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
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
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
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
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
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
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
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
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
Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing.Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes,...Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing.Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes,which respectively exhibit pro-inflammatory or anti-inflammatory functions.Therefore,modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing.Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity.In this study,we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures.The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages,thereby accelerating diabetic fracture healing.We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway.Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.展开更多
OBJECTIVE: To investigate the effect of acupuncture therapy on fracture healing in rats with femur fractures.METHODS: A total of 10 groups were formed;control group, groups sacrificed on 7 th, 14 th, and 21 st days of...OBJECTIVE: To investigate the effect of acupuncture therapy on fracture healing in rats with femur fractures.METHODS: A total of 10 groups were formed;control group, groups sacrificed on 7 th, 14 th, and 21 st days of fracture formation, groups to which acupuncture was applied for 7, 14, and 21 d, groups to which fracture and acupuncture were applied for 7,14, and 21 d. A transverse fracture line was formed in femurs of rats by using a Gigli saw. The Kirschner wire was driven retrograde down from the fracture line to proximal part of the bone and then, the fracture was fixed towards distal part. Acupuncture was applied to the rats for 7, 14, and 21 d as 4 sessions per week after formation of the fracture.RESULTS: Malondialdehyde(MDA), reduced glutathione(GSH) levels, catalase(CAT), glutathione-Stransferase(GST), superoxide dismutase(SOD), and glucose-6-phosphate dehydrogenase(G6 PD) activities were measured. Despite the increased MDA levels, G6 PD and SOD activities reduced during the fracture healing. There was a statistically significant increase in MDA, GSH levels, and G6 PD activity in fracture groups compared to control group, but CAT, GST, and SOD activities decreased. The use of acupuncture enhanced callus development and bone mineralization during bone healing.CONCLUSION: The acupuncture therapy can affect suppression of the effects of free oxygen radicals and regulation of the antioxidant enzyme activity in fracture healing. Thus, it is suggested that acupuncture treatment would be beneficial for fracture healing in order to eliminate the negative effects induced by oxygen free radicals.展开更多
OBJECTIVE:To investigate the efficacy on the combination of oral strontium ranelate(Sr R)with a topical Chinese herbal paste on facilitation of fracture healing.METHODS:An open fracture was created at the mid-shaft of...OBJECTIVE:To investigate the efficacy on the combination of oral strontium ranelate(Sr R)with a topical Chinese herbal paste on facilitation of fracture healing.METHODS:An open fracture was created at the mid-shaft of the right tibia of rat.A herbal pastecalled CDR containing Honghua(Flos Carthami),Chuanxuduan(Radix Dipsaci Asperoidis)and Dahuang(Radix Et Rhizoma Rhei Palmati)was prepared.The rats were treated with either CDR topically on the fracture site,or Sr R orally,or their combinations.Bone turnover biochemical markers in serum were measured.Microarchitecture of the fracture was analyzed using micro-CT after 14 and 28 d,followed by histomorphometrical analysis.RESULTS:Micro-computed tomography analysis revealed that the combined treatment of CDR with600 mg/g Sr R significantly increased the total callus density,mineralized callus volume fraction,mineralized callus mineral content and mineralized callus density of the callus after 28 d of treatment.This result was consistent with the histomorphometrical analysis on the osteoid volume.Analysis of biochemical markers showed that the combined treatments reduced the bone resorption that occurs temporarily after fracture.CONCLUSION:This study demonstrated that the combined treatment of oral Sr R and topical CDR is effective to promote fracture healing by their additive effect on promoting bone formation and retarding bone resorption.展开更多
A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage....A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.展开更多
Objective: To explore the effect of fluvastatin on vascular endothelial growth factor (VEGF) in rats with osteoporosis in the process of fracture healing.Methods: Fractures at the intermediate piece of the femur were ...Objective: To explore the effect of fluvastatin on vascular endothelial growth factor (VEGF) in rats with osteoporosis in the process of fracture healing.Methods: Fractures at the intermediate piece of the femur were made on 72 Sprague Dawley (SD) rats (weighing initially 290-340 g and aged 6 months ) with osteoporosis after ovariectomy for three months, then these rats were divided randomly into the medication administration group (the experimental group ) and the control group, 36 rats each. In the experimental group, the rats received fluvastatin lavage (10 mg/kg per day) since the next day of operation lasting for 6 weeks, and the rats in the control group received placebo. Then the expression of VEGF and VEGF mRNA in bony callus of the two groups was measured respectively with immunohistochemistry and in situ hybridization on days of 3rd, 7th, 14th, 21st, 28th, and 42nd, and image analysis was made with real-color image analysis machine.Results: No difference was found in the cellular localization of VEGF and VEGF mRNA gene expression between the experimental group and the control group in process of fracture healing and their expression modes were almost similar. On the 14th day postoperatively, the positive extent of positive cells in the experimental group was higher than that of the control group (P < 0.05).Conclusion: Fluvastatin can promote the VEGF level in rats with osteoporosis in process of fracture healing.展开更多
Fracture healing progress monitoring techniques attract global research attention due to the importance of selecting the timing of removing the fixation device.To this end,in this research,we present a piezoelectric-b...Fracture healing progress monitoring techniques attract global research attention due to the importance of selecting the timing of removing the fixation device.To this end,in this research,we present a piezoelectric-based smart internal fixation device,in which a piezoelectric sandwich structure is laminated to the surface of a bone plate.In the content,we explain the reasons for utilizing piezoelectric films,elaborate the mechanism of fracture monitoring,and introduce the mechanical parameters of the sensor.The simulation and experimental results show that the electrical output of the device is associated with the elastic modulus of the filler between the tested broken bones when the working load is maintained,indicating that the bone recovery progress could be successfully detected by the developed technique.展开更多
The multifaceted sequence of events that follow fracture repair can be further complicated when considering risk factors for impaired union,present in a large and growing percentage of the population.Risk factors such...The multifaceted sequence of events that follow fracture repair can be further complicated when considering risk factors for impaired union,present in a large and growing percentage of the population.Risk factors such as diabetes,substance abuse,and poor nutrition affect both the young and old,and have been shown to dramatically impair the body’s natural healing processes.To this end,biotherapeutic interventions such as ultrasound,electrical simulation,growth factor treatment(BMP-2,BMP-7,PDGF-BB,FGF-2)have been evaluated in preclinical models and in some cases are used widely for patients with established non-union or risk/indication or impaired healing(i.e.ultrasound,BMP-2,etc.).Despite the promise of these interventions,they have been shown to be reliant on patient compliance and can produce adverse side effects such as heterotopic ossification.Gene and cell therapy approaches have attempted to apply controlled regimens of these factors and have produced promising results.However,there are safety and efficacy concerns that may limit the translation of these approaches.In addition,none of the above mentioned approaches consider genetic variation between individual patients.Several clinical and preclinical studies have demonstrated a genetic component to fracture repair and that SNPs and genetic background variation play major roles in the determination of healing outcomes.Despite this,there is a need for preclinical data to dissect the mechanism underlying the influence of specific gene loci on the processes of fracture healing,which will be paramount in the future of patient-centered interventions for fracture repair.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
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.
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
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.
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.
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supported by the Integrated Project of Major Research Plan of National Natural Science Foundation of China(92249303)Key Project of the National Natural Science Foundation of China(82230071)National Natural Science Foundation of China(32101084,82202344).
文摘Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing.Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes,which respectively exhibit pro-inflammatory or anti-inflammatory functions.Therefore,modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing.Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity.In this study,we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures.The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages,thereby accelerating diabetic fracture healing.We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway.Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.
基金Supported by a Grant from the Firat University Scientific Research Projects Coordination Unit Subject(No.VF.12.12)。
文摘OBJECTIVE: To investigate the effect of acupuncture therapy on fracture healing in rats with femur fractures.METHODS: A total of 10 groups were formed;control group, groups sacrificed on 7 th, 14 th, and 21 st days of fracture formation, groups to which acupuncture was applied for 7, 14, and 21 d, groups to which fracture and acupuncture were applied for 7,14, and 21 d. A transverse fracture line was formed in femurs of rats by using a Gigli saw. The Kirschner wire was driven retrograde down from the fracture line to proximal part of the bone and then, the fracture was fixed towards distal part. Acupuncture was applied to the rats for 7, 14, and 21 d as 4 sessions per week after formation of the fracture.RESULTS: Malondialdehyde(MDA), reduced glutathione(GSH) levels, catalase(CAT), glutathione-Stransferase(GST), superoxide dismutase(SOD), and glucose-6-phosphate dehydrogenase(G6 PD) activities were measured. Despite the increased MDA levels, G6 PD and SOD activities reduced during the fracture healing. There was a statistically significant increase in MDA, GSH levels, and G6 PD activity in fracture groups compared to control group, but CAT, GST, and SOD activities decreased. The use of acupuncture enhanced callus development and bone mineralization during bone healing.CONCLUSION: The acupuncture therapy can affect suppression of the effects of free oxygen radicals and regulation of the antioxidant enzyme activity in fracture healing. Thus, it is suggested that acupuncture treatment would be beneficial for fracture healing in order to eliminate the negative effects induced by oxygen free radicals.
基金Supported by the Health and Medical Research Fund of the Hong Kong Government(Ref:12130581)
文摘OBJECTIVE:To investigate the efficacy on the combination of oral strontium ranelate(Sr R)with a topical Chinese herbal paste on facilitation of fracture healing.METHODS:An open fracture was created at the mid-shaft of the right tibia of rat.A herbal pastecalled CDR containing Honghua(Flos Carthami),Chuanxuduan(Radix Dipsaci Asperoidis)and Dahuang(Radix Et Rhizoma Rhei Palmati)was prepared.The rats were treated with either CDR topically on the fracture site,or Sr R orally,or their combinations.Bone turnover biochemical markers in serum were measured.Microarchitecture of the fracture was analyzed using micro-CT after 14 and 28 d,followed by histomorphometrical analysis.RESULTS:Micro-computed tomography analysis revealed that the combined treatment of CDR with600 mg/g Sr R significantly increased the total callus density,mineralized callus volume fraction,mineralized callus mineral content and mineralized callus density of the callus after 28 d of treatment.This result was consistent with the histomorphometrical analysis on the osteoid volume.Analysis of biochemical markers showed that the combined treatments reduced the bone resorption that occurs temporarily after fracture.CONCLUSION:This study demonstrated that the combined treatment of oral Sr R and topical CDR is effective to promote fracture healing by their additive effect on promoting bone formation and retarding bone resorption.
基金This work was supported by the National Science Foundation of China(No.82002313,No.82072444,31900963)Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2020kqhm008)+2 种基金the Health Commission of Hubei Province(No.WJ2019Z009)the Wuhan Union Hospital"Pharmaceutical Technology nursing"special fund(No.2019xhyn021)the China Postdoctoral Science Foundation(No.2021TQ0118).
文摘A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.
文摘Objective: To explore the effect of fluvastatin on vascular endothelial growth factor (VEGF) in rats with osteoporosis in the process of fracture healing.Methods: Fractures at the intermediate piece of the femur were made on 72 Sprague Dawley (SD) rats (weighing initially 290-340 g and aged 6 months ) with osteoporosis after ovariectomy for three months, then these rats were divided randomly into the medication administration group (the experimental group ) and the control group, 36 rats each. In the experimental group, the rats received fluvastatin lavage (10 mg/kg per day) since the next day of operation lasting for 6 weeks, and the rats in the control group received placebo. Then the expression of VEGF and VEGF mRNA in bony callus of the two groups was measured respectively with immunohistochemistry and in situ hybridization on days of 3rd, 7th, 14th, 21st, 28th, and 42nd, and image analysis was made with real-color image analysis machine.Results: No difference was found in the cellular localization of VEGF and VEGF mRNA gene expression between the experimental group and the control group in process of fracture healing and their expression modes were almost similar. On the 14th day postoperatively, the positive extent of positive cells in the experimental group was higher than that of the control group (P < 0.05).Conclusion: Fluvastatin can promote the VEGF level in rats with osteoporosis in process of fracture healing.
基金the National Natural Science Foundation of China(Nos.61803017 and 61827802)in part funded by the Beihang University(Nos.KG12090401 and ZG216S19C8)。
文摘Fracture healing progress monitoring techniques attract global research attention due to the importance of selecting the timing of removing the fixation device.To this end,in this research,we present a piezoelectric-based smart internal fixation device,in which a piezoelectric sandwich structure is laminated to the surface of a bone plate.In the content,we explain the reasons for utilizing piezoelectric films,elaborate the mechanism of fracture monitoring,and introduce the mechanical parameters of the sensor.The simulation and experimental results show that the electrical output of the device is associated with the elastic modulus of the filler between the tested broken bones when the working load is maintained,indicating that the bone recovery progress could be successfully detected by the developed technique.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)(R01AR052674-01 and R01AR063661)and funds from the University of Connecticut Health Center.
文摘The multifaceted sequence of events that follow fracture repair can be further complicated when considering risk factors for impaired union,present in a large and growing percentage of the population.Risk factors such as diabetes,substance abuse,and poor nutrition affect both the young and old,and have been shown to dramatically impair the body’s natural healing processes.To this end,biotherapeutic interventions such as ultrasound,electrical simulation,growth factor treatment(BMP-2,BMP-7,PDGF-BB,FGF-2)have been evaluated in preclinical models and in some cases are used widely for patients with established non-union or risk/indication or impaired healing(i.e.ultrasound,BMP-2,etc.).Despite the promise of these interventions,they have been shown to be reliant on patient compliance and can produce adverse side effects such as heterotopic ossification.Gene and cell therapy approaches have attempted to apply controlled regimens of these factors and have produced promising results.However,there are safety and efficacy concerns that may limit the translation of these approaches.In addition,none of the above mentioned approaches consider genetic variation between individual patients.Several clinical and preclinical studies have demonstrated a genetic component to fracture repair and that SNPs and genetic background variation play major roles in the determination of healing outcomes.Despite this,there is a need for preclinical data to dissect the mechanism underlying the influence of specific gene loci on the processes of fracture healing,which will be paramount in the future of patient-centered interventions for fracture repair.
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.