Background:The Taylor Spatial Frame(TSF)has gained popularity among orthopedic surgeons for treating open fractures.However,a key challenge is the timely and safe removal of the frame.This study assessed the efficacy ...Background:The Taylor Spatial Frame(TSF)has gained popularity among orthopedic surgeons for treating open fractures.However,a key challenge is the timely and safe removal of the frame.This study assessed the efficacy and safety of axial load-share ratio(ALSR)testing to evaluate callus healing strength after TSF treatment of open tibial fractures.Methods:A retrospective case-control study was conducted,analyzing 180 adult patients with open tibial fractures treated at Tianjin Hospital’s Orthopedic Limb Correction Unit between August 2019 and August 2022.All patients underwent TSF external fixation surgery,and were divided into two groups based on ALSR testing.Group I(92 patients)underwent ALSR testing,with frame removal if the test value fell below 5%.Traditional methods were used for fixator removal guidance in Group II(88 patients).Clinical outcomes,including fixation duration,complications after fixator removal,and Johner-Wruhs functional scores,were compared between the two groups.Results:The groups showed no statistically significant differences(P>0.05)in sex,age,injury side,body mass index,surgery timing,or fracture type.Group I had a significantly shorter fixation duration(25.85±5.57 weeks)compared to Group II(31.82±6.98 weeks)(P<0.05).Following fixator removal,Group I demonstrated superior Johner-Wruhs scores compared to Group II,indicating better outcomes(P<0.05).Complication rates did not differ significantly between the groups at the last follow-up(P>0.05).Conclusion:Regular postoperative ALSR testing could safely and effectively guide TSF removal following open tibial fracture treatment.This method significantly reduced fixation duration compared to traditional guidance methods while maintaining efficacy and safety.展开更多
The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion r...The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.展开更多
Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing.In this study,we aimed to develop an osteoanabolic therapy which activates the W...Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing.In this study,we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway,a molecular driver of endochondral ossification.We hypothesize that using an mRNAbased therapeutic encodingβ-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes.To optimize a delivery platform built on recent advancements in liposomal technologies,two FDA-approved ionizable phospholipids,DLin-MC3-DMA(MC3)and SM-102,were used to fabricate unique ionizable lipid nanoparticle(LNP)formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model.Using firefly luciferase mRNA as a reporter gene to track and quantify transfection,SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection,minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs.The generatedβ-cateninGOF mRNA encapsulated in SM-102 LNPs(SM-102-β-cateninGOF mRNA)showed bioactivity in vitro through upregulation of downstream canonical Wnt genes,axin2 and runx2.When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model,histomorphometric analysis showed increased bone and decreased cartilage composition with the 45μg concentration at 2 weeks post-fracture.μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo,revealing significantly more bone volume over total volume in the 45μg group.Thus,we generated a novel mRNA-based therapeutic encoding aβ-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.展开更多
This paper describes an experimental study about magnetic stimulation (MS) effects on the fracture healing of 120 fresh fractures and their blood biochemical parameters during their recovery. The mechanism of promotin...This paper describes an experimental study about magnetic stimulation (MS) effects on the fracture healing of 120 fresh fractures and their blood biochemical parameters during their recovery. The mechanism of promoting the recovering process by MS is discussed and analysed. The experiments show that MS can advance calcium deposit on fractured bones and metabolism of calcium and phosphorus, which promote the process of fracture healing.展开更多
Bones are organs of the skeletal system, providing shape, mechanical support, and protection to the body and facilitating the movement. In addition, bones contribute to the mineral homeostasis of the body and have rec...Bones are organs of the skeletal system, providing shape, mechanical support, and protection to the body and facilitating the movement. In addition, bones contribute to the mineral homeostasis of the body and have recently been found to participate in endocrine regulation of energy metabolism. The well-known limitations associated with clinical use of autografts and allografts continue to drive efforts to develop bone graft substitutes, using the principles of biomaterials and tissue engineering. Under some stressful and continuous compressive conditions, the ability of the bone tissue to tolerate strength decreases. Whenever these forces overcome the toleration of the bone tissue, bone fracture occurs. years展开更多
A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured...A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured using standardized methods and left to heal for 3, 7, 14, 21 and 24 d, respectively. The avidin-biotin complex (ABC) method demonstrated an accumulation of positively stained primitive mesenchymal cells at the fracture site in the hematoma stage of bone repair. These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation. Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteoprogenitor cells during fracture healing of the mandible and that BMP may play a significant role in osteogenesis during bone healing.展开更多
Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture he...Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 (Lrp6~/-) and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6~^- mice and wild-type controls (Lrp6~/~). Fractures were analyzed using micro-computed tomography (~CT) scans, biomechanical testing, and histological analysis. Lrp6~/- mice had significantly decreased stiffness and strength at 28 days post fracture (PF) and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.展开更多
In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is ...In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.展开更多
BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs f...BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.展开更多
A first order system model is proposed for simulating the influence of stress stimulation on fracture strength during fracture healing. To validate the model, the diaphyses of bilateral tibiae in 70 New Zealand rabbit...A first order system model is proposed for simulating the influence of stress stimulation on fracture strength during fracture healing. To validate the model, the diaphyses of bilateral tibiae in 70 New Zealand rabbits were osteotomized and fixed with rigid plates and stress-relaxation plates, respectively. Stress shielding rate and ultimate bending strength of the healing bone were measured at 2 to 48 weeks postoperatively. Ratios of stress stimulation and fracture strength of the healing bone to those of intact bone were taken as the system input and output. The assumed first order system model can approximate the experimental data on fracture strength from the input of stress stimulation over time, both for the rigid plate group and the stress-relaxation plate group, with different system parameters of time constant and gain. The fitting curve indicates that the effect of mechanical stimulus occurs mainly in late stages of healing. First order system can model the stress adaptation process of fracture healing. This approach presents a simple bio-mathematical model of the relationship between stress stimulation and fracture strength, and has the potential to optimize planning of functional exercises and conduct parametric studies.展开更多
Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction ...Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.展开更多
Summary: In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a...Summary: In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a transverse transcondylar osteotomy of the distal femur were fixed in- tramedullary by a HA/PDLLA rod (4. 5 mm in diameter, 30-40 mm in length). The follow-up time lasted 1, 2, 4, 6 and 12 week(s). Roentgenographic, histological and ultrastructural analyses were conducted. The results showed that all osteotomies united within 6 weeks without delay. No accumulation of inflammatory cells was seen. Ultrastructural studies showed that polymorphonuclear neutrophils and macrophages were observed mainly at the 1st week, but only few were noted at the 2nd week. The inflammatory and debridement stages were not prolonged. Large amount of active fibroblasts and some chondroblasts were observed at the 2nd week, suggesting a fibrous callus stage. The main cellularity at 4th week was osteoblasts and osteocytes. Part of osteocytes had already entered the static stage at the 6th week. Our experiment showed that the HA/PDLLA had good biocompatibility, sufficient mechanical strength and caused no delay to the fracture healing.展开更多
There is a tendency to treat humeral fractures with the use of splintage in resource poor countries due to a perceived high rate of complications with operative fixation. The Surgical Implant Generation Network (SIGN)...There is a tendency to treat humeral fractures with the use of splintage in resource poor countries due to a perceived high rate of complications with operative fixation. The Surgical Implant Generation Network (SIGN) intra medullary nail has provided an alternative in the management of humeral shaft fractures. Due to the paucity of research work in this area, our study evaluated factors that influence the time to fracture union in humeral shaft fractures. Fifty-eight humeral Diaphysial fractures were treated over six years. It is a retrospective study. Case notes and the database were analysed. The statistical analysis was done using the SPSS 24 software. The time to fracture healing was the primary outcome variable and how it was influenced by patient and implant variables was studied. The mean time to fracture healing was 17.38 weeks. All 58 fractures united. The mean time to fracture healing in the 20 - 29 years was 16.00 weeks which was lower than in older age groups. Fractures in males healed at 16.33 weeks and in females at 18.76 weeks. Patients with Diabetes Mellitus had a mean healing time of 29.00 weeks, while third proximal fractures healed in a mean time of 15.25 weeks. Age and sex had no significant influence on the time to fracture healing while Diabetes Mellitus, longer duration of antibiotic use, open fractures, and presence of fracture gap post fixation and third middle fractures had increased time to fracture healing.展开更多
AIM: To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS: The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and...AIM: To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS: The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and bone healing in key electronic data bases from 1980 onwards using the terms vitamin D and bone healing, callus, fracture healing. All data were examined carefully and categorized according to type of study. A summary of the diverse terms and approaches employed in the research, as well as the rationale for hypothesizing vitamin D has a role in fracture healing was detailed.RESULTS: The results show very few human studies have been conducted to examine if vitamin D is effective at promoting post fracture healing, and the different ani-mal models that have been studied provide no consensus on this topic. The terms used in the related literature, as well as the methods used to arrive at conclusions on this clinical issue are highly diverse, there is no standardization of either of these important terms and methodolo-gies, hence no conclusive statements or clinical guide-lines can be forthcoming. There is a strong rational for continuing to examine if vitamin D supplements should be administered post-fracture, and ample evidence vitamin D is an essential hormone for functioning in general, as well as bone health and muscle as this relates to bone density.CONCLUSION: Whether those with low vitamin D levels can beneft from supplements if their nutritional practices do not cover recommended daily amounts, remains in question.展开更多
Objective:To study the effects of Shang Ke Jie Gu tablet on fracture healing in rabbits.Methods:40 New Zealand rabbits,half male and half female,were randomly divided into two groups:normal saline group(N group)and Sh...Objective:To study the effects of Shang Ke Jie Gu tablet on fracture healing in rabbits.Methods:40 New Zealand rabbits,half male and half female,were randomly divided into two groups:normal saline group(N group)and Shang Ke Jie Gu tablet group(S group).Each group consisted of 20 rabbits.Left radial fracture models in upper and middle sections were made in rabbits and then intra-gastric administration was given.Five rabbits in each group were killed on the 10 th,20^(th),30^(th) and 40^(th) day after surgery,left radius was taken to get an X-ray.The degree of healing was assessed by the evaluation criteria of Shanghai Orthopaedics Institute.Results:The degree of fracture healing in S group was higher in the comparison with that in N group.Conclusions:Shang Ke Jie Gu tablet might affect endochondral ossification during fracture healing of rabbits,and promote porosis and fracture healing.展开更多
[Objectives]To compare the fracture healing of keeping lateral pterygoid muscle anatomic reduction(simulated manipulation fracture reduction)with condylar free reduction in the treatment of condylar fractures.[Methods...[Objectives]To compare the fracture healing of keeping lateral pterygoid muscle anatomic reduction(simulated manipulation fracture reduction)with condylar free reduction in the treatment of condylar fractures.[Methods]Twenty-four New Zealand rabbits were randomly divided into two groups to mandibular condylar neck fracture model was established.one team keep the lateral pterygoid muscle,the other excise it.Cervical vascular perfusion was done with ink before animals executed after operation 2,4,6 and 8 weeks.Bilateral anteroposterior and mediolateral condylar diameters measured.Changes of operation side condylar proliferating layer,microvessel number and bone parameters were observed and analyzed after slices and HE staining.[Results]The mediolateral condylar diameters of operation side were significantly smaller than health side in condylar free reduction group at the 4,6,8 weeks(P<0.05),but there was no statistical difference in the anteroposterior condylar diameters at each time point(P>0.05).There were no significant differences in the anteroposterior and mediolateral condylar diameters of the anatomic reduction lateral pterygoid muscle group compared between the operation side and health side(P>0.05).The number of microvessel in condylar free reduction group were smaller than those in anatomic reduction lateral pterygoid muscle group(P<0.05).There were significant differences in BV/TV,Tb.Th,Tb.Sp between the condylar free reduction group and the anatomic reduction lateral pterygoid muscle group(all P<0.05),and the Tb.N were significantly differences between two groups at the 4,6,8 weeks(P<0.05).[Conclusions]When the condyle is fractured it should keep lateral pterygoid muscle(manipulation fracture reduction)as possible,which is important in the fracture healing and functional recovering of mandibular.展开更多
To investigate the impact of different kinds of nerve injuries of early-stage fracture healing.Methods Three groups of rats were included in the experiment among which group 1 was inflicted with femoral fracture and T...To investigate the impact of different kinds of nerve injuries of early-stage fracture healing.Methods Three groups of rats were included in the experiment among which group 1 was inflicted with femoral fracture and T10 spinal cord transsection (SCI),group 2 was inflicted with femoral and peripheral nerve resection (PNR),and group 3 with simple femoral fracture as control group.Two weeks after operation the femoral bones were collected for X-ray checking and 2 more weeks later X-ray checking was performed again followed by pathomorphologic exams.Results X-ray result showed no massive calluses in the bones in the 2nd week postoperatively,while in the 4th week,callus appeared with larger size in group 3 than that of group 1 and with smaller size than that of group 2.It was the same with the result of pathomorphologic examining.Cortical bone bridges between fracture point and osteiod were also found in group 2 and there were less normal blood vessels and worse bone remodeling than that of group 3.There were relatively immature calluses with more fibroblast-like cells and disordered bone structure in group 2.Group 3 showed normal healing process and callus structure.Conclusion Early-stage bone fracture healing can be influenced significantly by different kinds of nerve injuries.6 refs,6 figs.展开更多
The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture hea...The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture healing(e.g.,metallic and composite materials),they cannot fulfill the requirements due to the slow degradation rate,limited osteogenic activity,inadequate osseointegration ability,and suboptimal mechanical properties.Since early 2000,nanomaterials successfully mimic the nanoscale features of bones and offer unique properties,receiving extensive attention.This paper reviews the achievements of nanomaterials in treating bone fracture(e.g.,the intrinsic properties of nanomaterials,nanomaterials for bone defect filling,and nanoscale drug delivery systems in treating fracture delayed union).Furthermore,we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.展开更多
Regulatory T cells(Tregs)suppress immune responses and inflammation.Here,we described the distinct nonimmunological role of Tregs in fracture healing.The recruitment from the circulation pool,peripheral induction,and ...Regulatory T cells(Tregs)suppress immune responses and inflammation.Here,we described the distinct nonimmunological role of Tregs in fracture healing.The recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured bone.The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs.Punctual depletion of Tregs compromised the fracture healing process,which leads to increased bone nonunion.In addition,bone callus Tregs showed unique T-cell receptor repertoires.Amphiregulin was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways.The results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction.Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells.Our findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.展开更多
As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients’ physical and ps...As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients’ physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine(TCM). In the early stage of fracture healing,the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α(HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms,in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.展开更多
基金funding support from Natural Science Foundation Key Project of Tianjin(20JCZDJC00600)Tianjin Health Research Project(TJWJ2023QN050)+2 种基金Applied Basic Research Foundation of Tianjin(22JCQNJC00230,22JCQNJC00360)Beijing-Tianjin-Hebei Basic Research Cooperation Project(J230007/23JCZXJC00050)Tianjin Municipal Health Commission Key Discipline Specialization(TJWJ2024XK015).
文摘Background:The Taylor Spatial Frame(TSF)has gained popularity among orthopedic surgeons for treating open fractures.However,a key challenge is the timely and safe removal of the frame.This study assessed the efficacy and safety of axial load-share ratio(ALSR)testing to evaluate callus healing strength after TSF treatment of open tibial fractures.Methods:A retrospective case-control study was conducted,analyzing 180 adult patients with open tibial fractures treated at Tianjin Hospital’s Orthopedic Limb Correction Unit between August 2019 and August 2022.All patients underwent TSF external fixation surgery,and were divided into two groups based on ALSR testing.Group I(92 patients)underwent ALSR testing,with frame removal if the test value fell below 5%.Traditional methods were used for fixator removal guidance in Group II(88 patients).Clinical outcomes,including fixation duration,complications after fixator removal,and Johner-Wruhs functional scores,were compared between the two groups.Results:The groups showed no statistically significant differences(P>0.05)in sex,age,injury side,body mass index,surgery timing,or fracture type.Group I had a significantly shorter fixation duration(25.85±5.57 weeks)compared to Group II(31.82±6.98 weeks)(P<0.05).Following fixator removal,Group I demonstrated superior Johner-Wruhs scores compared to Group II,indicating better outcomes(P<0.05).Complication rates did not differ significantly between the groups at the last follow-up(P>0.05).Conclusion:Regular postoperative ALSR testing could safely and effectively guide TSF removal following open tibial fracture treatment.This method significantly reduced fixation duration compared to traditional guidance methods while maintaining efficacy and safety.
基金This work was supported by the National Natural Science Foundation of China(Nos.81972058,81902194 and 82202680)the Science and Technology Commission of Shanghai Municipality(No.22YF1422900)+3 种基金the Shanghai Municipal Key Clinical Specialty,China(No.shslczdzk06701)the National Facility for Translational Medicine(Shanghai),China(No.TMSZ-2020-207)the Shanghai Engineering Research Center of Orthopedic Innovative Instruments and Personalized Medicine Instruments and Personalized Medicine(No.19DZ2250200)the Key R&D Program of Ningxia,China(Nos.2020BCH01001 and 2021BEG02037).
文摘The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.
基金supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)of the National Institutes of Health(NIH)under award number R01 AR077761support from the Musculoskeletal Regeneration Partnership Fund by Mary Sue and Michael Shannon and by Project Number 20-166 from the Orthoregeneration Network for Kick-Starter Grantsupported by the National Institute on Aging of the National Institutes of Health under Award Number F30AG077748 and the University of Wisconsin-Madison Medical Scientist Training Program:T32GM140935.All content is solely the responsibility of the authors and does not represent the official views of National Institutes of Health,Orthoregeneration Network or Shannon Foundation.
文摘Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing.In this study,we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway,a molecular driver of endochondral ossification.We hypothesize that using an mRNAbased therapeutic encodingβ-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes.To optimize a delivery platform built on recent advancements in liposomal technologies,two FDA-approved ionizable phospholipids,DLin-MC3-DMA(MC3)and SM-102,were used to fabricate unique ionizable lipid nanoparticle(LNP)formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model.Using firefly luciferase mRNA as a reporter gene to track and quantify transfection,SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection,minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs.The generatedβ-cateninGOF mRNA encapsulated in SM-102 LNPs(SM-102-β-cateninGOF mRNA)showed bioactivity in vitro through upregulation of downstream canonical Wnt genes,axin2 and runx2.When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model,histomorphometric analysis showed increased bone and decreased cartilage composition with the 45μg concentration at 2 weeks post-fracture.μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo,revealing significantly more bone volume over total volume in the 45μg group.Thus,we generated a novel mRNA-based therapeutic encoding aβ-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.
文摘This paper describes an experimental study about magnetic stimulation (MS) effects on the fracture healing of 120 fresh fractures and their blood biochemical parameters during their recovery. The mechanism of promoting the recovering process by MS is discussed and analysed. The experiments show that MS can advance calcium deposit on fractured bones and metabolism of calcium and phosphorus, which promote the process of fracture healing.
文摘Bones are organs of the skeletal system, providing shape, mechanical support, and protection to the body and facilitating the movement. In addition, bones contribute to the mineral homeostasis of the body and have recently been found to participate in endocrine regulation of energy metabolism. The well-known limitations associated with clinical use of autografts and allografts continue to drive efforts to develop bone graft substitutes, using the principles of biomaterials and tissue engineering. Under some stressful and continuous compressive conditions, the ability of the bone tissue to tolerate strength decreases. Whenever these forces overcome the toleration of the bone tissue, bone fracture occurs. years
文摘A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein(BMP) in experimental fracture healing. Rabbit mandibles were fractured using standardized methods and left to heal for 3, 7, 14, 21 and 24 d, respectively. The avidin-biotin complex (ABC) method demonstrated an accumulation of positively stained primitive mesenchymal cells at the fracture site in the hematoma stage of bone repair. These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation. Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteoprogenitor cells during fracture healing of the mandible and that BMP may play a significant role in osteogenesis during bone healing.
基金Grand Rapids Area Pre-College Engineering Programsupported by NIH grant AR053293
文摘Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 (Lrp6~/-) and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6~^- mice and wild-type controls (Lrp6~/~). Fractures were analyzed using micro-computed tomography (~CT) scans, biomechanical testing, and histological analysis. Lrp6~/- mice had significantly decreased stiffness and strength at 28 days post fracture (PF) and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.
基金Supported by German Research Foundation(DFG)focusing on“Interplay between mononuclear and osteogenic cells during fracture healing in type 2 diabetics”,No.EH 471/2(to Ehnert S)German Research Foundation within the context of the Collaborative Research Center(CRC)1149“Danger Response,Disturbance Factors and Regenerative Potential after Acute Trauma”,No.251293561,C01(to Ignatius A and Fischer V)+1 种基金DFG in context of the CRC 1149,No.251293561,A01 and No.251293561 Z02(to Huber-Lang M)and DFG in the context of the CRC 1149,No.251293561,C07(to Kalbitz M).
文摘In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.
基金the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea,No.HI20C1405。
文摘BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.
基金Project (No. 39470698) supported by the National Natural Science Foundation of China
文摘A first order system model is proposed for simulating the influence of stress stimulation on fracture strength during fracture healing. To validate the model, the diaphyses of bilateral tibiae in 70 New Zealand rabbits were osteotomized and fixed with rigid plates and stress-relaxation plates, respectively. Stress shielding rate and ultimate bending strength of the healing bone were measured at 2 to 48 weeks postoperatively. Ratios of stress stimulation and fracture strength of the healing bone to those of intact bone were taken as the system input and output. The assumed first order system model can approximate the experimental data on fracture strength from the input of stress stimulation over time, both for the rigid plate group and the stress-relaxation plate group, with different system parameters of time constant and gain. The fitting curve indicates that the effect of mechanical stimulus occurs mainly in late stages of healing. First order system can model the stress adaptation process of fracture healing. This approach presents a simple bio-mathematical model of the relationship between stress stimulation and fracture strength, and has the potential to optimize planning of functional exercises and conduct parametric studies.
基金This work was supported by the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2021MS407).
文摘Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.
基金This project was supported by the National Natural Science Foundation of China !(No. 969202011 ) by Hubei Province Natural S
文摘Summary: In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a transverse transcondylar osteotomy of the distal femur were fixed in- tramedullary by a HA/PDLLA rod (4. 5 mm in diameter, 30-40 mm in length). The follow-up time lasted 1, 2, 4, 6 and 12 week(s). Roentgenographic, histological and ultrastructural analyses were conducted. The results showed that all osteotomies united within 6 weeks without delay. No accumulation of inflammatory cells was seen. Ultrastructural studies showed that polymorphonuclear neutrophils and macrophages were observed mainly at the 1st week, but only few were noted at the 2nd week. The inflammatory and debridement stages were not prolonged. Large amount of active fibroblasts and some chondroblasts were observed at the 2nd week, suggesting a fibrous callus stage. The main cellularity at 4th week was osteoblasts and osteocytes. Part of osteocytes had already entered the static stage at the 6th week. Our experiment showed that the HA/PDLLA had good biocompatibility, sufficient mechanical strength and caused no delay to the fracture healing.
文摘There is a tendency to treat humeral fractures with the use of splintage in resource poor countries due to a perceived high rate of complications with operative fixation. The Surgical Implant Generation Network (SIGN) intra medullary nail has provided an alternative in the management of humeral shaft fractures. Due to the paucity of research work in this area, our study evaluated factors that influence the time to fracture union in humeral shaft fractures. Fifty-eight humeral Diaphysial fractures were treated over six years. It is a retrospective study. Case notes and the database were analysed. The statistical analysis was done using the SPSS 24 software. The time to fracture healing was the primary outcome variable and how it was influenced by patient and implant variables was studied. The mean time to fracture healing was 17.38 weeks. All 58 fractures united. The mean time to fracture healing in the 20 - 29 years was 16.00 weeks which was lower than in older age groups. Fractures in males healed at 16.33 weeks and in females at 18.76 weeks. Patients with Diabetes Mellitus had a mean healing time of 29.00 weeks, while third proximal fractures healed in a mean time of 15.25 weeks. Age and sex had no significant influence on the time to fracture healing while Diabetes Mellitus, longer duration of antibiotic use, open fractures, and presence of fracture gap post fixation and third middle fractures had increased time to fracture healing.
文摘AIM: To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS: The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and bone healing in key electronic data bases from 1980 onwards using the terms vitamin D and bone healing, callus, fracture healing. All data were examined carefully and categorized according to type of study. A summary of the diverse terms and approaches employed in the research, as well as the rationale for hypothesizing vitamin D has a role in fracture healing was detailed.RESULTS: The results show very few human studies have been conducted to examine if vitamin D is effective at promoting post fracture healing, and the different ani-mal models that have been studied provide no consensus on this topic. The terms used in the related literature, as well as the methods used to arrive at conclusions on this clinical issue are highly diverse, there is no standardization of either of these important terms and methodolo-gies, hence no conclusive statements or clinical guide-lines can be forthcoming. There is a strong rational for continuing to examine if vitamin D supplements should be administered post-fracture, and ample evidence vitamin D is an essential hormone for functioning in general, as well as bone health and muscle as this relates to bone density.CONCLUSION: Whether those with low vitamin D levels can beneft from supplements if their nutritional practices do not cover recommended daily amounts, remains in question.
文摘Objective:To study the effects of Shang Ke Jie Gu tablet on fracture healing in rabbits.Methods:40 New Zealand rabbits,half male and half female,were randomly divided into two groups:normal saline group(N group)and Shang Ke Jie Gu tablet group(S group).Each group consisted of 20 rabbits.Left radial fracture models in upper and middle sections were made in rabbits and then intra-gastric administration was given.Five rabbits in each group were killed on the 10 th,20^(th),30^(th) and 40^(th) day after surgery,left radius was taken to get an X-ray.The degree of healing was assessed by the evaluation criteria of Shanghai Orthopaedics Institute.Results:The degree of fracture healing in S group was higher in the comparison with that in N group.Conclusions:Shang Ke Jie Gu tablet might affect endochondral ossification during fracture healing of rabbits,and promote porosis and fracture healing.
基金Supported by The 28 th batch of science and technology development plan(Medical and Health Science and Technology innovation)project of Suzhou in 2022(SKY2022058)The Ninth Batch of Suzhou Gusu Health Key Talents Project(GSWS2022107)+1 种基金Key Laboratory of Bone Injury of Traditional Chinese Medicine(JSDW202253,SZS2022019)Suzhou Science and Technology Bureau Science and Technology Development Plan(Agricultural Science and Technology Innovation)Project(SNG2020063).
文摘[Objectives]To compare the fracture healing of keeping lateral pterygoid muscle anatomic reduction(simulated manipulation fracture reduction)with condylar free reduction in the treatment of condylar fractures.[Methods]Twenty-four New Zealand rabbits were randomly divided into two groups to mandibular condylar neck fracture model was established.one team keep the lateral pterygoid muscle,the other excise it.Cervical vascular perfusion was done with ink before animals executed after operation 2,4,6 and 8 weeks.Bilateral anteroposterior and mediolateral condylar diameters measured.Changes of operation side condylar proliferating layer,microvessel number and bone parameters were observed and analyzed after slices and HE staining.[Results]The mediolateral condylar diameters of operation side were significantly smaller than health side in condylar free reduction group at the 4,6,8 weeks(P<0.05),but there was no statistical difference in the anteroposterior condylar diameters at each time point(P>0.05).There were no significant differences in the anteroposterior and mediolateral condylar diameters of the anatomic reduction lateral pterygoid muscle group compared between the operation side and health side(P>0.05).The number of microvessel in condylar free reduction group were smaller than those in anatomic reduction lateral pterygoid muscle group(P<0.05).There were significant differences in BV/TV,Tb.Th,Tb.Sp between the condylar free reduction group and the anatomic reduction lateral pterygoid muscle group(all P<0.05),and the Tb.N were significantly differences between two groups at the 4,6,8 weeks(P<0.05).[Conclusions]When the condyle is fractured it should keep lateral pterygoid muscle(manipulation fracture reduction)as possible,which is important in the fracture healing and functional recovering of mandibular.
文摘To investigate the impact of different kinds of nerve injuries of early-stage fracture healing.Methods Three groups of rats were included in the experiment among which group 1 was inflicted with femoral fracture and T10 spinal cord transsection (SCI),group 2 was inflicted with femoral and peripheral nerve resection (PNR),and group 3 with simple femoral fracture as control group.Two weeks after operation the femoral bones were collected for X-ray checking and 2 more weeks later X-ray checking was performed again followed by pathomorphologic exams.Results X-ray result showed no massive calluses in the bones in the 2nd week postoperatively,while in the 4th week,callus appeared with larger size in group 3 than that of group 1 and with smaller size than that of group 2.It was the same with the result of pathomorphologic examining.Cortical bone bridges between fracture point and osteiod were also found in group 2 and there were less normal blood vessels and worse bone remodeling than that of group 3.There were relatively immature calluses with more fibroblast-like cells and disordered bone structure in group 2.Group 3 showed normal healing process and callus structure.Conclusion Early-stage bone fracture healing can be influenced significantly by different kinds of nerve injuries.6 refs,6 figs.
基金the financial support from the Postdoctoral Fund of Hebei Medical University,Key Supported Projects of the Joint Fund of the National Natural Science Foundation of China(Grant No.U22A20357)National Key R&D Program of China(Grant No.2020YFC1107601)+1 种基金Chunyu Project Outstanding Youth Fund of Hebei Medical University(No.CYYQ2023004)the China Postdoctoral Science Foundation(No.2023M730914 and 2023TQ0103).
文摘The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture healing(e.g.,metallic and composite materials),they cannot fulfill the requirements due to the slow degradation rate,limited osteogenic activity,inadequate osseointegration ability,and suboptimal mechanical properties.Since early 2000,nanomaterials successfully mimic the nanoscale features of bones and offer unique properties,receiving extensive attention.This paper reviews the achievements of nanomaterials in treating bone fracture(e.g.,the intrinsic properties of nanomaterials,nanomaterials for bone defect filling,and nanoscale drug delivery systems in treating fracture delayed union).Furthermore,we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.
基金supported by the National Natural Science Foundation of China(Nos.82274026 and 81901884).
文摘Regulatory T cells(Tregs)suppress immune responses and inflammation.Here,we described the distinct nonimmunological role of Tregs in fracture healing.The recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured bone.The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs.Punctual depletion of Tregs compromised the fracture healing process,which leads to increased bone nonunion.In addition,bone callus Tregs showed unique T-cell receptor repertoires.Amphiregulin was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways.The results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction.Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells.Our findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.
基金This work is financially supported by National Natural Science Foundation of China(No.82060877,82104527)the Science and Technology Planning Project of Tibet Autonomous Region(No.XZ202101ZD 0022G)Fundamental Research Funds for the Central Universities(No.lzujbky-2022-ct03).
文摘As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients’ physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine(TCM). In the early stage of fracture healing,the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α(HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms,in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.