natural Science Foundation of China(Grant 81600906)the Fundamental Research Funds for the Central University of China(No.2042018kf0108).
文摘Postmenopausal osteoporosis is a common chronic dynamic bone disorder,caused by estrogen deficiency.To address this issue,we constructed a controlled drug-release system composed of poly(N-isopropylacrylamide)brush modified mesoporous hydroxyapatite(MHA-SIM-P)loaded with simvastatin(SIM)using an ovariectomised(OVX)rat model.Quantitative alkaline phosphatase activity assay,alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro.The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells(BMSCs)in vitro.In osteoporotic animal model,the therapeutic efficiency for bone defect was evaluated byμCT analysis,tartrateresistant acid phosphatase,haematoxylin and eosin staining,which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks.This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis.Thus,this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.
