Pulp health and calcific healing of a complicated crown–root fracture with additional root fracture in a maxillary incisor: A case report

BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in theliterature.CASE SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical level.After the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival overgrowth.Cone-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival overgrowth.CONCLUSION This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.

Value of negative pressure sealing drainage on wound healing of Gustilo IIIB and IIIC open fractures

BACKGROUND Gustilo III fractures have a high incidence and are difficult to treat.Patients often experience difficulty in wound healing.Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis.AIM To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures.METHODS Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People’s Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects.They were divided into a study group(n=40,healed with negative pressure closed drainage)and a control group(n=40,healed with conventional dressing changes)according to the variation in the healing they received.The efficacy of the clinical interventions,the variations in the regression indicators(time to wound healing,time to fracture healing,time to hospitalization),and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention.RESULTS The total effective rate of patients among the study group was 95.00%(38/40),which was notably higher than 75.00%(30/40)among the control group(P<0.05).The wound healing time,fracture healing time,and hospital stay of the patients in the study group was shorter than the control group(P<0.05).After the intervention,the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group(P<0.05).CONCLUSION Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury.It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.

Axial load-share ratio testing to assess the healing of open tibial fractures treated with the Taylor Spatial Frame

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.

Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression

Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

Accelerated fracture healing by osteogenic Ti45Nb implants through the PI3K–Akt signaling pathway

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.

EXPERIMENTAL STUDY ON THE BLOOD BIOCHEMICAL PARAMETERS FOR THE PROMOTION OF FRACTURE HEALING BY MS

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.

β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model

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.

Non-steroidal anti-inflammatory drugs in postoperative hand fracture management:Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs(NSAIDs)on postoperative recovery in hand fracture patients,amidst shifting pain management strategies away from opioids due to their adverse effects.With hand fractures being significantly common and postoperative pain management crucial for recovery,the potential of NSAIDs offers a non-addictive pain control alternative.However,the controversy over NSAIDs'effects on bone healing—stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union—necessitates further investigation.Despite a comprehensive literature search,the study finds a lack of specific research on NSAIDs in postoperative hand fracture management,highlighting an urgent need for future studies to balance their benefits against possible risks.

Application of ultrasonic inspection in monitoring dynamic healing of mandibular fracture in rabbit model

Objective:To investigate the feasibility of ultrasonic diagnosis for monitoring fracture healing. Methods:Thirty rabbit models with fraction of mandible body were established by surgically removing partial lower jawbone.At the 1st,2nd,4th,6th,8th and 12th week after the operation, they were examined by X-ray and ultrasound,respectively.All detection results were scored according to a generally accepted standard.Spearman rank correlation analysis was conducted to explore the relationship between the results of the two inspection methods.Results:In each healing stage,the results of the ultrasonic inspection were basically consistent with those of the X-ray examination,as supported by a Spearman rank correlation coefficient of 0.892(P【0.001). Conclusions:Non-invasive ultrasonic inspection can be used instead of X-ray examination to monitor and diagnose fracture healing.

Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.

Use of Teriparatide to improve fracture healing: What is the evidence?

Teriparatide is a recombinant form of the biologicallyactive component of Parathyroid hormone. It has been shown to increase bone mass and prevent fractures in osteoporotic bone. It is licensed by the Food and Drug Administration for the treatment of Osteoporosis. Over the last decade, a growing body of evidence has accumulated suggesting a role for Teriparatide in the management of fractures. Studies in both normal and delayed healing models have shown improvement in callus volume and mineralisation, bone mineral content, rate of successful union and strength at fracture sites. However most of these results have been derived from animal studies. The majority of this research on humans has comprised low level evidence, with few randomised controlled trials, many case reports and case series. Nevertheless, the results from these studies seem to support research from animal models. This has led to a growing number of clinicians using Teriparatide "off license" to treat fractures and non-unions in their patients. This review presents a critical appraisal of the current evidence supporting the use of Teriparatide for fracture healing, delayed unions and non unions and in the setting of osteoporotic fractures, the studies producing this evidence and their transferability to human beings.

An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP^(+)mononuclear cells and PDGF-BB secretion

Osteoporosis(OP)is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures.Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed.We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation.We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment.The secretion of platelet-derived growth factor-BB(PDGF-BB),the number of tartrate-resistant acid phosphatase-positive(TRAP+)mononuclear cells,and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice.The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP-1"cells.These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP4 mononuclear cells.To test the therapeutic potential of the Siglec-15 neutralizing antibody,we injected the antibody in an ovariectomy-induced osteoporotic mouse model,which mimics postmenopausal osteoporosis in women,and in two fracture healing models because fracture is the most serious health consequence of osteoporosis.The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis.Of note,the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models.Thus,the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture.

Bone Injury and Fracture Healing Biology

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

Inducible expression of Wnt7b promotes bone formation in aged mice and enhances fracture healing

There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested,Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.

Effects of aspirin on fracture healing in OPF rats

Objective:To study the effect of aspirin on healing process of osteoporotic fracture(OPF)in rats.Methods:A total of 50 female Wistar rata aged 3 months were randomly divided into observation group and control group,castration method was adopted to establish the osteoporosis(OP)model.After artificial preparing fractures on the midpoint of left femur,fixing gram needle intramedullary.OPF modeling was complete.Aspirin lavage of 33 mg once a day was adoptde in observation group after modeling,same amount of normal saline was used in the control as placebo.From eash group,selected 5 rats at the 2nd.4th,8th and 12th week after modeling to measure the bone mineral density(BMD)and histogical examination of the fracture callus,radiology observation was conducted at the 8th and 12th week.Left femur biomechanical measurement was taken at the 12th week.Results:BMD values of observation group at each time point were significantly higher than that of the control group after modeling(P<0.05);Histological observation showed that at the 8th week,the endochondral ossification process of observation group was faster than that of observation group,with fuzzy fracture line in observation group and clear fracture line in observtion group;at the 12th week,fracture line disappeared in observation group,fracture line of the control group was fuzzy at the same time;three-point bending load of the left femur in observation group rats was significantly higher than that of control group after12 weeka(P<0.05).Conclusions:Asporin can accelerate the healing of new callus in OPF rats,increase bone density and biomechanics strength,and promote fracture of osteporotic rats.

AN IMMUNOCYTOCHEMICAL STUDY OF BONE MORPHOGENETIC PROTEIN IN EXPERIMENTAL FRACTURE HEALING OF THE RABBIT MANDIBLE

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.

Efficacy of high resolution computed tomography for detection of early healing in scaphoid fractures

Background: While plain radiography is commonly used to assess scaphoid fracture, this imaging modality may not accurately demonstrate early bone healing. This investigation evaluates the utility of 64-slice CT in the detection of early fracture healing compared to plain radiographs and magnetic resonance imaging (MRI). Methods: Outpatients attending follow-up visits for scaphoid fractures at Hamilton General Hospital were included in this investigation. Inclusion criteria included outpatients over age of 18 who consented to attend a follow-up visit for the scaphoid fracture at 6 weeks for X-Ray, 64-slice CT and MRI scan to monitor fracture healing. Assessment of healing was independently interpreted by two radiologists specialized in musculoskeletal imaging. A total of 7 adult outpatients were accrued, with each case classified as healing, not healing, or equivocal for plain radiography and 64-slice CT scan. Results: For plain radiographs, the level of interrater agreement for evidence of healing was 57% (4/7) cases. When comparing this to CT scans, there was no discrepancy between radiologists as 100% (7/7) were found to have evidence of healing. The 64-slice CT scan demonstrated evidence of early trabecular continuity in all cases, including radiographs that were interpreted as equivocal. Conclusion: This study can be considered a pilot project for the efficacy of 64-slice CT in the assessment of early healing of scaphoid fractures. For clinicians, the multiplanar reconstruction images allows for more accurate assessment of fractures than plain radiography. CT scans are able to penetrate through bony callus that may obscure visualization of healing in plain radiography, demonstrate trabecular continuity better than plain radiographs, are readily accessible and provide faster imaging acquisition. The observations from this study may have implications in terms of duration and type of casting applied, timing of strengthening exercises, and avoiding unnecessary surgery which affect patient morbidity and cost of care.

Mice with a heterozygous Lrp6 deletion have impaired fracture healing

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.

Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture

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.

Effects of immune cells on mesenchymal stem cells during fracture healing

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.