Analysis on the hotspot of the platelet-rich plasma based on VOSviewer

doi:10.3969/j.issn.2095-4344.1737

Abstract

Abstract:

BACKGROUND: Platelet-rich plasma is a platelet concentrate obtained from autologous whole blood after centrifugation, which contains a lot of growth factors and proteins. Activated platelets can release a variety of growth factors so as to accelerate cell proliferation and differentiation, and can effectively promote tissue repair. Platelet-rich plasma has been widely used in various clinical fields because of its convenient sampling and simple preparation. Overseas research on platelet-rich plasma has been carried out for a long time, and has achieved certain results.

OBJECTIVE: To review the research advance of platelet-rich plasma at abroad in recent 5 years.

METHODS: PubMed database was retrieved with the keywords of “plasma, platelet-rich, platelet rich plasma, platelet-rich plasma’’ and the retrieval time was from 2014-2018. The visual tool VOSviewer was used to deeply search the title information of the papers retrieved. The annual and national published number, and research topics were discussed. The knowledge map generated by software is used to visually display the hotspot of platelet-rich plasma research at abroad.

RESULTS AND CONCLUSION: Thirty-eight relevant articles were retrieved. The results show that in the past five years the number of papers published on platelet-rich plasma in foreign countries has increased year by year, and the United States has the largest number of publications. Through co-word clustering analysis, the hotspots of platelet-rich plasma are mainly concentrated on the following five aspects: animal experiments, orthopedics, cytology experiments, stomatology and chronic wounds. Research results provide reference for the direction and hotspot of research on platelet-rich plasma in China.

Key words: platelet-rich plasma, clustering;, VOSviewer;, knowledge mapping, bibliometrics, co-word clustering analysis, orthopedics, stomatology, chronic wounds

CLC Number:

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R453

R364

Cite this article

Wang Haijiao, Huang Ruina, Wang Xiaojun, Zheng Bili, Chen Peina, Zeng Xiujuan. Analysis on the hotspot of the platelet-rich plasma based on VOSviewer[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(18): 2947-2952.

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Figures/Tables 5

2.1 文献发表年代分布文章检索得到2014年至2018年的相关文献3 246篇，近5年相关文献发表数量见表1，由于2018年文献仅检索到10月31日，故统计的2018年文献数量仅为前10个月，富血小板血浆技术近5年发文数量保持持续增长趋势，2017年文献数量最多，为749篇。"

2.2 文献发表国家分布截至2018-10-31，PubMed数据库检索结果显示，近5年发表富血小板血浆相关研究文献的有27个国家，其中美国发表文献数量最多，为1 355篇，占41.7%，中国发文量排名第8位，发文量排名前10位的多为欧美国家，详见表2。"

2.3 富血小板血浆研究热点主题分析关键词是一篇文章内容的浓缩，通过对关键词进行分析，我们能够掌握研究领域的发展趋势与研究热点。通过VOSviewer对富血小板血浆领域关键词进行统计，设定频次大于等于10次为高频关键词，建立共词矩阵并绘制关键词共现网络图谱，文章列举前30个高频关键词，见表3。"

通过VOSviewer进行共词聚类分析，采用“标签视图(Label View)”进行共词聚类展示。在标签视图中，每1个节点代表1个关键词或术语，其出现频次越高节点越大，1个颜色代表1个聚类，聚类是由共现频次高的关键词或者术语构成，图中的连线代表连接的2个关键词至少有1次共现在1篇文献里，关键词共现频次越高线越粗。列举每个聚类中的关键词，并归纳总结主题，5个聚类分别为：#1动物实验；#2骨关节科；#3细胞学实验；#4口腔科；#5慢性伤口，详见表4，图1。 2.3.1 富血小板血浆在动物实验的应用动物实验主要用来构建疾病模型，用以探究富血小板血浆对实验动物损伤治疗效果及最佳浓度，也为细胞学实验提供组织来源。动物实验可以模拟真实情况开展腱骨愈合、关节损伤、移植反应、生物力学、创面愈合等不可替代的实验。富血小板血浆在治疗骨关节科、口腔科、慢性伤口、皮肤问题等领域的实验动物模型研究中显示了明确的效果。Szponder等[6]将富血小板血浆联合β-磷酸三钙治疗动物粉碎性骨折，观察到超过91%的动物出现骨愈合，富血小板血浆联合β-磷酸三钙能有效治疗动物粉碎性骨折。Badis等[7]在成年雄绵羊背部建立创伤模型，对创面进行形态学测量和组织病理学检查，研究富血小板血浆对损伤皮肤的治疗作用，结果显示在术后第3天富血小板血浆可减轻创面炎症反应，第3周能有效促进上皮化，加快创面愈合。Yang等[8]研究富血小板血浆对犬牙周组织再生根面愈合的影响，发现在犬牙再植过程中牙根表面应用富血小板血浆可减少牙槽骨粘连促进牙骨质样组织形成形成。也有学者研究富血小板血浆联合骨髓间充质干细或者其他生物组织成分的治疗效果，均取得一定积极作用，但是，也存在部分动物实验治疗效果不佳，这为未来的动物实验提出更高的要求，以保证实验结果的真实可靠可重复。 2.3.2 富血小板血浆在骨与关节科领域的应用目前，富血小板血浆在骨关节科广泛应用，如骨折难愈合、股骨头坏死、肌肉、肌腱韧带损伤及骨性关节炎等多个领域。富血小板血浆促进骨愈合的机制是血小板联合纤维蛋白在骨愈合炎症阶段形成血肿，同时分泌丰富的细胞因子活化骨痂形成期的信号通路，研究表明富血小板血浆能促进成骨，提高新生骨质量。庞伟峰等[9]研究者发现接受富血小板血浆治疗的16例骨折不愈合患者在平均10.38个月后随访，均无发生脱钉及内固定物断裂等不良反应，获得骨性愈合。 Zhang等[10]研究富血小板血浆对兔缺血性股骨头坏死区域血管生成及成骨相关因子的影响，发现富血小板血浆能促进成骨细胞相关因子和血管生成相关因子的表达，降低血液黏度、血浆黏度及红细胞聚集性，从而修复局部血管，改善该区域的血液供应，促进成骨细胞分化以及骨形成，加速坏死骨组织的修复与愈合。姜良斌等[11]将富血小板血浆加高位股骨头颈开窗植骨支撑术应用于早期股骨头坏死的治疗中，观察到与单纯头颈开窗植骨支撑治疗组相比，富血小板血浆组术后6个月股骨头外形良好，无变形无坍塌，股骨头密度增加，疼痛目测类比评分下降，髋关节Harris评分提高，说明富血小板血浆能减轻早期股骨头坏死患者髋关节疼痛，促进骨组织修复，改善关节功能。富血小板血浆能够增强肌卫星细胞活化，加粗再生肌纤维直径，促进肌生成，刺激成肌蛋白表达，使肌肉愈合增快[12]。Wetzel等[13]做了回顾性队列研究观察富血小板血浆治疗腿后群肌损伤效果，对比15例保守治疗失败后接受富血小板血浆治疗的患者与未做富血小板血浆治疗的患者，治疗前后两组患目测类比疼痛评分、数字疼痛评分及恢复体育锻炼情况均明显改善，但最终结果组间无显著差异。有学者提出富血小板血浆未见明显起效可能是由于给药延迟及剂量少，因为富血小板血浆中的生物活性因子有浓度依赖性特点，且在损伤后数小时促进肌肉、血管及纤维组织生成，数小时后损伤微环境中的富血小板血浆生物靶标消失或表型转变[14]，故富血小板血浆治疗肌肉损伤效果还有待研究。目前已有运动员接受富血小板血浆治疗，Vetrano等[15]研究富血小板血浆疗法与体外冲击波疗法治疗髌骨肌腱炎效果比较，经过1年随访发现富血小板血浆治疗髌骨肌腱炎的中期疗效优于体外冲击波疗法。其他学者发现富血小板血浆对多种肌腱韧带损伤均能起到一定治疗作用，但也有学者发出相反的声音[16]。富血小板血浆治疗骨关节炎效果仍然存在争议，Say等[17]将90例轻中度骨关节炎患者随机分为富血小板血浆组和透明质酸组，随访时间为3，6个月，发现富血小板血浆组患者骨关节炎评分、疼痛视觉模拟评分明显优于透明质酸组。另外一项随机对照试验发现富血小板血浆能明显改善轻度关节退变，但对于中度骨关节炎治疗效果与透明质酸对比无统计学差异[18]。鉴于富血小板血浆对骨关节炎的治疗效果可能与注射剂量、技术、关节病变程度和部位等有关，故富血小板血浆对骨关节炎的疗效有待确认，目前未推荐富血小板血浆为骨关节炎治疗一线方案。富血小板血浆在骨关节科领域的应用日益增多，在国内外研究中临床疗效较好与无效的报道均存在，临床治疗效果较好的报道中，多数样本量较小，大样本文章中临床疗效很好的较少，故暂时没有足够的证据证明富血小板血浆在临床的有效性。富血小板血浆的应用仍然存在许多问题需要探讨，如富血小板血浆的最佳制备方法及最适宜的浓度、适应证及禁忌证等，未来需要开展样本量较大、设计严谨的随机对照试验来判断富血小板血浆的临床效果。 2.3.3 富血小板血浆在细胞学实验的应用细胞学实验是将富血小板血浆应用到临床试验的研究基础，国内外已有多位学者研究富血小板血浆对骨骼肌细胞、软骨细胞、腱细胞、骨髓间充质干细胞及脂肪间充质干细胞的作用[19-23]。富含血小板血浆(富血小板血浆)和间充质干细胞是肌肉骨骼再生的重要工具，部分学者称富血小板血浆能促进间充质干细胞增殖分化，也有学者提出富血小板血浆起到的是抑制分化的作用[24]。有研究发现不同血小板浓度的富血小板血浆对间充质干细胞的增殖和分化具有不同的影响，生长因子在富血小板血浆诱导间充质干细胞分化的过程中起重要作用，这表明制备浓度适宜的富血小板血浆可能是改善基于间充质干细胞的组织再生的重要方法[25]。将富血小板血浆应用于组织工程材料是近年的一个研究热点，其作为细胞支架将会是未来研究的重要方向。关于富血小板血浆的作用机制、适宜浓度、制备方法等研究有在细胞学实验上开展，目前，已有学者研究富血小板血浆联合其他药物或生物材料的治疗效果。 2.3.4 富血小板血浆在口腔科领域的应用 Marx等[26]于1988年用富血小板血浆复合自体松质骨治疗颌骨缺损，发现富血小板血浆能加快骨组织形成速率，其认为凝血酶激原和钙离子等激活富血小板纤维蛋白，释放丰富的生长因子，促进组织修复。近年来富血小板血浆在口腔医学领域的多个方面得到运用，如骨组织重建、种植体周围骨缺损修复、口腔颌面软组织创伤修复及牙周组织再生等。种植手术后常发生种植体周围炎等不良反应，通常表现为种植体周围骨缺损。胡秋斌等[27]研究者将富血小板血浆联合Bio-Gide人工骨粉应用于种植体周围骨量修复，治疗后4月将骨组织标本行组织学观察，得出富血小板血浆组种植体周围新骨密度较对照组高。牙周炎发生时，牙槽骨因为局部刺激出现吸收大于再生，使牙周支持组织丧失，牙齿松动脱落。植骨有助于牙周组织生理形态及功能的恢复。钱文慧等[28]用富血小板血浆混羟基磷灰石治疗20例中度及重度慢性牙周炎患者的牙周骨缺损；术后3，6个月观察牙周各项指标，判断牙周骨高度及密度改变发现：富血小板血浆组在术后3个月明显优于对照组，而牙龈退缩、临床附着水平、探诊深度及手术后6个月牙周再附着没有明显差异。 2.3.5 富血小板血浆在慢性伤口领域的应用慢性伤口主要包括压疮、糖尿病足、动静脉溃疡、放射性溃疡以及各类外伤，由于创面长期不愈合，内部耐药菌多，换药治疗效果不佳，给患者带来巨大的痛苦及沉重的经济负担，由于伤口存在影响患者出行，就诊时多需家属陪护，给家属的工作生活带来一定的影响。慢性伤口迁延不愈的原因主要有：①伤口感染或坏死组织滞留；②伤口局部微循环差，血管功能不全；③生长因子活性减弱、数量减少及调节失控；④修复细胞过度凋亡，生长因子与受体间应答障碍[29]。富血小板血浆中富含多种生长因子，如血小板衍生生长因子、表皮生长因子、转化生长因子及血管内皮生长因子等。富血小板血浆用于慢性伤口，能给慢性伤口床提供活性高、数量多的生长因子，有助于伤口床血管再生，重建局部血液循环；生长因子与胞膜上的受体结合能促进修复细胞分化增殖；富血小板血浆能激活成纤维细胞，使白细胞、中性粒细胞及巨噬细胞等向伤口床迁移，清除细菌，有效控制局部感染[30-32]。有研究分别发现富血小板血浆在体外能够抑制大肠杆菌、金黄色葡萄球菌等细菌生长[32]。目前富血小板血浆在体内的具体抗菌机制仍未明确，但对不同细菌及真菌的一系列体外抗菌试验表明其确有抗菌作用。富血小板血浆技术最开始就是用来治疗各种伤口的愈合，研究发现富血小板血浆能促进损伤组织愈合。近年来关于富血小板血浆治疗慢性伤口的临床试验及动物、细胞学实验都取得明显效果。Çetinkaya等[33]研究富血小板血浆治疗多重耐药细菌感染创面的效果，体外实验发现富血小板血浆能有效抑制耐甲氧西林金黄色葡萄球菌、肺炎克雷伯菌和铜绿假单胞菌等细菌的生长。有研究在马小腿的慢性伤口中应用富血小板血浆，发现伤口局部的上皮细胞增殖加快，血液循环改善[34]。付德丰等[35]用富血小板血浆治疗126例慢性难愈合性伤口患者，发现富血小板血浆能改善患者伤口愈合效果，促进软组织伤口修复，效果显著。术后由于伤口过度收缩形成瘢痕，严重影响面部手术后的美观，有研究发现皮肤缝合应用富血小板血浆能加速皮肤愈合，减少瘢痕组织形成。慢性伤口给医护人员及患者带来很大的困扰，用富血小板血浆能促进软组织修复，加快伤口愈合，减少瘢痕，减轻疼痛。目前富血小板血浆在国外已被广泛应用于整形外科和难愈性创面领域。 "

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[1]	Jiang Hongying, Zhu Liang, Yu Xi, Huang Jing, Xiang Xiaona, Lan Zhengyan, He Hongchen. Effect of platelet-rich plasma on pressure ulcers after spinal cord injury [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(8): 1149-1153.
[2]	He Xiangzhong, Chen Haiyun, Liu Jun, Lü Yang, Pan Jianke, Yang Wenbin, He Jingwen, Huang Junhan. Platelet-rich plasma combined with microfracture versus microfracture in the treatment of knee cartilage lesions: a meta-analysis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(6): 964-969.
[3]	Wu Zijian, Hu Zhaoduan, Xie Youqiong, Wang Feng, Li Jia, Li Bocun, Cai Guowei, Peng Rui. Three-dimensional printing technology and bone tissue engineering research: literature metrology and visual analysis of research hotspots [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 564-569.
[4]	Shi Xiaoxiu, Mao Shilong, Liu Yang, Ma Xingshuang, Luo Yanfeng. Comparison of tantalum and titanium (alloy) as orthopedic materials: physical and chemical indexes, antibacterial and osteogenic ability [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 593-599.
[5]	Lu Yuyun, Huang Mei, Shi Xinlei, Chen Baoyan. Bibliometric and visualization analysis of breast cancer stem cell literature from 2011 to 2020 based on Web of Science database [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 4001-4008.
[6]	Fan Jin, Zeng Luyao, Zhong Dongling, Li Yuxi, Tian Yanping, Huang Yijie, Jin Rongjiang. Development of functional near-infrared spectroscopy in recent 10 years: a visual analysis using CiteSpace [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(23): 3711-3717.
[7]	Yang Qin, Zhou Honghai, Chen Longhao, Zhong Zhong, Xu Yigao, Huang Zhaozhi. Research status and development trend of pelvic reconstruction techniques: a bibliometric and visual analysis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(23): 3718-3724.
[8]	Huang Maomao, Hu Yue, Wang Binchuan, Zhang Chi, Xie Yujie, Wang Jianxiong, Wang Li, Xu Fangyuan. Bibliometric and visual analysis of international literature addressing ischemic stroke rehabilitation in recent 10 years [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(23): 3725-3733.
[9]	Gan Lili, Xiong Na, Liu Yanfei. Hydrogel as drug scaffold in skin wound repair: challenges of clinical application possibilities [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(22): 3578-3583.
[10]	Ren Wenbo, Liao Yuanpeng. Visualization analysis of traumatic osteoarthritis research hotspots and content based on CiteSpace [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(21): 3374-3381.
[11]	Pan Xuan, Zhao Meng, Zhang Xiumei, Zhao Jie, Zhai Yunkai. Research and application of biological three-dimensional printing technology in the field of precision medicine: analysis of Chinese and English literature [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(21): 3382-3389.
[12]	Wei Jinqiang, Huang Dengcheng, Cao Xuewei, Zhou Jianwei, Sun He, Li Zehui. Analysis of researches on TCM treatments for cartilage diseases in recent 20 years by mapping knowledge domains [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(20): 3202-3209.
[13]	Zuo Xiuqin, Yin Sasa, Xie Huimin, Jia Zishan, Zhang Lining. Applicability and specifications of platelet-rich plasma in musculoskeletal repair [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(20): 3239-3245.
[14]	Jing Jinpeng, Zhang Yue, Liu Xiaomin, Liu Yi. Buyang Huanwu Decoction in prevention of deep venous thrombosis after orthopedic surgery: meta-analysis and trial sequential analysis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(20): 3267-3274.
[15]	Zhang Kai, Zhang Xiaobo, Shi Jintao, Wang Keping, Zhou Haiyu. Mesenchymal stem cells for treatment of intervertebral disc degeneration: a bibliometric and visualization analysis based on Web of Science database [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(19): 3031-3038.