Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

Understanding wound healing in obesity

Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.

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.

Enhancement of Periodontal Healing by Application of a Novel Ointment Compared with Hyaluronic Acid, Histological Observation in Animal Model

Objectives:?The early healing of the periodontal wound in oral cavity may be critical to the treatment outcome. Thus, we made a novel ointment based on natural constituents that our recent investigation suggested a positive therapeutic effects on gingival wounds. The present study was conducted to evaluate the role of this novel biomaterial on periodontal wound healing including soft as well as hard tissue. Materials and Methods: Experimental periodontitis was induced by wire tied around the cement-enamel junction of I2, P1, P3?and M1?in six adult, healthy beagle dogs. After 3 months, mucoperiostal flap elevated and root surfaced was thoroughly scaled and planed. Randomly, three materials including our ointment with two different ratios including materials A and B and hyluronic acid were applied topically and then the flaps were repositioned and sutured. Three dogs at day 7 and the three remaining ones two weeks post-surgery were sacrificed and histological changes were monitored. Results: The result of this study showed that the local applications of this novel ointment promoted the healing process particularly fibroblast proliferation and collagen density remarkably in comparison with hyaluronic acid and control group. Besides, histological finding of our material revealed that in general terms had all the hallmarks of complete healing two weeks post operatively. Conclusion: Our novel material appeared to have outstanding effect on periodontal wound healing which can improve the periodontal healing consequences and provide better strength of periodontal wound flap. From a clinical standpoint, it could play an important role for better repair in diabetic patients who frequently present difficulties in mucosal and cutanous wound healing.

Evaluation on Self-healing Mechanism and Hydrophobic Performance of Asphalt Modified by Siloxane and Polyurethane

In order to inhibit and remove the thin ice and extend the lifetime of the damaged bridge, the self-healing mechanism and hydrophobic performance of asphalt modified by siloxane and polyurethane (ASP) were studied by dynamic shear rheology (DSR), fluorescence microscope (FM), atomic force microscope (AFM), the fracture-healing-re-fracture test and molecular simulations. The experimental results indicated that the selfhealing capability of ASP increased with increasing heating time and temperature. Furthermore, the addition of siloxane could improve the reaction energy barrier and complex modulus, and it is believed that the self-healing is a viscosity driven process, consisting of two parts namely crack closure and properties recovery. Contact angle of ASP increased with the increasing siloxane content and it deduced that the siloxane could improve the hydrophobic performance of ASP and the ASP molecule model could simulate well the self-healing mechanism and hydrophobic performance of ASP.

Healing Temperature of Hybrid Structures Based on Genetic Algorithm

The healing temperature of suspen-dome with stacked arches(SDSA)and arch-supported single-layer lattice shell structures was investigated based on the genetic algorithm. The temperature field of arch under solar radiation was derived by FLUENT to investigate the influence of solar radiation on the determination of the healing temperature. Moreover, a multi-scale model was established to apply the complex temperature field under solar radiation. The change in the mechanical response of these two kinds of structures with the healing temperature was discussed. It can be concluded that solar radiation has great influence on the healing temperature, and the genetic algorithm can be effectively used in the optimization of the healing temperature for hybrid structures.

In-depth examination of hyperproliferative healing in two breeds of Sus scrofa domesticus commonly used for research

Background:Wound healing can result in various outcomes,including hypertrophic scar(HTS).Pigs serve as models to study wound healing as their skin shares physi-ologic similarity with humans.Yorkshire(Yk)and Duroc(Dc)pigs have been used to mimic normal and abnormal wound healing,respectively.The reason behind this differential healing phenotype was explored here.Methods:Excisional wounds were made on Dc and Yk pigs and were sampled and imaged for 98 days.PCR arrays were used to determine differential gene expression.Vancouver Scar Scale(VSS)scores were given.Re-epithelialization was analyzed.H&E,Mason's trichrome,and immunostains were used to determine cellularity,col-lagen content,and blood vessel density,respectively.Results:Yk wounds heal to a“port wine”HTS,resembling scarring in Fitzpatrick skin types(FST)I-III.Dc wounds heal to a dyspigmented,non-pliable HTS,resembling scarring in FST IV-VI.Gene expression during wound healing was differentially regulated versus uninjured skin in 40/80 genes,15 of which differed between breeds.Yk scars had a higher VSS score at all time points.Yk and Dc wounds had equivalent re-epithelialization,collagen disorganization,and blood vessel density.Conclusions:Our findings demonstrate that Dc and Yk pigs can produce HTS.Wound creation and healing were consistent among breeds,and differences in gene expression were not sufficient to explain differences in resulting scar phenotype.Both pig breeds should be used in animal models to investigate novel therapeutics to provide insight into a treatment's effectiveness on various skin types.

A Control System Design to Establish Dose-Response Relationships in Wound Healing Therapy

Advanced biophysical wound healing therapies can apply mechanical, electrical, or light energy to re-stimulate healing processes in chronic wounds. Despite the growing evidence of the clinical efficacy of these therapies, the optimal treatment stimulation parameters remain unknown and there are no standard treatment protocols. We introduce a closed-loop control design as an experimental system to study the dose-response of wound healing therapy treatment within a prescribed multidimensional and multimodal stimulation parameter space. Systems engineering approaches are applied to the control problem for estimation of a transfer function and model equations derived for use in optimal model-based control. The experimental control system design consisted of simultaneous application of biophysical energies inputted into a wound system. A study design set up including the use of negative pressure wound therapy, electrical stimulation therapy, and photobiomodulation device systems was described. Treatment stimulation parameters were selected from experimental ranges used in the scientific literature. Classical control methods and model-based control were suggested for model selection and evaluation and design of the overall control system. An experimental design for multimodal biophysical wound healing therapy control system is introduced to establish the dose-response interactions for development of therapeutic applications and device design.

Vaccination effect on a stochastic epidemic model with healing and relapse

In this work,we consider a stochastic epidemic model with vaccination,healing and relapse.We prove the existence and the uniqueness of the positive solution.We establish sufficient conditions for the extinction and the persistence in mean of the stochastic system.Moreover,we also establish sufficient conditions for the existence of ergodic stationary distribution to the model,which reveals that the infectious disease will persist.The graphical illustrations of the approximate solutions of the stochastic epidemic model have been performed.

The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

This study developed an animal model of surgically wounded submandibular glands （SMGs） and investigated the effects of collagen gel with basic fibroblast growth factor （bFGF） on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF （bFGF group） or without bFGF （control group）. In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day （AOD） 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, g-smooth muscle actin （αSMA）, CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin 19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration.

DAMAGE AND CREEP MODEL FOR ROCK SALT AS WELL AS ITS VALIDATION

The constitutive model Hou/Lux,based on continuum damage mechanics and on the material model Lubby2 is presented and the damage,the healing of damage,the tertiary creep and the creep rupture of rock salt described. An application shows how phenomena observed in laboratory tests on axially perforated cylinder sample, such as softening, dilatancy, spalling and radial deformation into the axial bore as well as spalling can be numerically simulated with the model Hou/Lux. Furthermore,it is then evaluated against the measured permeability and stress profiles of a 37-year-old drift at the Sondershausen minein,Germany. Satisfactory agreement is obtained between the calculated and measured data.

An end-to-end anastomosis model of guinea pig bile duct:A 6-mo observation

AIM:To establish the end-to-end anastomosis (EEA) model of guinea pig bile duct and evaluate the healing process of bile duct.METHODS:Thirty-two male guinea pigs were randomly divided into control group,2-,3-,and 6-mo groups after establishment of EEA model.Histological,immunohistochemical and serologic tests as well as measurement of bile contents were performed.The bile duct diameter and the diameter ratio (DR) were measured to assess the formation of relative stricture.RESULTS:Acute and chronic inflammatory reactions occurred throughout the healing process of bile duct.Serology test and bile content measurement showed no formation of persistent stricture in 6-mo group.The DR revealed a transient formation of relative stricture in 2-mo group in comparation to control group (2.94 ± 0.17 vs 1.89 ± 0.27,P=0.004).However,this relative stricture was released in 6-mo group (2.14 ± 0.18,P=0.440).CONCLUSION:A simple and reliable EEA model of guinea pig bile duct can be established with a good reproducibility and a satisfactory survival rate.

Preliminary Investigation of Formulated Herbal Ointment Demonstrates Amelioration of Excision Wound in Experimental Rabbit Model Compared with Silver Sulfadiazine

In light of the use of Lannea barteri in the management of diverse illnesses and treatment of wounds in traditional medicine, the current study was conducted to assess the wound-healing efficacy of crude aqueous extract of the stem bark of Lannea barteri and its shea butter formulated ointment using an excision wound model in the rabbit. The herbal ointment (5%, w/w) exhibited a significant wound healing activity, showing 99.9% ± 0.3% wound contraction at the end of the experiment (24th day). There was no significant difference (p > 0.05) between the 5% (w/w) herbal ointment compared with Silver Sulphadiazine cream (positive control), which showed a 97.8% ± 1.0% rate of excision wound contraction on day 24. Compared with the negative control group (administered with only shea butter), the wound healing activity of the ointment was significant (p Lannea barteri for the treatment of wounds and demonstrates that shea butter usage as a base in formulating an herbal ointment might aid in topical application for wound repair and regeneration, as well as the potential for enhanced wound healing.

Influence of Medical Model on Therapeutic Environment

In its development history, man has always tried to be close to nature, and get physical and spiritual help from the nature. According to the development of medical model from the deity worship to modern medical science, a near-nature and ecological therapeutic and recuperative model has been more favored, thus in modern therapeutic environment, proper landscape designs can be combined with effective medical methods to achieve physical and mental immunoregulation and balance using natural and quality climatic factors. This paper introduced the development of natural science and medicinal model in different periods, and analyzed their impact on environment, concluded the benefi ts of therapeutic medicine, and demonstrated the signifi cance of therapeutic environment and landscape healing as the therapeutic factors for facilitating human rehabilitation from the perspective of therapeutic medicine. Taking "evidence-based design" as the basis of therapeutic environment design, this paper proposed landscape design methods for the therapeutic environment, in order to provide people opportunities for closing to, sharing and participating in the nature, help people to relax physically and psychologically using the positive impact of natural environment on human spirits, relieve their stress, and achieve physical and psychological peace. In addition, the development tendency of therapeutic environment in China was predicted according to the actual conditions of urban society.

踝关节骨折伴三角韧带损伤术后骨折延迟愈合的风险预测模型及护理对策

目的探讨踝关节骨折伴三角韧带损伤术后骨折延迟愈合的风险因素,进一步构建风险预测模型,为临床及时采取针对性护理对策提供依据。方法选取2020年1月至2023年6月郑州大学第一附属医院踝关节骨折伴三角韧带损伤术后骨折延迟愈合患者248例作为延迟组,同期选取术后骨折正常愈合患者265例作为未延迟组,收集两组资料,logistic回归分析踝关节骨折伴三角韧带损伤患者术后骨折延迟愈合的影响因素,进一步构建nomogram预测模型并进行验证。结果年龄、开放性骨折、内固定松动、骨质疏松、维生素缺乏、合并糖尿病、合并OSAHS、营养不良、激活素A是踝关节骨折伴三角韧带损伤患者术后骨折延迟愈合的危险因素,康复锻炼依从性、延续康复指导、术后中医药治疗、鸢尾素是其保护因素;nomogram预测模型预测术后骨折延迟愈合的曲线下面积(AUC)为0.874(95%CI:0.762~0.913),预测敏感度、特异度依次为86.75%、72.16%。结论延迟愈合是踝关节骨折伴三角韧带损伤患者术后常见问题,与多种因素有关,加强nomogram预测模型构建可及时识别高危人群,以此为依据及时采取针对性护理对策可能是促进骨折愈合、降低延迟愈合风险的新途径。

基于LASSO变量选择的结直肠癌病人术后吻合口愈合不良预测模型的构建与分析

目的 构建基于LASSO变量选择的结直肠癌病人术后吻合口愈合不良预测模型,并分析该模型对吻合口预后不良预测效能。方法 前瞻性纳入2018年3月~2023年1月期间于我院接受治疗的215例结直肠癌病人为研究对象,所有病人均接受腹腔镜结直肠癌根治术,术后对所有病人进行为期30天的随访,根据有无发生吻合口愈合不良分为两组,愈合不良组24例,预后良好组191例。收集病人的一般资料及临床资料,应用LASSO回归模型筛选具有非0系数的相征因素,构LASSO-Logistic回归模型分析导致病人发生吻合口愈合不良的相关因素,绘制受试者工作特征曲线(ROC),计算受试者工作特征曲线下面积(AUC)、敏感度及特异度;采用Bootdtrap法进行500次重复抽样进行验证。结果 愈合不良组男性比例大于愈合良好组;愈合不良组白细胞(WBC)、C反应蛋白(CRP)水平均高于愈合良好组,差异有统计学意义(P<0.05);愈合不良组手术时间长于愈合良好组,肿瘤直径>4 cm、肿瘤下缘与肛周距离≤7 cm、术前有新辅助化疗、肿瘤分期为Ⅲ~Ⅳ期例数显著多于愈合良好组,差异有统计学意义(P<0.05);Logistic回归筛显示,手术时间、术前接受新辅助化疗、肿瘤下缘与肛周距离以及圆周肿瘤生长是吻合口愈合不良的预测因素;根据Logistic回归绘制ROC曲线,得到AUC为0.892(95%CI:0.813~0.945),敏感性为75.81%,特异性为89.47%。Youden指数为0.6528;利用Bootdtrap技术绘制模型的校准曲线得知模型具有较好的预测效能。结论 手术时间长、术前接受新辅助化疗、肿瘤下缘与肛周距离<7 cm以及圆周肿瘤生长是影响结直肠癌术后病人发生吻合口愈合不良的危险因素,构建的预测模型可用于吻合口愈合不良人群的筛选且具有较好的预测效能。

使用数学模型对髁突颈骨折愈合过程中骨与软骨组织变化的研究

目的 使用数学模型模拟大鼠髁突颈骨折愈合过程中成骨与成软骨的动态变化过程,探索髁突颈骨折的愈合模式。方法 构建模拟大鼠髁突颈骨折愈合的数学模型,并统计该数学模型28 d内不同时间点生成的各参数(mb, mc, cb和cc)的数值,进而拟合骨、软骨、成骨细胞及成软骨细胞的密度云图和生长曲线并推算成骨方式。结果 数学模型模拟的骨面积比与大鼠骨折实验所测接近(P>0.05)。数学模型模拟的密度云图显示,在骨折后第3天至第7天成骨集中在骨膜周围,在第7天至第21天成骨集中在软骨所在区域并逐渐替代软骨。骨生长曲线与软骨生长曲线在骨折后第5至第8天与第21至第28天正相关,与第8至第14天呈负相关。成骨细胞生长曲线和成软骨细胞生长曲线均呈现先升后降的趋势,成软骨细胞在第6天达到最大密度,成骨细胞则在第13天达到最大密度。结论 数学模型能有效模拟大鼠髁突颈骨折愈合过程,可动态展示该过程中成骨与成软骨的动态变化,为研究髁突颈骨折的愈合方法提供了新思路。

姜黄素对糖尿病小鼠皮肤创面愈合的影响

目的研究姜黄素对糖尿病小鼠创面愈合的影响。方法采用噻唑蓝(MTT)检测姜黄素对成纤维细胞活性影响。氧自由基(ROS)检测试剂盒检测姜黄素对过氧化氢诱导的成纤维细胞中ROS的清除效果。qRT-PCR检测姜黄素对脂多糖诱导RAW 264.7巨噬细胞炎症因子(CD86、IL-6、CD206及ARG1)mRNA表达影响。腹腔注射链脲佐菌素建立糖尿病创面模型。苏木精-伊红(HE)、马松(Masson)染色评估创面愈合与组织形态学变化,免疫荧光染色法测定皮肤组织α-平滑肌肌动蛋白、CD86、CD206表达。结果姜黄素在浓度<20 mol·L^(-1)对成纤维细胞活性没有显著影响,并可清除过氧化氢诱导的成纤维细胞内的ROS;姜黄素降低脂多糖诱导的RAW 264.7巨噬细胞CD86、IL-6 mRNA表达量,同时增加CD206、ARG1 mRNA表达量。体内给药后,与对照组比较,姜黄素(15、30 mg·mL^(-1))组伤口闭合率加快(P<0.01),肉芽组织明显增加,胶原蛋白的沉积明显增多,CD206的表达明显增高(P<0.01),CD86的表达明显减少(P<0.01),且姜黄素(30 mg·mL^(-1))组伤口中平滑肌α-肌动蛋白表达量较小剂量姜黄素组明显增加(P<0.01)。结论姜黄素通过抗炎、抗氧化作用,促进糖尿病小鼠皮肤创面的肉芽组织增生和胶原沉积,进而加快糖尿病创面的愈合。

基于原位测量的交直流复合电压对金属化膜自愈特性影响的研究

干式直流金属化膜电容器由于其具有特殊的“自愈”特性,在投入使用前可通过“赋能”工艺去除电弱点,相比于箔式电容器,其工作电压更高,储能密度更大。为此,搭建了金属化膜自愈特性原位测试平台,研究了交直流叠加下金属化膜自愈特性的演变规律,分析了在温度、压强等复杂应力作用下,不同交直流复合电压对金属化膜自愈特性的作用机制。同时依据温度实验中发现的现象和得出的结论,搭建了自愈热力学模型,从热力学理论的角度上明确了焦耳热为自愈能量的主要来源,经过仿真计算后发现,热力学模型在0.1 MPa低压强下呈现很好的拟合效果,但在10 MPa高压强下误差较大。

三七总皂苷上调浓缩生长因子释放促进大鼠骨折愈合

背景:研究表明,三七总皂苷和浓缩生长因子均能促进骨折愈合,但是目前关于两者共同干预骨折愈合的研究较少,三七总皂苷可能通过在某段时间内促进浓缩生长因子相关因子的释放来达到加快骨折愈合的目的。目的:观察三七总皂苷对浓缩生长因子释放,以及对大鼠骨折愈合的影响。方法:8周龄SD大鼠18只,编号后随机分为三七总皂苷组、模型对照组以及空白组。三七总皂苷组给予三七总皂苷灌胃2周,模型对照组给予生理盐水2 mL灌胃2周,空白组正常饲喂。2周后三七总皂苷组与模型对照组同时采血离心获取浓缩生长因子备用,继续正常饲喂1周,然后对所有大鼠进行股骨骨折造模处理,三七总皂苷组与模型对照组植入自体浓缩生长因子,并用ELISA法检测1 h及1,3,5,7,9,11 d生长因子释放量;通过观察术后2个月X射线片及骨组织苏木精-伊红染色结果,评估骨折愈合情况。结果与结论:①生长因子释放情况:三七总皂苷组的血管内皮生长因子A和转化生长因子β在第7,9,11天的释放浓度高于模型对照组(P<0.05),血小板衍生生长因子BB在第5,9,11天的释放浓度高于模型对照组(P<0.05),碱性成纤维细胞生长因子在1-11天的释放浓度均高于模型对照组(P<0.05);②骨折愈合情况:术后2个月行X射线片检查,三七总皂苷组的骨折愈合情况优于模型对照组,两组均优于空白组;取材苏木精-伊红染色发现,三七总皂苷组成骨细胞生成量大于模型对照组,两组均大于空白组;③提示三七总皂苷可以上调浓缩生长因子相关因子的释放浓度,三七总皂苷干预后的浓缩生长因子对促进大鼠骨折愈合更有优势。