纤维蛋白胶在胸外科手术中的应用

目的：了解纤维蛋白胶在胸外科手术中应用的效果。方法：在手术中将纤维蛋白胶喷至漏气、渗血、血管残端和支气管残端等处。结果：所有患者均未出现不良反应；术后平均漏气天数为0．14d，平均第1天引流量为273．5m1，平均第2天引流量为164.4ml，平均拔管时间为2．09d，术后胸管引流通畅未发现因蛋白胶脱落所致的胸管堵塞；所有患者均未发生术后局部感染；远期随访无支气管胸膜瘘发生。结论：纤维蛋白胶在胸外科领域有很好的应用前景。     

Barium-impregnated fibrin glue: application to a bleeding duodenal sinus

A 64-year-old man with Crohn's disease who had undergone repair of an ileovesical fistula and ileoileostomy had numerous postoperative complications related to sepsis and wound healing. Subsequently, upper gastrointestinal bleeding developed, and the site was identified as a duodenal sinus. Medical management was unsuccessful in controlling the bleeding. Because of the considerable risk associated with reoperation in this seriously ill patient, approval was obtained from the Food and Drug Administration to use fibrin glue in an attempt to prevent further bleeding. The glue was mixed with barium and placed in the duodenal sinus under endoscopic guidance. The barium-impregnated glue facilitated follow-up surveillance with abdominal roentgenography. The patient had no further gastrointestinal bleeding. Further clinical and experimental studies should be conducted to determine the mechanism of action and the efficacy of this application of fibrin glue.     

Controlled collagen crosslinking process in tissue‐engineered fibroblast sheets for preventing scar contracture on the surface of lungs

For preventing the scar contracture of host tissue and adjusting the tensile strength of covering cell sheets, a controlled collagen crosslinking step process in the preparation of skin‐fibroblast sheets for repairing wound was investigated by using β‐aminopropionitrile (BAPN), a collagen crosslinking inhibitor, in the culture medium. Skin fibroblasts obtained from neonatal rats were cultured in medium with and without 0.25 mm BAPN for 7 days and seeded on temperature‐responsive culture dishes. After the confluent cells were non‐invasively harvested as a monolithic cell sheet, two cell sheets were transplanted to a lung‐injury site of athymic rats, which was closed by neither fibrin glue nor suturing. Four weeks after the transplantation the animals were sacrificed and the lungs with the transplanted cell sheets were examined. Although the control cell sheet‐transplanted lungs contracted the surrounding tissue, BAPN‐treated cell sheet‐transplanted lungs showed no contraction of the tissue. Collagen fibres of control cell sheets were more dense and thick than those of BAPN‐treated cell sheets, where the crosslinking of collagen fibres was clearly inhibited. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) showed that BAPN‐treated cell sheets gave no β‐chain band, indicating that the collagen crosslinkings of the fibroblast sheets were able to be controlled by BAPN. BAPN‐treated fibroblast sheets promise to allow wound clefts to be repaired without scar contractures. Copyright © 2012 John Wiley & Sons, Ltd.     

Factor V inhibitor after injection of human thrombin (tissucol) into a bleeding peptic ulcer

Endoscopic injection of fibrin glue into a bleeding peptic ulcer is an effective and safe treatment modality. The present report describes a patient who developed rectal bleeding from an arteriovenous malformation after endoscopic injection of fibrin glue containing human thrombin into a gastric ulcer. Additional laboratory investigations revealed the presence of an inhibitor against coagulation factor V, which resulted in severe coagulopathy, triggering the bleeding. Acquired factor V inhibitors have frequently been reported with the use of bovine thrombin, but to our knowledge, they have never been documented in patients exposed to human thrombin. Endoscopists should be aware of this rare, but potentially serious, complication.     

Wound healing effect of autologous fibrin glue and polyglycolic acid sheets in a rat back skin defect model

Fibrin glue from autologous plasma may prevent viral infection and allergic reaction. Moreover, this biomaterial contains growth factors such as TGF-β and VEGF that promote reconstruction of the mucous membrane by stimulating fibroblast proliferation and angiogenesis. Thus, autologous fibrin glue is predicted to improve healing better than commercial fibrin glue. Here, we evaluated the effects of autologous fibrin glue on the crucial early phase of wound healing. Epithelial defects were introduced in rats and covered with polyglycolic acid (PGA) sheets with or without commercial or autologous fibrin glue. Wound healing was assessed for six weeks by histology and immunohistochemistry. Our results demonstrate that wounds covered with PGA sheets and autologous fibrin glue achieved efficient wound healing without complications such as local infection or incomplete healing. The rate of recovery of the regenerating epithelium in this group was superior to that in wounds covered with PGA sheets and commercial fibrin glue. Immunohistochemistry of laminin, cytokeratin, and VEGF confirmed fine and rapid epithelial neogenesis. Collectively, our results indicate that covering surgical wounds with autologous fibrin glue promotes wound healing and epithelialization, improves safety, and reduces the risks of viral infection and allergic reaction associated with conventional techniques.     

纤维蛋白胶在骨科中的应用

背景:纤维蛋白胶是一种生物蛋白制剂,由纤维蛋白原、凝血酶及其他生物活性因子组成,具有止血、趋化及促细胞有丝分裂等特性,有着良好的生物相容性。目的:对纤维蛋白胶在骨科的应用进行综述。方法:以"fibringlue,biomaterial,application"为英文检索词,以"纤维蛋白胶,骨科,应用"为中文检索词,检索PubMed、BP、SD、万方及维普等数据库1995-01/2011-05相关文献,选取纤维蛋白胶在骨科中的应用有关文献30篇进行总结。结果与结论:纤维蛋白胶是一种具有多向生物活性的生物蛋白,能迅速形成立体网状结构,起到良好的止血作用。在注射部位局部形成凝胶圈,起封闭与粘合作用。具有预防脊柱手术后硬脊膜外腔粘连,抑制局部炎症扩散,减轻水肿压迫,促进术后切口愈合的作用。能充当生物基质,应用于骨或软骨组织工程。     

生物止血材料在妇产科手术中的应用

背景：良好的生物敷料或纱布可直接促进凝血过程,不仅可用于广泛渗血创面,且在一些常用的妇产科手术中能有效降低渗血率。目的：评价不同生物止血敷料及纱布的材料学性能及应用于妇产科切口的生物相容性,寻找符合不同切口创面需要的止血材料。方法：采用电子检索的方式,在万方数据库（http：//www.wanfangdata.com.cn/）中检索1999-01/2011-04有关妇产科生物止血材料应用的研究文章,关键词为＂妇产科,生物材料,止血敷料,纱布,胶原/壳聚糖＂,排除重复研究、普通综述或Meta分析类文章,筛选纳入30篇文献进行评价。结果与结论：近几年国内外生物医用可吸收止血材料主要包括纤维蛋白胶、壳聚糖、明胶海绵、氰基丙烯酸酯类组织胶、氧化纤维素和氧化再生纤维素等。各种止血性伤口急救材料都有各自的特点,但在妇产科应用的选择上,应考虑多方面因素,包括手术部位、出血部位、切口形态大小、不同渗/出血情况的填塞要求、不同止血材料的自身性能及与机体的相容性等。但因目前尚无完全符合理想标准的材料,因此开发新的快速止血和与宿主相容性良好的止血材料及复合材料势在必行。     

纤维蛋白胶介导内皮祖细胞再生心肌梗死血管的可行性

背景：有研究显示纤维蛋白胶可促进成肌细胞移植物的保持和生存,减少梗死范围并在梗死区诱导新生血管化。目的：了解内皮祖细胞经可降解材料纤维蛋白胶移植到大鼠梗死心肌后的血管再生情况。方法：将27只SD大鼠随机均分为3组,非心肌梗死组9只、心肌梗死即刻移植组9只与心肌梗死1周移植组9只。每个大组又再分为两个亚组,即移植人脐带源内皮祖细胞-纤维蛋白胶复合物的实验组与移植纤维蛋白胶的对照组。移植后3,8周处死,通过显微镜、免疫组织化学和心脏超声观察其在梗死心肌的血管再生和心功能改善情况。结果与结论：显微镜观察到,实验组大鼠心脏和胸部之间有一些疏松的结缔组织,而其与对照组之间无明显差异。组织和免疫学观察发现,各实验组和对照组的心脏结构不易区分且相对正常,未发现血管瘤、血管畸形和肿瘤等。血管测量结果显示实验组和对照组之间,以及各实验组之间均无差异,并且实验组和对照组之间心功能检查也没有统计学意义。此次研究内皮祖细胞结果没有阳性表现,将修改并提高细胞通过纤维蛋白基质传递的方法策略,确信细胞传递系统提供的有益性和有效性将会进一步得到证实。     

可吸收材料生物蛋白胶及明胶海绵在肝部分切除的应用

背景：生物蛋白胶广泛应用于各种外科手术中对富含小血管创面渗血的处理。目的：通过在肝部分切除中应用组织可吸收性医用生物蛋白胶,分析其对手术时间及肝部分切除后止血效果的影响。方法：对42例肝部分切除患者随机等分为实验组和对照组。实验组在肝部分切除后,缺损处喷洒医用生物蛋白胶封闭,并以明胶海绵剪成多块小片段混合医用生物蛋白胶以覆盖断面来代替常规缝合断面。对照组仅缝合收拢肝组织缺损。结果与结论：实验组使用的生物蛋白胶可迅速附着于创面,实验组患者肝部分切除的手术时间、出血量、引流量及渗血持续时间均明显小于对照组（P〈0.05）,且2组患者的住院天数和住院费用的差异无显著性意义（P〉0.05）。提示在肝部分切除中应用医用生物蛋白胶可以在不增加患者费用及住院时间的同时,有效降低手术时间、减少肝部分切除后出血。     

纤维蛋白胶外支架转染PCNA基因反义寡核苷酸预防移植静脉再狭窄

背景：前期研究成果,纤维蛋白胶不仅是一种良好的非限制性、生物可降解血管外支架,能够预防移植静脉内膜和中膜增生,而且是一种良好的药物缓释系统,能够提高血管外膜基因转染效率。目的：验证应用纤维蛋白胶外支架转染PCNA基因反义寡核苷酸预防移植静脉再狭窄的作用。方法：建立兔颈外静脉颈总动脉旁路移植模型,随机分为模型组、纤维蛋白胶支架组、纤维蛋白胶联合反义PNCA组。后两组分别给予纤维蛋白胶和纤维蛋白胶与携带PCNA反义寡核苷酸腺病毒的混合物于静脉桥外周均匀喷洒。结果与结论：移植后第28天模型组静脉移植物内膜和中膜增生明显,纤维蛋白胶外支架组静脉移植血管内膜和中膜增生程度明显减少（P〈0.01）,纤维蛋白胶联合反义PNCA组内膜和中膜增生程度明显少于纤维蛋白胶外支架组（P〈0.05）。纤维蛋白胶联合反义PNCA组PCNA基因mRNA及蛋白表达明显减少纤维蛋白胶外支架组（P〈0.05）,纤维蛋白胶外支架组表达明显弱于模型组（P〈0.05）。提示血管外膜反义PCNA转染可进一步抑制移植静脉管壁PCNA表达,纤维蛋白胶外支架联合反义PCNA对移植静脉内膜和中膜增生有协同抑制作用。     

Ulcers and nonvariceal bleeding

Although peptic ulcer continues to be the commonest cause of acute upper gastrointestinal bleeding, obscure haemorrhage from the Dieulafoy malformation and haemobilia must be considered, and may be amenable to endoscopic therapy. The patients who are at the highest risk of rebleeding and death are elderly, in shock at presentation, and have major stigmata of recent haemorrhage (SRH). The endoscopist must identify SRH, and identification may be made easier by washing the area with hydrogen peroxide. The natural history of SRH has been defined. There is wide interobserver variation in the interpretation of SRH, and there is probably therefore little value in the endoscopist describing subtle appearances. Although the value of endoscopic haemostatic therapy is established, it has still not been taken up by all institutions. Endoscopic injection of fibrin glue into the bleeding ulcer is a logical and relatively easy approach, and a systematic histological study of resected ulcers has shown that this does not adversely affect the ulcer healing process. Thermal therapies such as argon plasma coagulation and the heater probe have comparable efficacy. Although a combination of injection and thermal treatments may be logical, there are only trends suggesting that this is better than monotherapy. Nevertheless, the gold probe continues to be used in clinical practice. Experiments in an animal model of gastric bleeding suggest that the gold probe is effective, and that the version with a wide-gauge needle is best. Haemoclips may stop acute upper gastrointestinal bleeding from a range of sources. Patients who rebleed after initial endoscopic haemostasis have a tenfold increase in the risk of death. An important study from Hong Kong suggests that repeat endoscopic treatment after rebleeding has comparable morbidity and mortality to a policy of urgent surgery without endoscopic repeat intervention.     

内镜下喷洒生物蛋白胶治疗非曲张静脉性上消化道出血的临床应用

目的 探讨内镜下喷洒生物蛋白胶在非曲张静脉性上消化道出血中的意义。方法 对50例非曲张性上消化道出血患者,进行内镜下喷洒生物蛋白胶。结果 50例患者中有47例止血成功,有效率94％,有3例止血无效,均为喷射性出血。结论 内镜下注射生物蛋白胶适用于小静脉出血及毛细血管渗血,但对于小动脉和中等静脉出血止血效果差,该方法具有操作方便,疗效确切,价格低廉等特点。     

Practical hints for hemostasis in laparoscopic surgery.

With the developments achieved in recent years in laparoscopic surgery, the field has acquired a host of new techniques to achieve haemostasis, allowing the surgeon to tackle complex procedures. These techniques include physical modalities (as simple as compression or suturing and as sophisticated as endovascular staples), thermal modalities (such as bipolar coagulation, laser or ultrasonic dissectors), and topical sealants (e.g. Fibrin glue or gelatine matrix). It is up to the laparoscopic surgeon to be familiar with all these different modalities and their proper use and limitations. It should also be kept in mind that the best approach to haemostasis in laparoscopy is prevention by thorough case preparation and meticulous dissection technique. We herein expose an overview of the available techniques to achieve haemostatic control in laparoscopic surgery in the emergency as well as the elective setting. Representative surgeries are used for illustrative purposes to describe special manoeuvres.     

不同强度纤维蛋白胶作为免骨髓基质细胞培养支架材料的比较

背景:骨组织工程的支架材料主要作用为模拟细胞体内生长的空间环境,为细胞形成骨组织提供三维支架载体,但目前尚缺乏理想载体材料.目的:应用纤维蛋白胶作为细胞支架进行兔骨髓基质细胞立体培养,探讨其作为骨组织工程支架材料的可行性.设计、时间及地点:单一样本观察,于2007 09/2008 01在吉林大学中日联谊医院及天津科技大学机械工程学院完成.材料:将纤维蛋白原和凝血酶按不同比例混合,制备不同强度的纤维蛋白胶.1月龄雄性新两兰大耳白兔1只,体质量0.25 kg.方法:以兔骨髓基质细胞作为种子细胞在CO2孵箱中进行传代培养后,收集扩增的骨髓基质细胞与支架材料纤维蛋白胶复合后再进行培养4周.主要观察指标:采用相筹显微镜观察纤维蛋白胶中培养的骨髓基质细胞的生长状况,以苏木精伊红染色观察不同时期纤维蛋白胶中骨髓基质细胞的活性,以电子显微镜观察培养4周后骨髓皋质细胞超微结构变化.结果:骨髓基质细胞在不同强度的纤维蛋白胶中的牛长状态不同,在低强度纤维蛋白胶中活性好,扩增迅速,而在高强度纤维蚩白胶中细胞生长缓慢,数量少或逐渐死亡.电镜观察纤维蛋白原和凝血酶比例为4:1的纤维蛋白胶培养4周的基质细胞,各细胞器清晰可见,细胞具有良好活性.结论:骨髓基质细胞在低强度形成固体时的纤维蛋白胶中能够良好扩增生长,以纤维蛋白原和凝血酶比例为4:1的效果最佳.     

Fibrin Glue to Treat Spinal Fluid Leaks Associated with Intrathecal Drug Systems

Intrathecal drug delivery systems (IDDSs) are used to treat resistant pain states as well as intractable spasticity via medication delivery into the spinal fluid. Risks associated with implantation of these devices include infection, bleeding, intrathecal granuloma formation, and neurologic sequelae similar to other neuraxial procedures. Intrathecal catheter placement creates the additional risk of persistent spinal fluid leak, which can lead to postdural puncture headaches as well as seroma formation and may require subsequent surgical exploration or explantation. This retrospective case series examines 3 patients at a single institution with persistent spinal fluid leak after IDDS placement (and explantation in one case) resulting in headache and/or seroma formation that were treated with epidural fibrin glue. Three patients underwent IDDS implantation with baclofen for spasticity. In 1 patient, a cerebral spinal fluid leak developed at 1‐week postoperatively. After several unsuccessful epidural blood patches and surgical exploration with a catheter revision, she was ultimately treated successfully with a fibrin glue patch. The second patient received an IDDS and did well until a seroma developed 1 year later. He was likewise treated with an epidural fibrin glue patch after 2 failed blood patches. In a third patient, a spinal fluid leak developed after explantation of an IDDS and was treated with an epidural fibrin glue patch as initial therapy.     

纤维蛋白胶复合骨形态发生蛋白2塑形Bio-oss修复下颌骨缺损

背景：Bio-oss的颗粒状结构通常应用于洞形缺损的充填性移植,对于三壁以上的缺损修复难以成形。目的：评价Bio-oss以纤维蛋白胶复合骨形态发生蛋白2作为赋形材料后的成骨性能。方法：拔除9条杂种犬双侧下颌第2,4前臼齿及第2臼齿,造成1cmxlcm的骨缺损区,将Bio．OSS＋纤维蛋白胶＋骨形态发生蛋白2、Bio-oss＋纤维蛋白胶及Bio-oss材料分别植入第2,4前臼齿及第2臼齿骨缺损区。结果与结论：各组软组织均一期愈合。Bio-oss复合纤维蛋白胶后,骨粉结合紧密,不易剥离。术后4,8,12周时Bio-oss＋纤维蛋白胶＋骨形态发生蛋白2组新生骨百分率均高于其他两组（P〈0．05）。表明纤维蛋白胶的加入可以解决Bio-oss成形困难的问题,骨形态发生蛋白2的加入可促进成骨效果。     

Fibrin glue mixed with platelet-rich fibrin as a scaffold seeded with dental bud cells for tooth regeneration

Odontogenesis is a complex process with a series of epithelial‐mesenchymal interactions and odontogenic molecular cascades. In tissue engineering of teeth from stem cells, platelet‐rich fibrin (PRF), which is rich in growth factors and cytokines, may improve regeneration. Accordingly, PRF was added into fibrin glue to enrich the microenvironment with growth factors. Unerupted second molar tooth buds were harvested from miniature swine and cultured in vitro for 3 weeks to obtain dental bud cells (DBCs). Whole blood was collected for the preparation of PRF and fibrin glue before surgery. DBCs were suspended in fibrin glue and then enclosed with PRF, and the DBC‐fibrin glue‐PRF composite was autografted back into the original alveolar sockets. Radiographic and histological examinations were used to identify the regenerated tooth structure 36 weeks after implantation. Immunohistochemical staining was used to detect proteins specific to tooth regeneration. One pig developed a complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum, blood vessels, and periodontal ligaments in indiscriminate shape. Another animal had an unerupted tooth that expressed cytokeratin 14, dentin matrix protein‐1, vascular endothelial growth factor, and osteopontin. This study demonstrated, using autogenic cell transplantation in a porcine model, that DBCs seeded into fibrin glue‐PRF could regenerate a complete tooth. Copyright © 2011 John Wiley & Sons, Ltd.     

生物蛋白胶胸骨内注射治疗老年骨质疏松冠状动脉搭桥后的胸骨出血

背景：目前临床多应用创面涂抹方式发挥医用生物蛋白胶的止血作用,但骨腔内注射应用报道少见。目的：观察胸骨内注射生物蛋白胶对老年严重骨质疏松冠状动脉搭桥患者正中开胸出血的效果。方法：将48例体外循环下行正中开胸冠状动脉搭桥手术的75岁以上的严重骨质疏松患者随机数字表法分成实验组和对照组。实验组胸骨腔内注射生物蛋白胶,对照组常规涂抹医用骨蜡,记录两组术后12h引流量及总引流量、拔引流管时间及术后胸骨切口愈合情况。结果与结论：实验组术后12h引流量和总引流量、拔引流管时间及平均住院时间均较对照组明显减少（P〈0.05）,两组术后持续发热时间、术后胸骨感染裂开情况无明显差异。对照组术后胸骨切口感染裂开1例,实验组未发现不良反应。说明胸骨内注射生物蛋白胶能减少老年严重骨质疏松患者体外循环冠状动脉搭桥手术胸骨出血,减少出血相关并发症,不影响胸骨愈合。     

Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood

The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization.     

Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects

OBJECTIVE: Impairment of haemostasis has been described with slowly degradable medium molecular weight hydroxyethyl starch (MMW-HES), whereas rapidly degradable MMW-HES is generally considered to have no important effects on blood coagulation. This study was undertaken to investigate the effects of a rapidly degradable MMW-HES plasma substitute on primary haemostasis and blood coagulation in human subjects. DESIGN: Randomised, cross-over study. SETTING: Research unit of a university hospital. PARTICIPANTS: Nine healthy, adult male volunteers. INTERVENTIONS: A 60-min intravenous infusion of 1 l HES 200/0.5/6 (HAES-steril 6%) or 4% albumin (control). MEASUREMENT AND RESULTS: The infusion of HES resulted in decreased circulating levels of von Willebrand factor antigen (from 85+/-8% to 59+/-6% after HES vs from 80+/-7% to 69+/-8% after albumin, p<0.05) and ristocetin cofactor activity (from 93+/-4 to 67+/-4% after HES vs from 79+/-5 to 75+/-5% after albumin, p<0.01). This was associated with an impairment of in vitro platelet function as determined with the PFA-100 platelet function analyser (closure time with collagen/epinephrine from 120+/-7 to 159+/-14 s after HES vs from 121+/-7 to 137+/-10 s after albumin, p<0.05; with collagen/ADP from 88+/-3 to 116+/-9 s and from 103+/-4 to 114+/-7 s after HES and albumin, respectively, p=0.01). CONCLUSIONS: The infusion of 1 l of HES 200/0.5/6 in healthy human subjects results in moderately decreased plasma levels of von Willebrand factor associated with impairment of platelet function.