BACKGROUND:Pearl powder is rich in many active ingredients,which can promote the proliferation and migration of fibroblasts,thus promoting wound healing and skin tissue regeneration.However,the effect of nano-pearl powder water-soluble matrix on proliferation,migration and apoptosis of mouse fibroblasts L929 has not been reported.OBJECTIVE:To investigate the effect of nano-pearl powder water-soluble matrix on the proliferation,migration and apoptosis of mouse fibroblasts L929.METHODS:Passage 6 L929 cells were divided into five groups.The negative control group did not add any material;the positive control group added PBS,and the low,medium and high mass concentration groups of water-soluble matrix were added with 10,25 and 40 μg/mL of nano-pearl powder water-soluble matrix,respectively.The proliferation of L929 cells was detected by MTT assay.The migration ability of L929 cells was detected by Transwell.The apoptosis rate of L929 cells was detected by flow cytometry.The expressions of apoptosis-related proteins Bax,Bcl-2,and Caspase-1 were detected by western blot assay.RESULTS AND CONCLUSION:(1)The results of MTT assay and Transwell chamber experiment showed that the water-soluble matrix of nano-pearl powder could promote the proliferation and migration of L929 cells,and it was concentration dependent.(2)Flow cytometry and western blot assay results showed that the water-soluble matrix of nano-pearl powder could reduce the apoptosis rate of L929 cells and the protein expression of Bax and Caspase-1,and increase the expression of Bcl-2 protein,and it was concentration dependent.(3)These findings exhibited that the water-soluble matrix of nano-pearl powder could inhibit cell apoptosis under high mass concentration treatment.The results show that the water-soluble matrix of nano-pearl powder can promote the proliferation and migration of fibroblasts and inhibit the apoptosis of fibroblasts.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

BACKGROUND:Mineralized collagen is the fundamental unit of bone structure and function and a major component of the extracellular matrix.Biomimetic methods have been developed to fabricate mineralized collagen with a natural bone nanostructure.Currently,mineralized collagen has been approved by regulatory authorities and applied clinically,playing a positive role in bone defect repair.OBJECTIVE:To present the integration strategies of bioactive factors with mineralized collagen,summarize schemes to enhance the osteogenic potential of mineralized collagen,emphasize the multifunctional coordination applications of mineralized collagen,and finally discuss current research focuses and future trends.METHODS:The authors searched for relevant literature in databases such as PubMed,Web of Science,Medline,WanFang,and CNKI,from 2009 to 2023,using keywords"mineralized collagen,biomimetic,functionalization,bioactive factors,osteogenesis,multi-functional coordination,bone tissue repair"in English and"mineralized collagen,biomimetic,functionalization"in Chinese.Out of 375 initially identified articles,57 were included for review after screening.RESULTS AND CONCLUSION:(1)Mineralized collagen,with its porous structure and large surface area,containing nano-hydroxyapatite,makes it an effective carrier for cells,various growth factors,and drugs.(2)Single or multiple bioactive factors can be efficiently and orderly released through different loading methods or combinations,achieving the multifunctionalization of mineralized collagen.The impact of physicochemical conditions on the bioactivity of factors and their effects on the degradability,hydroxylapatite crystal morphology,nanostructure,and content of mineralized collagen should be considered.Moreover,calcium ions in mineralized collagen can be substituted with various inorganic non-metal ions,enhancing its osteogenic,angiogenic,immunomodulatory,and anti-infective properties.(3)Ultimately,during in situ bone regeneration,functionalized mineralized collagen serves as a scaffold material,providing structural support for bone defects,and as a drug delivery system,continuously delivering various bioactive factors locally,playing roles in anti-infection,immunomodulation,promoting angiogenesis and osteogenesis,and repairing various complex bone defects.

BACKGROUND:Dental pulp stem cells,which derived from the dental pulp tissue,are one type of dental-derived mesenchymal stem cells,possess significant properties of self-renewal and multi-lineage differentiation.In recent years,series of researches focus on dental pulp stem cells and their derivatives such as extracellular vesicles,conditioned medium,and decellularized extracellular matrix,those have positive effects on the repair and regeneration of pulp tissue injury,showing an attractive clinical application.OBJECTIVE:To systematically review the researches and applications of dental pulp stem cells and their derivatives in dental pulp tissue engineering.METHODS:Literature searches were conducted in PubMed,China Biology Medicine(CBM),and China National Knowledge Infrastructure(CNKI)databases for articles published from January 2005 to June 2023.The search terms included"dental pulp stem cells,extracellular vesicles,exosomes,apoptotic bodies,conditioned medium,decellularized matrix,regeneration"in Chinese and English.After screening the titles and abstracts,duplicate and irrelevant studies were excluded.Finally,103 studies closely related to dental pulp regeneration were included for review and analysis.RESULTS AND CONCLUSION:Dental pulp stem cells and their derivatives are rich in lots of bioactive factors that can effectively promote odontogenic,angiogenic,and neurogenic differentiation,exhibiting significant potential in the formation of the pulp-dentin complex.However,the clinical translation of dental pulp stem cells and their derivatives still faces several challenges.Future researches should focus on optimizing preparation protocols,elucidating the underlying mechanisms of action,and refining safety assessments to provide novel therapeutic strategies for the repair of dental pulp injury.

BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P＜0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P＜0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P＞0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P＞0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100％.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.

BACKGROUND:Cellular senescence,which triggers the aging process of physiological decline in the body,is closely related to osteoporosis.With the development of aging research,significant progress has been made in the study of targeted clearance of senescent cells.Accordingly,senolytic cell therapy for osteoporosis based on this has attracted increasing attention.Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection.However,existing reviews are mostly based on a single database(such as PubMed)and lack a systematic comparative analysis of Chinese and English literature.Therefore,it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.OBJECTIVE:To summarize the development,current status,hotspots,and future trends of research on aging in the field of osteoporosis over the past 20 years,so as to provide references for future related research.METHODS:We searched for research literature on the correlation between aging and osteoporosis in CNKI,WanFang,VIP and Web of Science Core Database.The search time span was from August 1,2004 to September 24,2024.Then,we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1(Advanced)and Excel(2024)for literature analysis.RESULTS AND CONCLUSION:Since 2004,research on the correlation between aging and osteoporosis has shown a significant growth trend.Bibliometric analysis shows that(as of September 2024),and 1 275 English documents and 151 Chinese documents have been published,with the highest number of publications in China and the United States.In terms of publishing institutions,the Mayo Clinic ranked first,followed by Shanghai Jiao Tong University and the University of California system.As for core authors,Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations,while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature.After the keywords"aging"and"osteoporosis"and their synonyms were excluded,it was found that cellular senescence,senescence-associated secretory phenotype,signaling pathways,and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:Abnormal iron metabolism is closely related to immune inflammatory diseases.Exercise intervention is a potentially effective treatment that can reduce inflammation by regulating iron metabolism and improving immune response.However,how exercise regulates immune system function through iron metabolism still needs to be further explored.OBJECTIVE:To review and summarize the research progress of iron metabolism in immune inflammatory diseases,analyze the regulatory effect of exercise intervention on iron metabolism and the potential mechanism by which exercise regulates immune inflammatory diseases,thereby providing new ideas for the treatment of immune inflammatory diseases in the future.METHODS:The data sources included CNKI and PubMed databases.The retrieval time was from January 2010 to June 2024.The keywords were"iron metabolism,iron homeostasis,hepcidin,immune inflammation,rheumatoid arthritis(RA),inflammatory bowel disease(IBD),multiple sclerosis(MS),systemic lupus erythematosus(SLE),exercise"in Chinese and English,respectively.Finally,101 articles were included for review.RESULTS AND CONCLUSION:(1)Abnormal iron metabolism is closely related to the occurrence and development of a variety of immune inflammatory diseases,such as rheumatoid arthritis,systemic lupus erythematosus,and inflammatory bowel disease.Iron overload or iron deficiency can lead to dysfunction of the immune system,and thereby triggers or aggravates the inflammatory response.(2)Exercise intervention is an important means to regulate iron metabolism.Short-term aerobic exercise or strenuous exercise may lead to short-term iron metabolism disorders.Long-term aerobic exercise can promote the recovery of iron homeostasis.Regular aerobic exercise can reduce serum iron concentration,reduce iron storage in liver and muscle,and improve iron distribution in the body.Long-term exercise can help restore the balance of iron metabolism,thereby reducing the inflammatory response caused by iron metabolism disorders.Exercise types such as strength training and flexibility training also have a significant effect on iron metabolism.The effect of exercise on immune diseases has individual differences.Exercise intensity,duration,frequency and other factors may have different effects on iron metabolism.(3)In general,exercise intervention plays a role in the prevention and treatment of immune inflammatory diseases.However,there are still some limitations in the mechanism elucidation,long-term effects and individual differences in the existing studies.In the future,it is necessary to further explore the specific regulatory mechanism of exercise on iron metabolism and the individualized therapeutic effects of different types of exercise.

BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.