Bone Regeneration

骨再生
  • 文章类型: Journal Article
    单囊性成釉细胞瘤(UAM)的颌骨可以通过减压有效地减少体积,促进骨骼再生并恢复下颌对称性。这项研究定量评估了下颌骨UAM减压后下颌骨体积和对称性的变化。这项研究包括17例接受手术减压,然后进行第二阶段刮治的下颌UAM患者。收集术前、术后三维计算机断层扫描(CT)图像。测量骨体积和皮质穿孔面积以评估减压期间的骨生长。通过计算下颌骨两侧的体积比,分析下颌骨的体积对称性。在病变区域的表面上识别出十二对标志,它们的坐标用于计算下颌骨的平均不对称指数(AI)。采用配对t检验和Mann-WhitneyU检验进行统计分析。p<0.05被认为指示有统计学意义。平均减压时间为9.41±3.28个月。平均骨量增加8.07±2.41%,皮质穿孔恢复率为71.97±14.99%。下颌骨的体积对称性明显改善(p<0.05),并且观察到AI的统计学显着下降(p<0.05)。总之,UAM减压可促进下颌骨的骨骼生长和对称恢复。本评估技术在临床上可用于定量评估下颌不对称性。
    Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.
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  • 文章类型: Journal Article
    背景:在口腔颌面手术中优化愈合和骨修复过程的探索反映了临床实践中的不断发展,在对越来越令人满意的结果的需求以及减少术后并发症的需求的驱动下。
    目的:评价血小板和富含白细胞纤维蛋白(L-PRF)在口腔颌面手术中的愈合和骨修复过程中的作用。
    方法:本研究的系统综述方案包括研究问题的定义,研究的领域,数据库搜索,搜索策略,纳入和排除标准,要包括的研究类型,效果的措施,筛选的方法,数据提取和分析,以及数据综合的方法。在Cochrane数据库上进行了系统的文献检索,WebofScience,PubMed,ScienceDirect,Embase和谷歌学者。
    结果:数据库中的战略搜索确定了1,159项研究。用Rayyan©软件删除重复项后,仍然有946条。其中,30符合纳入标准。在根据纳入和排除标准进行仔细评估后,8项研究被认为是高度相关的,并包括在系统评价中。
    结论:血小板和白细胞丰富纤维蛋白(L-PRF)对口腔颌面手术的愈合过程和骨修复具有积极作用。
    BACKGROUND: The search to optimize the healing and bone repair processes in oral and maxillofacial surgeries reflects the constant evolution in clinical practice, driven by the demand for increasingly satisfactory results and the need to minimize postoperative complications.
    OBJECTIVE: To evaluate the efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing and bone repair process in oral and maxillofacial surgeries.
    METHODS: The systematic review protocol for this study included the definition of the research question, the domain of the study, the databases searched, the search strategy, the inclusion and exclusion criteria, the types of studies to be included, the measures of effect, the methods for screening, data extraction and analysis, and the approach to data synthesis. Systematic literature searches were carried out on Cochrane databases, Web of Science, PubMed, ScienceDirect, Embase and Google Scholar.
    RESULTS: The strategic search in the databases identified 1,159 studies. After removing the duplicates with the Rayyan© software, 946 articles remained. Of these, 30 met the inclusion criteria. After careful evaluation based on the inclusion and exclusion criteria, 8 studies were considered highly relevant and included in the systematic review.
    CONCLUSIONS: Platelet and Leukocyte Rich Fibrin (L-PRF) has a positive effect on the healing process and bone repair in oral and maxillofacial surgeries.
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  • 文章类型: Journal Article
    大约5%-10%的骨折继续延迟愈合和骨不连,构成显著的临床,经济,和社会挑战。涉及开放式骨收获和移植的当前治疗方法与供体部位的相当大的疼痛和潜在的发病率相关。因此,越来越多的人对微创方法感兴趣,如骨髓穿刺液浓缩物(BMAC),其中包含间充质基质细胞(MSC),巨噬细胞(Mφ),和T细胞。然而,在美国,使用培养或活化的细胞进行治疗尚未获得FDA批准,需要进一步探索有效骨形成的最佳细胞类型和比例。随着我们对骨免疫学的理解的进步,显然,来自抗炎Mφ(M2)的因子通过MSCs促进骨形成。此外,M2Mφ促进T辅助细胞2(Th2)和Treg细胞,两者都能促进骨骼形成。在这项研究中,我们调查了MSCs之间的相互作用,Mφ,和T细胞在骨形成中的作用,并探索了BMAC亚群的潜力。使用原代MSCs进行共培养实验,Mφ,和特定比例的CD4+T细胞。我们的结果表明,未活化的T细胞对MSCs的成骨没有直接影响,同时以1:5:10的比例将MSC与Mφ和T细胞共培养,对骨形成产生积极影响。此外,在共培养的早期,T细胞数量增加导致M2极化增加和Th2细胞比例增加。这些发现表明通过调节BMAC中的免疫和间充质细胞比率来增强骨形成的潜力。通过了解免疫细胞对骨形成的相互作用和影响,我们可以制定更有效的治疗骨缺损和骨不愈合的策略和方案.需要进一步的研究来研究这些体内相互作用,并探索影响基于MSC的治疗的其他因素。
    Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.
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  • 文章类型: Journal Article
    牙周炎是一种以牙周组织破坏为特征的炎症性疾病,促进骨组织再生是根治牙周炎的关键。补骨脂素是补骨脂的主要成分,并具有多种生物学效应,包括抗骨质疏松和成骨。我们构建了一种新型的装有补骨脂素(PSO)和基质细胞衍生因子-1(SDF-1)的水凝胶,用于直接内源性细胞归巢。本研究旨在评价PSO/SDF-1对牙周炎患者牙周骨再生的协同作用。CCK8、碱性磷酸酶(ALP)活性测定结果,和茜素红染色显示PSO/SDF-1联合处理促进细胞增殖,趋化能力,和PDLSCs的ALP活性。qRT-PCR和westernblotting显示碱性磷酸酶(ALP)的表达水平,矮相关转录因子2(RUNX2),骨钙蛋白(OCN)基因上调。建立大鼠牙周模型,观察局部应用复合水凝胶对骨再生的影响。这些结果证明PSO/SDF-1组合治疗显著促进新骨形成。免疫组化(IHC)结果证实ALP的表达升高,RUNX2和OCN成骨基因。PSO/SDF-1复合水凝胶可协同调节生物学功能,促进牙周骨形成。因此,本研究为牙周骨再生提供了新的策略。
    Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.
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  • 文章类型: Journal Article
    外伤导致的骨缺损,疾病或先天性异常对全球健康构成重大挑战。传统的治疗方法,如亲笔签名和同种异体移植有局限性,导致探索骨组织工程(BTE)作为一种替代方法。这篇综述旨在提供骨再生机制的全面分析,重点是基于壳聚糖的生物材料和间充质干细胞(MSCs)在BTE中的作用。此外,壳聚糖的理化和生物学特性,研究了其与其他材料结合后的骨再生潜力以及MSCs促进骨再生的机制。此外,研究了不同的支架开发方法和将MSCs掺入基于壳聚糖的支架中。壳聚糖具有显著的生物相容性,生物降解性和骨传导性,使其成为BTE的一个有吸引力的选择。诸如Runx2和Osterix的转录因子与诸如BMP和Wnt通路的信号通路之间的相互作用调节MSCs的分化和骨再生。各种形式的脚手架,包括多孔和纤维注射,在BTE中表现出了希望。壳聚糖和MSCs在BTE中的协同组合在解决骨缺损和促进骨再生方面具有重要的潜力,突出了骨缺损带来的临床挑战的前景。
    Bone defects resulting from trauma, illness or congenital abnormalities represent a significant challenge to global health. Conventional treatments such as autographs and allografts have limitations, leading to the exploration of bone tissue engineering (BTE) as an alternative approach. This review aims to provide a comprehensive analysis of bone regeneration mechanisms with a focus on the role of chitosan-based biomaterials and mesenchymal stem cells (MSCs) in BTE. In addition, the physiochemical and biological properties of chitosan, its potential for bone regeneration when combined with other materials and the mechanisms through which MSCs facilitate bone regeneration were investigated. In addition, different methods of scaffold development and the incorporation of MSCs into chitosan-based scaffolds were examined. Chitosan has remarkable biocompatibility, biodegradability and osteoconductivity, making it an attractive choice for BTE. Interactions between transcription factors such as Runx2 and Osterix and signaling pathways such as the BMP and Wnt pathways regulate the differentiation of MSCs and bone regeneration. Various forms of scaffolding, including porous and fibrous injections, have shown promise in BTE. The synergistic combination of chitosan and MSCs in BTE has significant potential for addressing bone defects and promoting bone regeneration, highlighting the promising future of clinical challenges posed by bone defects.
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  • 文章类型: Journal Article
    由生物活性玻璃(BAG)制造多孔组织工程支架由于BAG组合物在支架制造期间的热处理中结晶的倾向而变得复杂。这里,实验生物相容性玻璃S59(SiO259.7wt%,Na2O25.5wt%,CaO11.0wt%,P2O52.5wt%,B2O31.3wt%),已知抗结晶,用于将玻璃颗粒(300-500µm)烧结成多孔支架。然后在兔股骨中和在体外连续流动条件下(体外14天/体内56天)研究支架的溶解行为。支架在体内具有骨传导性,骨可以长入支架结构。尽管如此,支架不能诱导足够快速的骨向内生长以代替由于溶解而损失的强度。当支架颈部溶解时,支架失去其结构和强度。体外,S59在整个14天的实验中一致溶解,仅导致轻微的反应层形成。因此,制造保留其无定形结构的来自S59的BAG支架是可能的。支架的相对快速和稳定的溶解意味着玻璃S59可能具有用于提供初始强度和稳定的复合植入物的潜力。在更长的暴露时间内可预测的离子释放。
    Fabrication of porous tissue-engineering scaffolds from bioactive glasses (BAG) is complicated by the tendency of BAG compositions to crystallize in thermal treatments during scaffold manufacture. Here, experimental biocompatible glass S59 (SiO2 59.7 wt%, Na2O 25.5 wt%, CaO 11.0 wt%, P2O5 2.5 wt%, B2O3 1.3 wt%), known to be resistant to crystallization, was used in sintering of glass granules (300-500 µm) into porous scaffolds. The dissolution behavior of the scaffolds was then studied in vivo in rabbit femurs and under continuous flow conditions in vitro (14 days in vitro/56 days in vivo). The scaffolds were osteoconductive in vivo, as bone could grow into the scaffold structure. Still, the scaffolds could not induce sufficiently rapid bone ingrowth to replace the strength lost due to dissolution. The scaffolds lost their structure and strength as the scaffold necks dissolved. In vitro, S59 dissolved congruently throughout the 14-day experiments, resulting in only a slight reaction layer formation. Manufacturing BAG scaffolds from S59 that retain their amorphous structure was thus possible. The relatively rapid and stable dissolution of the scaffold implies that the glass S59 may have the potential to be used in composite implants providing initial strength and stable, predictable release of ions over longer exposure times.
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  • 文章类型: Journal Article
    骨移植物(BG)的部署对于大型骨缺损的支架引导骨再生(SGBR)的成功至关重要。因此,提供最大化自体移植物的成骨能力同时还最小化在收集期间的移植物损伤的收获装置是关键的。作为铰刀-冲洗器-抽吸器2(RIA2)系统的替代方案-当今骨科诊所中使用的大容量移植物收获的黄金标准-一种新颖的髓内BG收获概念已在临床前引入并称为ARA(抽吸器扩孔-抽吸)概念。ARA概念使用髓内内容物的抽吸,然后是髓内骨的髓扩孔抽吸。相对于RIA2系统,此概念允许对BG收获条件进行更大的定制。在成功的体外验证之后,我们假设ARA概念收集的BG与RIA2系统收集的BG相比具有相当的体内成骨能力.
    我们使用3D打印,医用级聚己内酯-羟基磷灰石(mPCL-HA,重量96%:4%)具有Voronoi设计的支架,装载或不装载不同的绵羊收获的BG,并在异位骨形成大鼠模型中测试它们长达8周。
    在整个支架-BG结构中观察到活跃的骨再生,特别是在具有软骨内骨形成的骨碎片的表面上,和高度血管化的组织在完全互连的孔隙结构内形成。来自RIA2系统的BG和ARA概念在新骨体积形成和压缩测试中没有差异(杨氏模量,p=0.74;屈服强度,p=0.50)。这些结果强调了装载有来自ARA概念的BG的mPCL-HAVoronoi支架和RIA2系统的成骨能力是等效的。
    总而言之,ARA概念为RIA2系统提供了一个有希望的替代方案,用于收集临床上整合到SGBR策略中的BG。
    我们的结果表明,装载有来自新型髓内收获概念的BG的可生物降解复合支架和RIA2系统具有等效的成骨能力。因此,创新,高度直观的髓内收获概念为RIA2系统提供了一个有希望的替代方案,用于收获骨移植物,这是SGBR概念常规转化为临床实践的重要组成部分。
    UNASSIGNED: The deployment of bone grafts (BGs) is critical to the success of scaffold-guided bone regeneration (SGBR) of large bone defects. It is thus critical to provide harvesting devices that maximize osteogenic capacity of the autograft while also minimizing graft damage during collection. As an alternative to the Reamer-Irrigator-Aspirator 2 (RIA 2) system - the gold standard for large-volume graft harvesting used in orthopaedic clinics today - a novel intramedullary BG harvesting concept has been preclinically introduced and referred to as the ARA (aspirator + reaming-aspiration) concept. The ARA concept uses aspiration of the intramedullary content, followed by medullary reaming-aspiration of the endosteal bone. This concept allows greater customization of BG harvesting conditions vis-à-vis the RIA 2 system. Following its successful in vitro validation, we hypothesized that an ARA concept-collected BG would have comparable in vivo osteogenic capacity compared to the RIA 2 system-collected BG.
    UNASSIGNED: We used 3D-printed, medical-grade polycaprolactone-hydroxyapatite (mPCL-HA, wt 96 %:4 %) scaffolds with a Voronoi design, loaded with or without different sheep-harvested BGs and tested them in an ectopic bone formation rat model for up to 8 weeks.
    UNASSIGNED: Active bone regeneration was observed throughout the scaffold-BG constructs, particularly on the surface of the bone chips with endochondral bone formation, and highly vascularized tissue formed within the fully interconnected pore architecture. There were no differences between the BGs derived from the RIA 2 system and the ARA concept in new bone volume formation and in compression tests (Young\'s modulus, p = 0.74; yield strength, p = 0.50). These results highlight that the osteogenic capacities of the mPCL-HA Voronoi scaffold loaded with BGs from the ARA concept and the RIA 2 system are equivalent.
    UNASSIGNED: In conclusion, the ARA concept offers a promising alternative to the RIA 2 system for harvesting BGs to be clinically integrated into SGBR strategies.
    UNASSIGNED: Our results show that biodegradable composite scaffolds loaded with BGs from the novel intramedullary harvesting concept and the RIA 2 system have equivalent osteogenic capacity. Thus, the innovative, highly intuitive intramedullary harvesting concept offers a promising alternative to the RIA 2 system for harvesting bone grafts, which are an important component for the routine translation of SGBR concepts into clinical practice.
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  • 文章类型: Journal Article
    红景天苷(SAL)是红景天最有效的成分,一种传统的中药。隐丹参酮(CT)是丹参的主要脂溶性提取物,在成骨方面表现出相当大的应用潜力。在这里,通过同轴静电纺丝成功制备了负载CT和SAL的聚己内酯/明胶纳米纤维膜(PSGC膜),并对其进行了表征。
    在本研究中采用了这种能够持续和控制药物释放的膜。将膜与骨髓间充质干细胞和人脐静脉内皮细胞共培养显示出优异的生物相容性,并表现出成骨和血管生成能力。此外,PSGC膜释放药物激活Wnt/β-catenin信号通路,促进成骨分化和血管化。评估膜的血管形成和成骨能力,涉及移植到大鼠皮下区域,并评估大鼠颅骨的骨再生缺损,分别。显微计算机断层扫描,组织学检查,免疫组织化学,和免疫荧光染色证实膜的突出血管生成能力术后两周,术后八周在大鼠颅骨缺损中观察到成骨的发生率较高。
    总的来说,SAL和CT加载的同轴电纺纳米纤维膜协同增强骨修复和再生。
    UNASSIGNED: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.
    UNASSIGNED: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane\'s vascularization and osteogenic capacities involved transplantation onto a rat\'s subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane\'s outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.
    UNASSIGNED: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.
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  • 文章类型: Journal Article
    背景:修复骨缺损仍然是一个主要的临床问题。构建含生长因子的骨组织工程,干细胞,支架材料修复骨缺损已成为近期研究的热点。神经生长因子(NGF)促进骨髓间充质干细胞(BMSCs)成骨,但是BMSCs在移植过程中的低存活率仍然是一个未解决的问题。在这项研究中,我们研究了过表达NGF的BMSCs通过抑制焦凋亡对骨缺损的治疗作用。
    方法:通过检测焦亡蛋白水平,探讨过表达NGF的BMSCs在骨折局部炎症中的低存活率与焦亡的关系。然后,NGF+/BMSCs-NSA-Sca骨组织工程是通过将过表达NGF的BMSCs接种在同种异体骨支架上,并添加焦亡抑制剂坏死磺酰胺(NSA)来构建的。通过显微CT研究了Sprague-Dawley(SD)大鼠的股骨髁缺损模型,组织学,体外和体内WB和PCR分析以评估骨修复的再生作用。
    结果:过表达NGF的BMSCs在成骨分化过程中发生的焦亡与神经生长因子受体(P75NTR)有关。此外,NSA可以阻断过表达NGF的BMSCs的焦亡。值得注意的是,使用临界大小股骨髁部缺损模型进行的分析表明,NGF+/BMSCs-NSA-Sca组显著抑制了骨功能恢复,并在缺损中具有更高的成骨作用.
    结论:NGF+/BMSCs-NSA在骨缺损修复中具有较强的成骨特性。此外,在这项研究中开发的NGF/BMSCs-NSA-Sca混合物为开发新的组织工程构建体开辟了新的视野。
    BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis.
    METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair.
    RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects.
    CONCLUSIONS: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.
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  • 文章类型: Journal Article
    背景:这项研究旨在鉴定有利于形成细胞可吸收纳米复合物的甘氨酸类似物,与BMP2联合增强胶原蛋白合成和随后的骨生成以改善骨再生。
    方法:在成骨条件下或使用BMP2,评估甘氨酸及其衍生物对MC3T3-E1细胞和人骨髓间充质干细胞(BMSCs)成骨分化的影响。通过碱性磷酸酶染色和实时定量聚合酶链反应(RT-qPCR)评估成骨分化。通过扫描电子显微镜检查纳米复合物的形成,圆二色性,和紫外可见光谱。使用小鼠颅骨缺损模型验证了体内成骨作用,骨再生通过显微计算机断层扫描和组织形态学分析进行评估。
    结果:甘氨酸,甘氨酸甲酯,和甘氨酰胺与成骨培养基(OSM)一起显着增强了胶原蛋白的合成和ALP活性。GA成为成骨细胞分化标记基因最有效的诱导物。将GA与BMP2组合协同刺激ALP活性和两种细胞系中成骨细胞标志物的表达。GA容易形成纳米复合物,通过强静电相互作用促进细胞摄取。在体内颅骨缺损小鼠模型中,GA和BMP2组合显示骨体积增加,骨体积/组织体积比,骨小梁数,与其他组合相比,成熟的骨形成。
    结论:GA和BMP2通过纳米复合物的形成协同促进体外成骨细胞分化和体内骨再生。这种组合对患有骨缺损的个体具有治疗前景,展示其临床干预的潜力。
    BACKGROUND: This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration.
    METHODS: Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis.
    RESULTS: Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations.
    CONCLUSIONS: GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.
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