富血小板血浆在骨愈合治疗中的作用

背景：富血小板血浆可明显促进各种组织的修复和愈合。临床上运用其治疗骨软骨以及软组织缺损等骨科疾病方面已取得了很多成果。 目的：简要综述近年来富血小板血浆相关研究,总结其在骨科基础研究与临床应用中的进展。 方法：以“platelet-rich plasma, bone formation, tissue engineering”为检索词,检索Pubmed数据库(1999-01/2011-01),以“富血小板血浆,骨缺损,组织工程”为检索词,检索中国期刊全文数据库(1999-01/2011-01)。纳入与干细胞以及干细胞在骨科应用方面的基础和临床研究,排除不相关及重复研究。计算机初检得到301篇文献,根据纳入排除标准,最终纳入62篇。 结果与结论：尽管目前还存在争论,但富血小板血浆仍是一种非常有潜力的技术,尤其是作为细胞支架在组织工程中的应用如能被进一步研究证实有效,将对骨组织工程乃至其他各种组织工程研究产生重大的影响。因此除了规范研究在循证医学方面的要求之外,这应该是富血小板血浆今后研究的有一个重要方向。     

富血小板血浆促进骨修复的机制及应用

背景：目前普遍认为富血小板血浆具有促进骨修复的作用,但其具体机制尚未完全阐明,富血小板的最佳应用方式仍不明确。 目的：综述近期富血小板血浆促进骨修复机制及应用的研究进展。 方法：由第一作者检索1995/2011 PubMed与CNKI数据库有关富血小板血浆促进骨修复机制及应用的相关文献,排除与研究目的相关性差及内容陈旧、重复的文献。中文关键词为“富血小板血浆,生长因子,骨修复”,英文关键词为“Platelet-rich plasma,Growth factor,Bone repair”。共纳入25篇符合标准的文献进行综述。 结果与结论：富血小板血浆含有多种高浓度生长因子,普遍的观点认为聚合过程中血小板脱颗粒释放多种生长因子联合作用加速了骨修复的过程。单独应用富血小板血浆对骨修复的治疗效果不如与其他物质复合使用效果明显。     

富血小板纤维蛋白在口腔医学研究中的相关进展北大核心

背景:富血小板纤维蛋白是第二代血小板浓缩物,近年来广泛应用于口腔医学领域。但目前仍无确凿的证据解释其对促进软硬组织愈合保存的影响。目的:针对当前富血小板纤维蛋白在口腔医学的研究概况做一综述。方法:设计综述的撰写结构,检索中国知网和PubMed数据库2001-2021年相关文献,检索词为“Platelet-rich fibrin,Stomatology”“富血小板纤维蛋白,口腔医学”,部分经典文献延长检索时间限制,分析所得文献的摘要及内容,通过纳入和排除得到相关文献,对53篇符合标准的文献进行综述。结果与结论:尽管有文献证实,富血小板纤维蛋白在口腔疾病中对于软硬组织的修复重建有着良好的效果,但是目前的证据并不能明确解释其相关机制。加之富血小板纤维蛋白的制备方法目前还不尽相同,有着种类繁多的富血小板纤维蛋白衍生物以及不同离心方式,因此仍需要大量实验做进一步研究。     

富血小板血浆满足不同类型关节软骨损伤的治疗需求

背景：关节软骨属于透明软骨,自我修复能力差,传统疗法只能使缺损处再生出纤维软骨,无法彻底修复关节软骨缺损,故需一种可以再生出透明软骨的疗法修复缺损。根据关节软骨的缺损深度、部位以及是否伴随炎症可将关节软骨缺损分类,不同类型的关节软骨缺损有不同的致病机制与治疗策略。富血小板血浆作为富含各种生长因子的自体血小板衍生物被广泛应用于关节软骨缺损的治疗,并且已被大量研究证明对多种类型关节软骨缺损均有较好的治疗效果。就目前而言,富血小板血浆疗法有望治愈关节软骨缺损。目的：总结富血小板血浆的制备、储存以及激活方式,分析富血小板血浆所具性质是否满足不同类型关节软骨缺损的治疗需求,综述富血小板血浆对不同类型关节软骨缺损的治疗作用。方法：检索Pub Med、Web of Science、中国知网数据库,中文检索词为“富血小板血浆,关节软骨,制备,机制,软骨缺损”,英文检索词为“platelet-rich plasma,articular cartilage, prepraration, mechanism, full-thickness cartilage defect,osteochondral def...     

富血小板血浆临床应用及其生物材料性能

背景：富血小板血浆的制备方法、设备及应用手段等方面有了长足发展,但是相对于国内临床工作者而言富血小板血浆技术仍是一项相对较新的生物技术。 目的：对富血小板血浆分类等相关概念和存在问题加以说明和论述,使其制备和应用技术等更加清晰和明确。 方法：以“platelet rich plasma,preparation,富血小板血浆,制备”为检索词,检索PubMed数据库及维普数据库1995-09/ 2010-09相关文章。 结果与结论：根据所含白细胞的多少可以将富血小板血浆分为贫白细胞的富血小板血浆和富白细胞的富血小板血浆;根据应用形式又可以分为未激活富血小板血浆和激活的富血小板血浆,后者又可以分为富血小板血浆凝胶和富血小板血浆释放物。被视为第二代血小板浓缩物的富血小板纤维蛋白与富血小板血浆都含有高浓度的血小板,但两者在制备方法,凝胶形成方式等方面有根本的区别。由于其安全性和易于制备,富血小板血浆在医学领域的应用将会越来越多,但临床应用还要保持谨慎,因为富血小板血浆在多个方面还缺乏相关研究。     

血小板凝胶的制备方法及其影响因素

背景：血小板凝胶制备方法繁多,分类标准不统一。 目的：总结血小板凝胶制备方法,并讨论影响因素。 方法：由第一作者检索1990至2011年 PubMed数据库及万方数据库。英文检索词为“Platelet gel,Classification,Parameters”,中文检索词为“血小板凝胶,分类,影响因素”。 结果与结论：依据凝胶产量与成分、凝胶中纤维蛋白结构两个主要影响因素可将血小板凝胶制备方法分为4大类,即纯富血小板血浆凝胶、富白细胞-血小板血浆凝胶、纯富血小板纤维蛋白凝胶和富白细胞-血小板纤维蛋白凝胶;根据制备流程不同,血小板凝胶的每一种制备方法还可以再分为手工制备方法和全自动制备方法,但各种分类方法均存在不足之处。     

血小板裂解液在骨组织工程中的应用

 背景：以血小板裂解液修复骨缺损不仅去除了残余细胞结构,降低了免疫原性,而且还保留了其中的多种生长因子,可为异体或异种移植创造条件。 目的：总结归纳有关对能促进骨生长的血小板裂解液相关研究及应用方式进行综述。 方法：以“tissue engineering, bone defect, gene therapy, growth factor”为检索词,检索PubMed数据库(2004-01/2011-01),以“血小板血浆,骨组织工程,血小板裂解液,生长因子”为检索词,检索CBM数据库(2004-01/2011-01)。文献检索语种为英文和中文。纳入血小板裂解液促进骨的再生和修复的文献,排除重复文献。 结果与结论：计算机初检得到340篇文献,根据纳入排除标准,对其中23篇文献进行分析。目前研究证实,血小板裂解液可促进骨髓基质干细胞和成骨细胞的增殖;与生物陶瓷或自体骨复合,可明显促进骨缺损的修复。合理应用血小板裂解液对骨的再生和修复具有重要意义。关键词：血小板裂解液;成骨细胞;骨缺损;细胞生长因子;骨组织工程 doi:10.3969/j.issn.1673-8225.2012.20.041     

Choukroun富血小板纤维蛋白复合自体微小颗粒骨修复兔颅骨缺损

背景：Choukroun富血小板纤维蛋白与自体微小颗粒骨具有促进骨缺损修复的能力,但单独应用均有其不足,拟将两种材料结合使用以期达到理想效果。 目的：观察Choukroun富血小板纤维蛋白复合自体微小颗粒骨修复颅骨缺损的效果。 方法：采用自体对照方法在大耳白兔颅骨中缝两侧利用磨骨术各制备标准一致的骨缺损,即刻于一侧骨缺损处回填Choukroun富血小板纤维蛋白膜与自体微小颗粒骨混合物作为实验组,另一侧只填充Choukroun富血小板纤维蛋白膜作为对照组,术后4,6,8周行软X射线摄片与组织病理切片观察。 结果与结论：实验组骨小梁面积显著大于对照组,骨愈合程度均优于对照组,骨小梁密度、形态、新生骨质的量及结构、成骨细胞数量均优于对照组(P < 0.05或P < 0.01),说明Choukroun富血小板纤维蛋白与自体微小颗粒骨复合材料较Choukroun富血小板纤维蛋白具有更明显促进骨缺损修复的作用。     

运用富血小板血浆或富血小板纤维蛋白与传统的血凝块作为支架重建牙髓血运比较的Meta分析

目的:评价牙髓血运重建时运用富血小板血浆（PRP）或富血小板纤维蛋白（PRF）同传统的血凝块（BC）作为支架哪种材料效果更佳。方法:检索PubMed、Embase、Cochrane、Web of Science、中国期刊全文数据库（CNKI）和万方数字期刊全文数据库,检索时间截止到2020年8月。通过RevMan 5....     

浓缩红骨髓/富血小板纤维蛋白复合载自体骨膜碎片修复下颌骨缺损

背景：富血小板纤维蛋白支架结构有利于红骨髓中间充质干细胞及各种生长因子的生长,促进最终成骨。 目的：探讨浓缩红骨髓/富血小板纤维蛋白复合载自体骨膜碎片支架材料修复兔下颌骨缺损的可行性。 方法：制备新西兰大白兔双侧下颌骨人工制备骨缺损模型,采用自身对照方法,左侧为实验侧,植入自体浓缩红骨髓/富血小板纤维蛋白复合载自体骨膜碎片与纳米羟基磷灰石支架材料;右侧为对照侧,植入自体骨膜碎片复合纳米羟基磷灰石支架材料。术后2,4,8,12周制备组织标本,行大体观察、影像学分析、苏木精-伊红染色、扫描电镜检测。 结果与结论：影像学检查及组织学染色显示,实验侧骨缺损处愈合程度、成骨速度及质量明显优于对照侧;扫描电镜显示实验侧复合材料与组织相容性好,无炎症刺激反应;牙CT分析数据及新骨形成情况分别证明实验侧骨密度CT值显著高于对照侧(P < 0.05),实验侧新生骨面积显著高于对照侧(P < 0.05)。表明浓缩红骨髓/富血小板纤维蛋白复合载自体骨膜碎片支架材料具有明显骨诱导作用,可望成为临床应用中修复颌骨缺损的新型材料。     

Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs

Background: For the sake of reducing post extraction resorption, getting optimal positioning of the implant and shortening treatment time, immediate implant placement following tooth extraction has been proposed as a treatment option. However, the large bone defect peri-implant has a negative influence on the process of bone healing. In this study, umbilical cord mesenchymal stem cells (UCMSCs) were transplanted into the bone defect peri-implant inbeagle dogs and the effect of UCMSCs on bone regeneration in peri-implant were assessed. Methods: The mandibular second, third and fourth premolars of 8 beagle dogs were extracted bilaterally. The defects in one side were filled with platelet-rich fibrin (PRF) and then UCMSCs were injected into the defect area, while the defects in the other side were filled with PRF only as control group. The titanium implant was placed into the distal root socket of each extracted tooth. The animals were sacrificed at week 2, 4 and 8 post operative. The bone defects adjacent to the implant which are 4 mm in height, 4 mm in the mesio-distal direction and 3.5 mm in the bucco-lingual direction were made after immediate implant. Histomorphometric analysis was performed using methylene blue-fuchsin acid staining and hematoxylin and eosin (HE) staining to evaluate bone regeneration. Results: The direct bone-to-implant contact (BIC) in the experiment after 4 and 8 weeks was 56.47±1.18% and 76.23±2.08%; and in the control group was40.79±0.65% and 61.17±2.79%, respectively. The percentage of newly formed bone after 2, 4 and 8 weeks was 17.60±1.5%, 49.82±4.02% and 67.16±2.1% in experiment group; and in control group 14.30±1.25%, 37.04±2.29% and 58.83±3.36%, respectively. These results represented significant differences statistically. Conclusion: Intra-bone marrow injection of UCMSCs can promote new bone formation. UCMSCs can be used to as excellent seed cells to repair the large defect peri-implant after immediate implant.     

富血小板纤维蛋白骨诱导动物模型的建立

BACKGROUND: At present, many studies have focused on platelet-rich fibrin combined with other bone substitute materials in repair of peri-implant bone defects and sinus lifting, but there is still a lack of research  about the platelet-rich fibrin alone in repair of critical-size bone defects. OBJECTIVE: To compare the effect of three kinds of bone substitutes, platelet-rich fibrin, Bio-Oss bone substitute and autogenous cancellous bone, in repair of bone defects. METHODS: Four areas of cylindrical critical bone defects with a diameter of 6.0 mm and depth of 10.0 mm were prepared in the medial femoral condyle of beagle dogs. Three areas of bone defects were implanted with autologous platelet-rich fibrin, Bio-Oss bone substitutes and autologous cancellous bone, respectively. The remaining one area of bone defect was not implanted any substance, as control group. X-ray and Micro-CT detections in bone defect area were conducted after 12 weeks of surgery. RESULTS AND CONCLUSION: (1) X-ray: the density of platelet-rich fibrin group was more higher, but still slightly lower than that of the surrounding normal bone tissue; the density of the Bio-Oss bone substitute group was more lower, but still higher than that of the surrounding bone tissues; the density of autologous cancellous bone group was more higher, which was close to that of the surrounding bone tissues; circular low-density images were visible in the control group. (2) Micro-CT: platelet-rich fibrin group was similar with the autogenous cancellous bone group, and their density was slightly lower than that of the surrounding normal bone tissues; the trabecular bone exlibited a clear regular arrangement, and no obvious interface; the Bio-Oss bone substitute group showed a high density image with clear interface; the bone defect area was still clearly visible in the control group, with a low-density image. The bone volume fraction and trabecular number in the platelet-rich fibrin and autologous cancellous bone groups were both higher than those in the Bio-Oss bone substitute group (P < 0.05). These results demonstrate that platelet-rich fibrin and autogenous cancellous bone have a similar bone repair effect.      

富血小板纤维蛋白新生诱导骨的组织学观察

BACKGROUND: In previous experiments, we have confirmed that platelet rich fibrin has the ability of osteoinduction, and have conducted a preliminary study on its microstructure and biomechanics. However, little is reported on its histology research. OBJECTIVE: To compare the histological changes after implanting platelet-rich fibrin, Bio-Oss and autologous bone and to analyze the pros and cons of platelet-rich fibrin implantation for repair of bone defects. METHODS: As previously reported, animal models of critical bone defects were established respectively on the bilateral femoral condyles of 12 beagle dogs. Then, platelet-rich fibrin, Bio-Oss+collagen membrane (Bio-Oss group) and autologous bone (autologous bone group)+collagen membrane were respectively implanted. At 3, 6, 8 and 12 months, one experimental dog from each group was killed, respectively, and histological observation was performed. Another beagle dog as blank control was enrolled to establish the animal model of critical bone defects, with no implantation. RESULTS AND CONCLUSION: At 3, 6, 8 and 12 months after implantation, there were significant differences in the new bone formation speed and amount between the platelet-rich fibrin group, Bio-Oss group and autologous bone group. These three kinds of bone grafts all had osteoinductive ability to different extents. In the platelet-rich fibrin group, the osteogenic effects were better at 3 and 6 months, and the new bone was similar to natural one; in the autologuos bone group, bone necrosis was noticeable at 3 and 6 months, but the osteogenic effects became better at 8 months, and the new bone was similar to natural one at 12 months; in the Bio-oss group, the osteogenic effects were similar to those in the platelet-rich fibrin group, but the residual of Bio-oss was visible at 12 months; in the blank control group, no bone formed at 3 months, indicating the animal model of critical bone defects was made successfully. In brief, the platelet-rich fibrin has good osteoinductive ability, with shorter time and better quality.       

Platelet-rich fibrin as a material for alveolar ridge preservation significantly reduces the resorption of alveolar bone height and width after tooth extraction: A meta-analysis北大核心

OBJECTIVE: At present, platelet-rich fibrin is widely used in site retention after tooth extraction, but the effect of platelet-rich fibrin in alveolar ridge preservation is not very clear compared with other materials. This study evaluated the effect of applied platelet-rich fibrin in the preservation of alveolar ridge after tooth extraction to provide theoretical basis for clinical application of platelet-rich fibrin to reduce alveolar bone resorption. METHODS: Up to June 2020, all clinical randomized controlled studies on platelet-rich fibrin for alveolar ridge preservation, including platelet-rich fibrin alone and platelet-rich fibrin combined with heterogeneous bone, were collected by using The Cochrane Library, PubMed, Web of science core set, EMbase, CNKI, and Wanfang databases. Two researchers extracted data from the retrieved documents and used Cochrane bias risk assessment tools to evaluate the bias risk included in the study. RevMan 5.3 software was used for meta-analysis. RESULTS: (1) Totally 159 articles were retrieved, and 11 randomized controlled trials were finally included, involving 531 patients and 575 implants. (2) The results of meta-analysis showed that the difference in the height absorption of tooth alveolar bone was not statistically significant when platelet-rich fibrin was applied alone (SMD=-0.38, 95%CI:-0.83 to-0.06, P > 0.05). There were significant differences between platelet-rich fibrin composite heterogeneous bone and simple xenogeneic bone in alveolar bone resorption height (3 months: SMD=-1.40, 95%CI:-1.79 to-1.01, P < 0.05; 6 months: SMD=-1.37, 95%CI:-1.68 to-1.06, P < 0.05), alveolar bone resorption width at 3 and 6 months after tooth extraction (SMD=-0.18, 95%CI:-0.25 to-0.11, P < 0.05), and mouth mucosa healing rate at 2 weeks after tooth extraction (SMD=9.90, 95%CI:8.61-11.19, P < 0.05). CONCLUSION: Applying platelet-rich fibrin composite heterogeneous bone after tooth extraction can remarkably reduce the resorption of alveolar bone both in height and width and accelerate soft tissue healing. Because of the small sample size included in the study, clinical studies with a large sample size are needed to verify the above conclusions. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

多孔羟基磷灰石与富血小板血浆和纤维蛋白胶复合修复骨缺损

背景：自体骨移植是治疗骨缺损的最理想方法,但来源有限,供区有一定的并发症,所以寻找自体骨的替代材料一直是骨科学领域的研究方向。 目的：观察珊瑚多孔羟基磷灰石、富血小板血浆和纤维蛋白胶复合物修复骨缺损的效果。 方法：在新西兰大白兔双侧前臂桡骨中段截骨1.5 cm制成骨缺损模型,随机分为3组,实验组植入珊瑚多孔羟基磷灰石、富血小板血浆和纤维蛋白胶复合物,对照组植入自体骨,空白对照组未植入任何物质。 结果与结论：①X射线：实验组术后12周时骨缺损基本修复,塑性完全,愈合过程与对照组同步;空白对照组骨缺损无明显变化。②组织病理学：实验组与对照组术后12周时骨缺损基本修复,出现成熟板层骨及哈佛氏管;空白对照组仅见大量成纤维细胞增生,未见骨质形成。③生物力学：术后2周时实验组最大扭矩和抗扭刚度优于对照组(P < 0.05),术后12周时两组最大扭矩和抗扭刚度差异无显著性意义。表明珊瑚多孔羟基磷灰石、富血小板血浆和纤维蛋白胶复合物具有促骨质愈合的作用,甚至在术后早期修复骨缺损的效果优于自体骨。     

Enzymatically induced mineralization of platelet-rich fibrin

Membranes of the autologous blood-derived biomaterial platelet-rich fibrin (PRF) were functionalized by incorporation of alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, and subsequently incubated in calcium glycerophosphate (CaGP) solution to induce PRFs mineralization with calcium phosphate (CaP) to improve PRFs suitability as a material for bone replacement. Incorporated ALP retained its bioactivity and induced formation of CaP material within PRF membranes, as confirmed by SEM, EDS, FTIR, and von Kossa staining. The mass percentage attributable to CaP was quantified by lyophilization and measurement of the remaining mass fraction as well as by TGA. Cytocompatibility tests (LDH, MTT, and WST) with SAOS-2 cells showed that mineralized PRF did not release substances detrimental to cell vitality. Live/dead staining and SEM showed that mineralized PRF was colonized by cells. The results show that hydrogel biomaterials such as PRF can be mineralized through functionalization with ALP.     

Mathematical model of the coagulation in the bone-dental implant interface

The healing of the injured tissues after the insertion of a dental implant begins with the formation of a fibrin clot that detains the blood flow and gives initial support to the osteoprogenitor cells. The adequate formation of this clot determines the direct and stable connection between bone and implant, process known as osseointegration. The aim of this work is to introduce a mathematical model of the coagulation in the bone-dental implant interface based on two reaction-diffusion equations representing the kinetic reaction that leads to the production of fibrin and a transformation equation representing the formation of the fibrillar network compounding the clot. The model also includes a parameter associated to the blood platelets concentration that extends the model framework to the analysis of two hematological disorders well reported: thrombocytosis and thrombocytopenia. The solution of the model is performed using the finite element method, obtaining as results the distribution of spatial-temporal patterns in the bone-dental implant interface. These results are in qualitative concordance with experimental results previously reported by other authors. Although the model is a simplified version of the biological process of coagulation, the results here obtained justify the mathematical formulation implemented. It is concluded that the model can be used as a methodological basis for the formulation of a general model of the osseointegration in the bone-dental implant interface.