bone diseases

骨疾病
  • 文章类型: Journal Article
    骨质疏松症(OP)是一种与低骨量和骨折风险增加有关的骨骼疾病。根尖周炎(AP)是根尖牙周炎,在射线照片上可见,常伴有根管系统感染或坏死。这两个条件,AP和OP,炎症和衰老是共同的因素,保证探索它们潜在的相互作用。这项研究检查了下奥地利州OP患者AP与牙髓治疗/未治疗牙齿之间的关系。
    作者包括425名年龄超过60岁(平均年龄68±10岁)的患者(7924颗检查过的牙齿),其中208名患者(3537颗检查过的牙齿)[女性(3027颗牙齿)和29名男性(510颗牙齿)]最初诊断并接受OP治疗,对照组为217名患者(4387颗检查过的牙齿)[187名女性(3781颗牙齿)对于AP的诊断,对初次就诊时拍摄的全景X光片和病史进行了分析.
    在接受OP治疗的患者中,AP的诊断如下:女性中有134颗(26%)接受治疗的牙齿和234颗(9%)未治疗的牙齿(511颗治疗/2516颗未治疗的牙齿),男性中有23颗(27%)接受治疗的牙齿和50颗(11%)未治疗的牙齿(83颗治疗/427颗未治疗的牙齿)。无OP的对照组包括:147颗(25%)治疗和403颗(12%)未治疗的牙齿中的女性(569颗治疗/3212颗未治疗的牙齿);男性(77颗治疗/529颗未治疗的牙齿)17颗(22%)治疗和29颗(6%)未治疗的牙齿。当根据性别比较牙髓治疗牙齿的AP时,有无OP的患者间差异无统计学意义(P>0.05)。在牙髓未治疗的牙齿中观察到相同的结果(P>0.05)。
    作者的结果表明,在接受OP治疗的女性和男性患者中,AP的发生与牙髓或非牙髓治疗的牙齿之间没有关联。
    UNASSIGNED: Osteoporosis (OP) is a bone disease linked to low bone mass and heightened fracture risk. Apical periodontitis (AP) is an inflammation of the apical periodontium, visible on radiographs, often associated with infection or necrosis of the root canal system. Both conditions, AP and OP, share inflammation and ageing as common factors, warranting exploration of their potential interactions. This study examined the association between AP and endodontically treated/non-treated teeth in patients with OP in Lower Austria.
    UNASSIGNED: The authors included 425 patients (7924 examined teeth) aged over 60 years (average age 68±10 years) with 208 patients (3537 examined teeth) [179 women (3027 teeth) and 29 men (510 teeth)] initially diagnosed and treated for OP and a corresponding control group with 217 patients (4387 examined teeth) [187 women (3781 teeth) and 30 men (606 teeth)] without an OP diagnosis. For the diagnosis of AP, the panoramic radiographs and medical history taken at the initial presentation were analysed.
    UNASSIGNED: In patients treated for OP, AP was diagnosed as follows: in 134 (26%) treated and 234 (9%) non-treated teeth among women (511 treated/2516 non-treated teeth) and in 23 (27%) treated and 50 (11%) non-treated teeth among men (83 treated/427 non-treated teeth). The control group without OP consisted of: women (569 treated/ 3212 non-treated teeth) in 147 (25%) treated and 403 (12%) non-treated teeth; men (77 treated/ 529 non-treated teeth) 17 (22%) treated and 29 (6%) non-treated teeth.When comparing AP in endodontically treated teeth according to sex, no statistically significant differences were observed between patients with and without OP (P>0.05). The same result was observed in endodontically non-treated teeth (P>0.05).
    UNASSIGNED: The authors\' results indicate that there is no association between the occurrence of AP and endodontically or non-endodontically treated teeth in female and male patients treated for OP.
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  • 文章类型: Journal Article
    背景:对于骨骼健康的人和骨质疏松症患者,建议采用富含钙和蛋白质的均衡饮食,但它也可能是重要的罕见骨病(RBD)。关于RBD和饮食的数据很少。因此,这项研究的目的是评估RBD患者的营养行为。
    方法:这种单中心,横截面,基于问卷调查的研究评估了RBD患者的营养行为(X连锁低磷酸盐血症(XLH),成骨不全症(OI),低磷酸盐血症(HPP)),骨质疏松症(OPO)患者和健康对照(CTRL)。营养问卷包括来自七个营养领域的25个问题。通过年龄调整单变量协方差分析(ANCOVA)评估社会经济因素与BMI之间的关联。
    结果:50例RBD患者(17OI,17HPP,16XLH;平均年龄48.8±15.9,26.0%男性,平均BMI26.2±5.6),51岁,OPO(平均年龄66.6±10.0,男性9.8%,平均BMI24.2±3.9)和52CTRL(平均年龄50.8±16.3,26.9%男性,平均BMI26.4±4.7)参加。二十六(52.0%)RBD,17(33.4%)OPO和24(46.1%)CTRL根据BMI超重或肥胖。只有少数RBD,OPO和CTRL每天至少摄入三份牛奶或奶制品(17.3%RBD,15.6%OPO,11.6%CTRL,p=0.453)。总的来说,在三个亚组之间观察到相似的营养行为.然而,咖啡因摄入量存在显著差异(p=0.016),水果/蔬菜汁消费量(p=0.034),每周鱼的份量(p=0.044),每周的高脂肪膳食(p=0.015)和咸味零食的消费(p=0.001)。
    结论:营养咨询,控制BMI并确保足够的钙和蛋白质摄入对于骨质疏松症患者以及罕见的骨骼疾病至关重要。维生素D似乎没有足够的饮食供应,因此,骨骼疾病患者应考虑补充。
    BACKGROUND: A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD.
    METHODS: This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA).
    RESULTS: Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, p = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption (p = 0.016), fruit/vegetable juice consumption (p = 0.034), portions of fish per week (p = 0.044), high-fat meals per week (p = 0.015) and consumption of salty snacks (p = 0.001).
    CONCLUSIONS: Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases.
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  • 文章类型: Journal Article
    背景:罕见骨病(RBD)会导致身体和感觉障碍,从而影响生活质量。流动性挑战对于有RBD的人来说很常见,前往步态分析实验室可能非常复杂。智能手机传感器可以提供远程监控。
    目的:本研究旨在通过在现实环境中使用内置的智能手机传感器来搜索和识别可用于区分RBD患者和健康人的变量。
    方法:总共,18名参与者(健康:n=9;RBD:n=9),受年龄和性别的控制,纳入本横断面研究。免费提供的应用程序(Phyphox)用于在60Hz的水平表面上行走15分钟,从内置的智能手机传感器(加速度计和陀螺仪)收集数据,而无需转弯或停止。时间步态参数,如节奏,意味着跨步时间,系数方差(CoVSt)和非线性分析,作为最大的Lyapunov指数(LLE)和样本熵(SE)在三个加速度计轴被用来区分群体和描述步态模式。
    结果:LLE(p=0.04)和z轴的SE(p=0.01),与行走过程中的平衡控制和步态规律性相关,足够敏感以区分RBD和对照。
    结论:使用智能手机传感器监测RBD患者的步态可以识别步态模式的细微变化,可用于为更大队列的评估和管理策略提供信息。
    BACKGROUND: Rare bone diseases (RBD) cause physical and sensory disability that affects quality of life. Mobility challenges are common for people with RBDs, and travelling to gait analysis labs can be very complex. Smartphone sensors could provide remote monitoring.
    OBJECTIVE: This study aimed to search for and identify variables that can be used to discriminate between people with RBD and healthy people by using built-in smartphone sensors in a real-world setting.
    METHODS: In total, 18 participants (healthy: n=9; RBD: n=9), controlled by age and sex, were included in this cross-sectional study. A freely available App (Phyphox) was used to gather data from built-in smartphone sensors (accelerometer & gyroscope) at 60 Hz during a 15-min walk on a level surface without turns or stops. Temporal gait parameters like cadence, mean stride time and, coefficient variance (CoVSt) and nonlinear analyses, as the largest Lyapunov exponent (LLE) & sample entropy (SE) in the three accelerometer axes were used to distinguish between the groups and describe gait patterns.
    RESULTS: The LLE (p=0.04) and the SE of the z-axis (p=0.01), which are correlated with balance control during walking and regularity of the gait, are sufficiently sensitive to distinguish between RBD and controls.
    CONCLUSIONS: The use of smartphone sensors to monitor gait in people with RBD allows for the identification of subtle changes in gait patterns, which can be used to inform assessment and management strategies in larger cohorts.
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  • 文章类型: Journal Article
    目的:评估在2000年1月至2010年12月期间,肾病综合征(NS)和进一步使用皮质类固醇(CS)是否会增加亚洲人群骨质疏松症的风险。
    方法:全国人群回顾性队列研究。
    方法:台湾的所有医疗机构。
    方法:共纳入28772人。
    方法:确定了2000年至2010年间新诊断为NS的26614例个体,并将其纳入研究。在索引日期之前没有NS诊断的26614名个体作为对照进行年龄匹配。在诊断NS或确定相同的指数日期之前诊断出骨质疏松症,年龄,性别和NS相关的合并症被调整。
    方法:确定有NS病史的患者发生骨质疏松症的风险差异。
    结果:调整协变量后,在NS队列中,骨质疏松症的风险是非NS队列中的3.279倍,当测量超过11年后NS诊断。分层显示年龄超过18岁,充血性心力衰竭,高脂血症,慢性肾病,肝硬化和NS相关疾病,包括糖尿病,乙型肝炎感染,丙型肝炎感染,淋巴瘤和甲状腺功能减退症,NS队列中骨质疏松症的风险增加,与非NS队列相比。此外,使用CS的NS患者的骨质疏松风险显著较高(校正HR(aHR)=3.397).NS患者骨质疏松的风险与髋部和椎体骨折的风险呈正相关(aHR分别为2.130和2.268)。NS与随后的骨质疏松症风险之间存在显着关联。
    结论:NS患者,特别是那些用CS治疗的,应评估随后的骨质疏松症风险。
    OBJECTIVE: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010.
    METHODS: Nationwide population-based retrospective cohort study.
    METHODS: All healthcare facilities in Taiwan.
    METHODS: A total of 28 772 individuals were enrolled.
    METHODS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted.
    METHODS: To identify risk differences in developing osteoporosis among patients with a medical history of NS.
    RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis.
    CONCLUSIONS: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.
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  • 文章类型: Journal Article
    骨骼破坏导致的身体功能下降,疼痛,贫血,感染,体重减轻在多发性骨髓瘤(MM)中很常见。骨髓瘤骨病挑战体育锻炼。对新诊断的MM患者体育锻炼的效果和安全性的了解有限。在一个随机的,对照试验,我们研究了为期10周的个性化体育锻炼计划对身体功能的影响,身体活动,瘦体重(LBM),骨矿物质密度(BMD),生活质量(QoL),以及新诊断为MM的患者的疼痛。评估了溶骨病,运动也相应调整。主要结果:膝关节伸展强度。次要结果:六分钟步行测试,30-s坐立测试(SST),握力,体力活动水平,LBM,BMD,QoL,和痛苦。在干预前后进行测量,6个月和12个月后。我们纳入了100名患者,86人可评价;干预组(IG)44人,对照组(CG)42人。组间没有观察到统计学上的显著差异。膝关节伸展强度在IG中下降(p=.02)。SST,有氧能力,两组的全球QoL均有所改善。无论疼痛结果如何,IG中的疼痛均持续下降。在新诊断的MM患者中,未观察到体育锻炼的重大安全性问题。
    Reduced physical function caused by bone destruction, pain, anemia, infections, and weight loss is common in multiple myeloma (MM). Myeloma bone disease challenges physical exercise. Knowledge on the effects and safety of physical exercise in newly diagnosed patients with MM is limited. In a randomized, controlled trial, we studied the effect of a 10-week individualized physical exercise program on physical function, physical activity, lean body mass (LBM), bone mineral density (BMD), quality of life (QoL), and pain in patients newly diagnosed with MM. Lytic bone disease was assessed, and exercise was adjusted accordingly. Primary outcome: knee extension strength. Secondary outcomes: Six-Minute-Walk-Test, 30-s Sit-to-Stand-Test (SST), grip strength, level of physical activity, LBM, BMD, QoL, and pain. Measurements were conducted pre- and post-intervention, and after 6 and 12 months. We included 100 patients, 86 were evaluable; 44 in the intervention group (IG) and 42 in the control group (CG). No statistically significant differences between groups were observed. Knee extension strength declined in the IG (p = .02). SST, aerobic capacity, and global QoL improved in both groups. Pain decreased consistently in the IG regardless of pain outcome. No significant safety concerns of physical exercise in newly diagnosed patients with MM were observed.
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  • 文章类型: Journal Article
    背景:肝性骨营养不良是指与慢性肝病相关的骨骼疾病,包括接受肝移植(LT)的儿童。这项研究的目的是量化LT前后儿童病理性骨折(PF)的患病率,并确定其发生的相关因素。
    方法:这项回顾性研究包括2005年1月至2020年12月接受LT的0-18岁儿童。患者人口统计数据,提取骨折的类型和解剖位置以及生物检查。在3个时间点评估变量:LT上市时的T-1;LT时的T0和LT后1年的T+1。
    结果:共有105名儿童(49[47%]名女性)被纳入本研究。LT时的中位年龄为19个月(范围0-203)。22例患者(21%)经历了65PF,LT之前有11个孩子,LT后10,1在LT之前和之后。观察到以下变量与PF相关:在T-1时,低体重和身高z分数,和延迟的骨龄;在T0,低体重和身高z评分,高总胆红素和结合胆红素;在T+1时,持续的低身高z评分。在T-1、T0和T+1时,PF组患者在补钙和/或营养支持下明显更多。
    结论:需要LT的儿童中有五分之一以上在LT之前或之后维持PF。体重和身高z评分低以及骨龄延迟的患者发生PF的风险增加。营养支持仍然很重要,即使到目前为止,它还不能完全抵消PF的风险。
    BACKGROUND: Hepatic osteodystrophy refers to bone disorders associated with chronic liver disease, including children undergoing liver transplantation (LT). The aim of this study was to quantify the prevalence of pathological fractures (PF) in children before and after LT and to identify associated factors for their occurrence.
    METHODS: Children aged 0-18 years who underwent LT from 1/2005 to 12/2020 were included in this retrospective study. Data on patient demographics, types and anatomical locations of fracture and biological workups were extracted. Variables were assessed at 3 time points: T - 1 at the moment of listing for LT; T0 at the moment of LT and T + 1 at 1-year post-LT.
    RESULTS: A total of 105 children (49 [47%] females) were included in this study. Median age at LT was 19 months (range 0-203). Twenty-two patients (21%) experienced 65 PF, 11 children before LT, 10 after LT, and 1 before and after LT. The following variables were observed as associated with PF: At T - 1, low weight and height z-scores, and delayed bone age; at T0, low weight and height z-scores, high total and conjugated bilirubin; at T + 1, persistent low height z-score. Patients in the PF-group were significantly more under calcium supplementation and/or nutritional support at T - 1, T0 and T + 1.
    CONCLUSIONS: More than one in five children needing LT sustain a PF before or after LT. Patients with low weight and height z-scores and delayed bone age are at increased risk for PF. Nutritional support remains important, even if to date it cannot fully counteract the risks of PF.
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  • 文章类型: Journal Article
    背景:锁定钢板通常用于粉碎的固定,假体周围和骨质疏松性骨折。这些钢板用螺钉固定在骨头上,在板和螺钉之间形成固定角度的稳定连接。在这项体外生物力学研究中,我们的目的是评估和比较新型锁定板-锁定自重螺钉模型与FDA批准的经典锁定板。
    方法:利用SawbonePCF-15骨质疏松骨模型来模拟骨质疏松骨条件。使用两个螺钉将经典的锁定板和新颖的锁定板-锁定自发螺钉模型连接到这些骨模型。通过拉出测试测量螺钉与骨块的连接强度。
    结果:与目前的锁定钢板模型相比,新型锁定钢板-锁定螺钉模型对骨质疏松性骨模型的附着强度为84.38%。
    结论:结论:锁定钢板中的一个重要问题是锁定自锁螺钉的高拔出风险可以通过我们提出的新模型得到解决,并且有机会获得更好的购买,尤其是在骨质疏松的骨骼中。
    BACKGROUND: Locking plates are commonly used for the fixation of comminuted, periprosthetic and osteoporotic bone fractures. These plates are secured to the bone with screws, creating a stable connection with fixed angle between the plate and the screws. In this biomechanical in vitro study, our aim is to evaluate and compare the novel locking plate-locking spongious screw model with FDA approved classical locking plate.
    METHODS: Sawbone PCF-15 osteoporotic bone model was utilized to simulate osteoporotic bone conditions. Two screws were used to attach both the classical locking plate and the novel locking plate-locking spongious screw model to these bone models. The attachment strength of the screws to the bone blocks was measured by pull-out tests.
    RESULTS: Novel locking plate-locking spongious screw model exhibited an 84.38% stronger attachment to the osteoporotic bone model compared to the current locking plate model.
    CONCLUSIONS: In conclusion, one of the important problems in the locking plates which is the high Pull-out risk of the locking spongious screws can been resolved with our proposed new model and has a chance of having a better purchase especially in osteoporotic bones.
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  • 文章类型: Journal Article
    骨质疏松症是最常见的骨骼疾病。我们的数据估计,2018年德国普通人群中约有587万例骨质疏松症。只有30%的被保险人患有骨质疏松性骨折和/或确诊为骨质疏松症,收到了合适的处方。
    目的:骨质疏松是最常见的骨病。它特别影响老年人,并增加无创伤骨折的风险。这项研究的目的是估计50岁以上的德国普通人群中骨质疏松症的患病率,并收集有关骨质疏松症特异性药物处方频率的数据,以评估治疗差距。
    方法:回顾性分析来自柏林应用健康研究所(InGef)2018年数据库的50岁以上根据法定医疗保健计划投保的个人的匿名数据(研究人群)。根据骨质疏松症的诊断确定患有骨质疏松症的被保险人,骨质疏松症特有的处方,或者骨质疏松性骨折.因此,我们估计了年龄≥50岁的德国普通人群中骨质疏松症的患病率.诊断的普遍性,骨折,并为研究人群确定处方,并按年龄和性别分层.
    结果:在1,599,299名被保险人的研究人群中,骨质疏松的患病率为15.9%.据估计,德国总人口约有587万例骨质疏松症。81.6%的病例为女性。在研究人群中,有30.0%的被保险人被诊断出患有骨质疏松症和/或患有骨质疏松性骨折。
    结论:德国的骨质疏松症患病率很高。只有一小部分可能需要骨质疏松症特异性治疗的人实际接受了它。
    Osteoporosis is the most common bone disorder. Our data gives an estimate of around 5.87 million cases of osteoporosis in the general German population in 2018. Only 30% of insured individuals who suffered an osteoporotic fracture and/or had a confirmed diagnosis of osteoporosis, received an appropriate prescription.
    OBJECTIVE: Osteoporosis is the most common bone disorder. It particularly affects elderly people and increases the risk of atraumatic fractures. The aim of this study was to estimate the prevalence of osteoporosis in the general German population aged ≥ 50 years and to collect data on the frequency of prescription of osteoporosis-specific medication in order to assess the treatment gap.
    METHODS: Retrospective analysis of anonymized data of individuals aged ≥ 50 years insured under statutory healthcare schemes from the database of the Institute for Applied Health Research Berlin (InGef) for 2018 (study population). Insured individuals with osteoporosis were identified based on osteoporosis diagnoses, osteoporosis-specific prescriptions, or osteoporotic fractures. Thus, we estimated the prevalence of osteoporosis in the general German population aged ≥ 50 years. The prevalence of diagnoses, fractures, and prescriptions was determined for the study population and stratified by age and gender.
    RESULTS: Within the study population of 1,599,299 insured individuals, a prevalence of osteoporosis of 15.9% was determined. This estimated approximately 5.87 million cases of osteoporosis for the general German population. 81.6% of the cases were women. Osteoporosis-specific prescriptions were received by 30.0% of the insured individuals in the study population who had been diagnosed with osteoporosis and/or suffered an osteoporotic fracture.
    CONCLUSIONS: Germany has a high prevalence of osteoporosis. Only a small portion of individuals who may require osteoporosis-specific treatment actually receive it.
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    在骨丢失疾病中促进骨再生的效率是重要的临床挑战。传统疗法通常无法实现更好的治疗结果和更短的治疗时间。然而,近年来,与传统细胞疗法相比,细胞外囊泡(EV)由于其在骨再生中具有特殊的成骨功能和出色的治疗效果而受到广泛关注。由于其各种生理功能,电动汽车已成为组织缺损再生的有希望的疗法,如调节免疫反应,促进组织修复和再生。此外,电动汽车具有良好的生物相容性,低免疫原性,和长期稳定,并可以通过预处理和其他方法进行改进。研究细胞外囊泡促进骨再生的机制以及使用各种方法将来自不同来源的EV应用于骨缺损的动物模型的研究已经增加。因此,本文综述了用于骨再生的电动汽车的类型,他们的来源,角色,输送途径,支架生物材料,和应用。
    Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications.
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