Fibrin Tissue Sealant as an Adjunct to Cleft Palate Repair.
Wu, Robin; Wilson, Alexander; Travieso, Roberto; Steinbacher, Derek M
2017-07-01
Fibrin glue is a common tissue sealant used to promote hemostasis, adhere tissues, and accelerate healing. Cleft palate repair can be technically challenging, creating dead space between tissue planes, and can be prone to complications such as would dehiscence or bleeding. The purpose of this study is to assess the role of fibrin glue as an adjunct to cleft palate repair. The authors hypothesize a beneficial impact on complication rates, including bleeding, dehiscence, and fistula formation, among others. Primary cleft palate repairs using fibrin glue were retrospectively analyzed. Demographic, intraoperative, perioperative, and postoperative data were combed for outcome variables. Complication rates were calculated in percentages and the results were compared to the published literature. Z-test statistics were performed for comparison. A total of 45 patients, 21 females and 24 males, who underwent primary cleft palate repair with fibrin glue between 2011 and 2014, had sufficient data to be reviewed. There were no instances of bleeding, dehiscence, airway obstruction, infection, oronasal fistula, or return to the operating room in any patients. One patient exhibited mild postoperative coughing and secretions that resolved with conservative measures. Another patient displayed postoperative seizure activity due to a pre-existing condition. All complication rates in our fibrin glue series were lower than those reported without the use of fibrin glue. Overall complication rates with fibrin sealant are significantly lower than overall complication rates without. Our data suggest that fibrin sealant is a beneficial adjunct to cleft palate repair. Its application is well-tolerated and the complication profile in our cohort was much less than the reported rates. The results of this preliminary study should be vetted with a prospective analysis involving a control group.
Fibrin Glue Improves the Therapeutic Effect of MSCs by Sustaining Survival and Paracrine Function
Kim, Inok; Lee, Sung Koo; Yoon, Jung In; Kim, Da Eun
2013-01-01
Fibrin glue has been widely investigated as a cell delivery vehicle for improving the therapeutic effects of mesenchymal stem cells (MSCs). Implanted MSCs produce their therapeutic effects by secreting paracrine factors and by replacing damaged tissues after differentiation. While the influence of fibrin glue on the differentiation potential of MSCs has been well documented, its effect on paracrine function of MSCs is largely unknown. Herein we investigated the influence of fibrin glue on the paracrine effects of MSCs. MSCs were isolated from human adipose tissue. The effects of fibrin glue on survival, migration, secretion of growth factors, and immune suppression of MSCs were investigated in vitro. MSCs in fibrin glue survived and secreted growth factors such as the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) over 14 days. VEGF and immune modulators, including the transforming growth factor (TGF)-β1 and prostaglandin E2, secreted from MSCs in fibrin glue significantly increased under inflammatory conditions. Thus, MSCs in fibrin glue effectively suppressed immune reactions. In addition, fibrin glue protected the MSCs from oxidative stress and prevented human dermal fibroblast death induced by exposure to extreme stress. In contrast, MSCs within fibrin glue hardly migrated. These results suggest that fibrin glue may sustain survival of implanted MSCs and their paracrine function. Our results provide a mechanistic data to allow further development of MSCs with fibrin glue as a clinical treatment. PMID:23701237
Fibrin glue inhibits migration of ocular surface epithelial cells
Yeung, A M; Faraj, L A; McIntosh, O D; Dhillon, V K; Dua, H S
2016-01-01
Purpose Fibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro. Methods Corneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed. Results Explants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14–16 for explants with fibrin glue. Conclusions Fibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy. PMID:27367746
Kouketsu, Atsumu; Nogami, Shinnosuke; Yamada-Fujiwara, Minami; Nagai, Hirokazu; Yamauchi, Kensuke; Mori, Shiro; Miyashita, Hitoshi; Kawai, Tadashi; Matsui, Aritsune; Kataoka, Yoshihiro; Satomi, Norihisa; Ezoe, Yushi; Abe, Satoko; Takeda, Yuri; Tone, Takeshi; Hirayama, Bunnichi; Kurobane, Tsuyoshi; Tashiro, Kazuki; Yanagisawa, Yuta; Takahashi, Tetsu
2017-09-01
The CryoSeal ® FS System has been recently introduced as an automated device for the production of complete fibrin glue from autologous plasma, rather than from pool allogenic or cattle blood, to prevent viral infection and allergic reaction. We evaluated the effectiveness of complete autologous fibrin glue and polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery. Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding were evaluated in 12 patients who underwent oral (including the tongue) mucosa excision, and received a PGA sheet and an autologous fibrin glue covering. They were compared with 12 patients who received a PGA sheet and commercial allogenic fibrin glue. All cases in the complete autologous fibrin glue group demonstrated good wound healing without complications such as local infection or incomplete cure. All evaluated clinical measures in this group were similar or superior to the commercial allogenic fibrin glue group. Coagulation and adhesion quality achieved with this method was comparable to that with a PGA sheet and commercial fibrin glue. Covering oral surgery wounds with complete autologous fibrin glue produced by an automated device was convenient, safe, and reduced the risk of viral infection and allergic reaction associated with conventional techniques. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Nakamura, T
1992-07-01
The possibility of repairing the defect of the pars interarticularis (pars defect) with Bone Morphogenetic Protein (BMP) and fibrin glue was studied. The pars defect established in the 5th lumbar vertebra of Wistar rat was treated with surgical implantation of a composite consisting of BMP, fibrin glue and autologous cancellous bone. At 3, 6, 9 and 12 weeks after implantation, the osteoinductive activity in the pars defect was observed histologically and compared with that of other composite implants such as BMP with fibrin glue, autologous cancellous bone alone and autologous cancellous bone with fibrin glue. Although perfect bone fusion was not obtained with any of the composites employed, a significant increase in bone formation was seen in a composite of BMP, fibrin glue and autologous cancellous bone (p less than 0.01) as compared with that seen in the others. Consequently, implantation of BMP and fibrin glue combined with some biomaterials which support osteo-induction of BMP and stabilize the pars defect might be successfully applied to repair the pars defect.
2014-01-01
Background Autologous transplantation of modified mesenchymal stem cells (MSCs) is a promising candidate for the treatment of the refractory clinical disease, avascular necrosis of the femoral head (ANFH). Our previous attempts by compounding MSCs with medical fibrin glue to treat ANFH in animal model have achieved excellent effects. However, the underlying molecular mechanism is unclear, especially on the transgenic gene expression. Methods Rabbit MSCs were isolated and compounded with fibrin glue. Following degrading of fibrin glue, proliferation, viability, expression of transgenic hepatocyte growth factor gene as well as osteogenic differentiation of MSCs were evaluated together with that of uncompounded MSCs. Fibrin glue-compounded MSCs were transplanted into the lesion of ANFH model, and the therapeutic efficacy was compared with uncompounded MSCs. One-Way ANOVA was used to determine the statistical significance among treatment groups. Results Fibrin glue compounding will not affect molecular activities of MSCs, including hepatocyte growth factor (HGF) secretion, cell proliferation and viability, and osteogenic differentiation in vitro. When applying fibrin glue-compounded MSCs for the therapy of ANFH in vivo, fibrin glue functioned as a drug delivery system and provided a sustaining microenvironment for MSCs which helped the relatively long-term secretion of HGF in the femoral head lesion and resulted in improved therapeutic efficacy when compared with uncompounded MSCs as indicated by hematoxylin-eosin staining and immunohistochemistry of osteocalcin, CD105 and HGF. Conclusion Transplantation of fibrin glue-compounding MSCs is a promising novel method for ANFH therapy. PMID:24885252
Histopathological effects of fibrin glue on penile fracture in a rat model.
Tasdemir, Cemal; Samdanci, Emine T; Turtay, Muhammet G; Firat, Cemal; Oguzturk, Hakan; Ozdemir, Hulya
2011-12-01
To evaluate both histopathological effects and potential clinical application of fibrin glue on the penile cavernosal tissue. Experimental penile fracture was formed by incising from the proximal dorsal side of the penis in 32 Wistar Albino rats. The rats were randomly assigned to four main groups of eight animals each. In the control group, the incision was not repaired and it was left to secondary healing. In the primary repair group, the incision was primarily repaired. In the fibrin glue group, glue was applied only to the incision. In the final group, fibrin glue was applied to the incision following primary repair. Three weeks later, penectomy tissue was examined histopathologically. When the control group was compared with primary repair+fibrin glue group, the differences in cavernous tissue healing with fibrosis and inflammation were statistically significant (p = 0.04 and 0.01, respectively). The primary repair+fibrin glue group, showed the best cavernous healing with fibrosis observed in only one rat. . There was no significant difference between the control group and the other groups according to cavernous tissue healing with fibrosis and inflammation (p = 0.11 and 0.12). Hyperemia was observed in the all groups of rats. Fibrin glue can be used in cavernoseal surgeries due to its adhesive and potentially anti-inflammatory features.
Fibrin glue as agent for sealing corneal and conjunctival wound leaks.
Scalcione, C; Ortiz-Vaquerizas, D; Said, D G; Dua, H S
2018-02-01
PurposeTo describe a novel use of fibrin glue in managing leaking blebs and leaking wounds following trauma or surgery.MethodsInterventional case series.ResultsWe report eight patients, including three where intra-operative or immediate post-penetrating keratoplasty recalcitrant leaks from the graft-host junction and/or openings created by the needle pass, were noted. All three had thin recipient beds in the sector of leak. This was managed by intra-cameral injection of fibrin glue in the affected quadrant. This stopped the leak and allowed the defect to heal. One patient of Descemets-stripping-endothelial-keratoplasty had leak from the surgical wound, which was also sealed with fibrin glue. Two patients with leaking glaucoma-surgery-related blebs were treated with intra-bleb injection of fibrin glue to stop the leak. One patient with a penetrating corneal injury with a metal wire had a brisk leak upon removal of the wire. This was sealed with fibrin glue. Another patient of chemical burn with spontaneous leaks was managed by glue injection in the perforations. Transient rise of intraocular pressure in one patient with a leaking bleb was the only adverse event recorded.ConclusionThis novel adaptation of the application of fibrin glue can help to deal with persistent intra-operative, post-operative and traumatic aqueous and air leaks.
Vivostat®: an autologous fibrin sealant as useful adjunct in endoscopic transnasal CSF-leak repair.
Tomazic, Peter Valentin; Edlinger, Stefan; Gellner, Verena; Koele, Wolfgang; Gerstenberger, Claus; Braun, Hannes; Mokry, Michael; Stammberger, Heinz
2015-06-01
The benefit of fibrin glue for reduction of postoperative CSF-leaks after endoscopic skull base surgery is not clearly evident in literature. However, its use is supposed to be beneficial in fixing grafting material. As of today there is no specific data available for otolaryngological procedures. A retrospective data analysis at a tertiary care referral center on 73 patients treated endoscopically transnasally for CSF-leaks at the ENT-department Graz between 2009 and 2012 was performed. Primary closure rate between conventional fibrin glue and autologous fibrin glue were analyzed. The Vivostat(®) system was used in 33 CSF-leak closures and in 40 cases conventional fibrin glue was used. Comparing the two methods the primary closure rate using the autologous Vivostat(®) system was 75.8 and 85.0 % with conventional fibrin glue. The secondary closure the rates were 90.9 % with Vivostat(®) 92.5 % with conventional fibrin glue. The Vivosat(®) system is a useful adjunct in endoscopic CSF-leak closure. Its advantages over conventional fibrin glue are its application system for fixation of grafting material particularly in underlay techniques. Despite this advantage it cannot replace grafting material or is a substitute for proper endoscopic closure which is reflected by the closure rates.
Cha, Dong Min; Kim, Kyeong Hwan; Choi, Hyuk Jin; Wee, Won Ryang
2012-01-01
Purpose To compare the effect of using fibrin glue or 10-0 nylon sutures on the clinical outcome of patients undergoing pterygium excision and conjunctival autografting. Methods We retrospectively reviewed the medical records of 52 eyes from 46 patients who underwent pterygium excision and conjunctival autografting and were followed up for more than 3 months. The operation duration, postoperative inflammation, complications, and recurrence rates were compared between groups of 20 patients (22 eyes) for whom fibrin glue was used (fibrin glue group) and 26 patients (30 eyes) for whom suturing was performed with 10-0 nylon (suture group) in pterygium excision and conjunctival autografting. Results The operation duration was 27.71 (5.22) minutes in the fibrin glue group and 43.30 (8.18) minutes in the suture group (p = 0.000). Seven days after the operation, the fibrin glue group showed milder conjunctival inflammation than the suture group (p = 0.000). Postoperative complications and corneal recurrence rates were not statistically different between the two groups. Conclusions The use of fibrin glue in pterygium excision with conjunctival autografting is likely to be a more effective, safer procedure than suturing. PMID:23204794
Fibrin glue versus autologous blood for conjunctival autograft fixation in pterygium surgery.
Boucher, Sophie; Conlon, Ronan; Teja, Salina; Teichman, Joshua C; Yeung, Season; Ziai, Setareh; Baig, Kashif
2015-08-01
To compare the outcomes between autologous blood- and fibrin glue-fixated conjunctival autografts in pterygium excision surgery. Retrospective case series. Forty eyes of 40 patients who had a primary nasal pterygium excision. A retrospective comparative case series of 40 eyes (40 patients) that had a primary nasal pterygium excision. All eyes had a conjunctival autograft from the superior bulbar conjunctiva to cover the scleral bed. Twenty eyes (20 patients) had fixation of the autograft using autologous blood (AB), and 20 eyes (20 patients) had fixation using fibrin glue (FG). One year of follow-up data included conjunctival graft stability (graft loss, graft retraction), pterygium recurrence, visual acuity, and postoperative complications. Descriptive and inferential statistics were performed. Intraoperatively, no complications occurred in either group. Graft loss occurred in 6 patients in the AB group, compared with none in the FG group. Graft retraction occurred in 3 patients in the AB group and 2 patients in the FG group. At 1 year postoperatively, pterygium recurrence occurred in 4 patients in the AB group and 1 patient in the FG group. One patient in the AB group developed a small pyogenic granuloma that resolved by 6 months with conservative management. Visual acuity remained stable in both groups. Conjunctival autograft fixation with autologous blood resulted in less stable conjunctival autografts and a higher recurrence rate compared with fixation with fibrin glue. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.
Fibrin glue as a protective tool for microanastomoses in limb reconstructive surgery.
Langer, Stefan; Schildhauer, Thomas A; Dudda, Marcel; Sauber, Jeannine; Spindler, Nick
2015-01-01
Fibrin glue becomes a more and more routinely used tool for stabilization of microanastomoses and nerve repair. This paper summarizes the technical properties and advantages of its use in a wide variety of microsurgical contexts, and includes an exemplary limb reconstructive case. A total of 131 patients who had undergone elective and emergency microsurgery mainly of the limbs were retrospectively analyzed, as was the use of free flaps. The use of fibrin glue allows for proper positioning of anastomoses and repaired nerves. No torsion of the pedicle could be seen. The flap survival rated >94%. The fibrin glue could stay in place in >99%. In the rare case of revision, the fibrin glue could easily be removed without damaging the region of the microanastomosis. Fibrin glue should not be used to repair insufficient, i.e., leaking anastomoses, but it does protect the site of anastomosis from tissue and fluid pressure. It prevents the pedickle from torsion and its use facilitates relocation of the microanastomoses in cases of revision surgery.
Fibrin glue as a protective tool for microanastomoses in limb reconstructive surgery
Langer, Stefan; Schildhauer, Thomas A.; Dudda, Marcel; Sauber, Jeannine; Spindler, Nick
2015-01-01
Aim: Fibrin glue becomes a more and more routinely used tool for stabilization of microanastomoses and nerve repair. This paper summarizes the technical properties and advantages of its use in a wide variety of microsurgical contexts, and includes an exemplary limb reconstructive case. Patients and methods: A total of 131 patients who had undergone elective and emergency microsurgery mainly of the limbs were retrospectively analyzed, as was the use of free flaps. Results: The use of fibrin glue allows for proper positioning of anastomoses and repaired nerves. No torsion of the pedicle could be seen. The flap survival rated >94%. The fibrin glue could stay in place in >99%. In the rare case of revision, the fibrin glue could easily be removed without damaging the region of the microanastomosis. Conclusion: Fibrin glue should not be used to repair insufficient, i.e., leaking anastomoses, but it does protect the site of anastomosis from tissue and fluid pressure. It prevents the pedickle from torsion and its use facilitates relocation of the microanastomoses in cases of revision surgery. PMID:26759762
Axillary lymphadenectomy for breast cancer in elderly patients and fibrin glue
2013-01-01
Background Axillary lymphadenectomy or sentinel biopsy is integral part of breast cancer treatment, yet seroma formation occurs in 15-85% of cases. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies with controversial results. Methods Thirty patients over 60 years underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray were applied to the axillary fossa in 15 patients; the other 15 patients were treated with harmonic scalpel. Results Suction drainage was removed between post-operative Days 3 and 4. Seroma magnitude and duration were not significant in patients receiving fibrin glue compared with the harmonic scalpel group. Conclusions Use of fibrin glue does not always prevent seroma formation, but can reduce seroma magnitude, duration and necessary evacuative punctures. PMID:24266959
Minimizing Collateral Brain Injury Using a Protective Layer of Fibrin Glue: Technical Note.
Basma, Jaafar; Latini, Francesco; Ryttlefors, Mats; Abuelem, Tarek; Krisht, Ali Fadl
2015-12-01
Neurosurgical procedures expose the brain surface to a constant risk of collateral injury. We describe a technique where the brain surface is covered with a protective layer of fibrin glue and discuss its advantages. A thin layer of fibrin glue was applied on the brain surface after its exposure in 34 patients who underwent different craniotomies for tumoral and vascular lesions. Data of 35 more patients who underwent standard microsurgical technique were collected as a control group. Cortical and pial injuries were evaluated using an intraoperative visual scale. Eventual abnormal signals at the early postoperative T2-weighted fluid-attenuated inversion recovery (T2FLAIR) magnetic resonance imaging (MRI) sequences were evaluated in oncological patients. Total pial injury was noted in 63% of cases where fibrin glue was not used. In cases where fibrin glue was applied, a significantly lower percentage of 26% (P < 0.01) had pial injuries. Only 9% had injuries in areas covered with fibrin glue (P < 0.0001). Early postoperative T2FLAIR MRI confirmed the differences of altered signal around the surgical field in the two populations. We propose beside an appropriate and careful microsurgical technique the possible use of fibrin glue as alternative, safe, and helpful protection during complex microsurgical dissections. Its intrinsic features allow the neurosurgeon to minimize the cortical manipulation preventing minor collateral brain injury. Copyright © 2015 Elsevier Inc. All rights reserved.
Fibrin glue for pilonidal sinus disease.
Lund, Jon; Tou, Samson; Doleman, Brett; Williams, John P
2017-01-13
Pilonidal sinus disease is a common condition that mainly affects young adults. This condition can cause significant pain and impairment of normal activities. No consensus currently exists on the optimum treatment for pilonidal sinus and current therapies have various advantages and disadvantages. Fibrin glue has emerged as a potential treatment as both monotherapy and an adjunct to surgery. To assess the effects of fibrin glue alone or in combination with surgery compared with surgery alone in the treatment of pilonidal sinus disease. In December 2016 we searched: the Cochrane Wounds Specialised Register; CENTRAL; MEDLINE; Embase and CINAHL Plus. We also searched clinical trials registries and conference proceedings for ongoing and unpublished studies and scanned reference lists to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We included randomised controlled trials (RCTs) only. We included studies involving participants of all ages and studies conducted in any setting. We considered studies involving people with both new and recurrent pilonidal sinus. We included studies which evaluated fibrin glue monotherapy or as an adjunct to surgery. Two study authors independently extracted data and assessed risk of bias. We used standard methods expected by Cochrane. We included four RCTs with 253 participants, all were at risk of bias. One unpublished study evaluated fibrin glue monotherapy compared with Bascom's procedure, two studies evaluated fibrin glue as an adjunct to Limberg flap and one study evaluated fibrin glue as an adjunct to Karydakis flap.For fibrin glue monotherapy compared with Bascom's procedure, there were no data available for the primary outcomes of time to healing and adverse events. There was low-quality evidence of less pain on day one after the procedure with fibrin glue monotherapy compared with Bascom's procedure (mean difference (MD) -2.50, 95% confidence interval (CI) -4.03 to -0.97) (evidence downgraded twice for risk of performance and detection bias). Fibrin glue may reduce the time taken to return to normal activities compared with Bascom's procedure (mean time 42 days with surgery and 7 days with glue, MD -34.80 days, 95% CI -66.82 days to -2.78 days) (very low-quality evidence, downgraded as above and for imprecision).Fibrin glue as an adjunct to the Limberg flap may reduce the healing time from 22 to 8 days compared with the Limberg flap alone (MD -13.95 days, 95% CI -16.76 days to -11.14 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). It is uncertain whether use of fibrin glue affects the incidence of postoperative seroma (an adverse event) (risk ratio (RR) 0.27, 95% CI 0.05 to 1.61; very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). There was low-quality evidence that fibrin glue, as an adjunct to Limberg flap, may reduce postoperative pain (median 2 versus 4; P < 0.001) and time to return to normal activities (median 8 days versus 17 days; P < 0.001). The addition of fibrin glue to the Limberg flap may reduce the length of hospital stay (MD -1.69 days, 95% CI -2.08 days to -1.29 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for unexplained heterogeneity).A single RCT evaluating fibrin glue as an adjunct to the Karydakis flap did not report data for the primary outcome of time to healing. It is uncertain whether fibrin glue with the Karydakis flap affects the incidence of postoperative seroma (adverse event) (RR 3.00, 95% CI 0.67 to 13.46) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for imprecision). Fibrin glue as an adjunct to Karydakis flap may reduce length of stay but this is highly uncertain (mean 2 days versus 3.7 days; P < 0.001, low-quality evidence downgraded twice for risk of selection, performance and detection bias). Current evidence is uncertain regarding any benefits associated with fibrin glue either as monotherapy or as an adjunct to surgery for people with pilonidal sinus disease. We identified only four RCTs and each was small and at risk of bias resulting in very low-quality evidence for the primary outcomes of time to healing and adverse events. Future studies should enrol many more participants, ensure adequate randomisation and blinding, whilst measuring clinically relevant outcomes.
Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.
Schmandra, T C; Bauer, H; Petrowsky, H; Herrmann, G; Encke, A; Hanisch, E
2001-07-01
Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated. Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals. Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities. Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.
Yang, Kai-Chiang; Wang, Chun-Hao; Chang, Hao-Hueng; Chan, Wing P; Chi, Chau-Hwa; Kuo, Tzong-Fu
2012-11-01
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.
Wu, Xiuwen; Ren, Jianan; Wang, Gefei; Wang, Jianzhong; Wang, Feng; Fan, Yueping; Li, Yuanxin; Han, Gang; Zhou, Yanbing; Song, Xiaofei; Quan, Bin; Yao, Min; Li, Jieshou
2015-10-07
The management of an enterocutaneous fistula poses a significant challenge to surgeons and is often associated with a costly hospital stay and long-term discomfort. The use of fibrin glue in the fistula tract has been shown to promote closure of low output enterocutaneous fistulas. Our previous nonrandomized study demonstrated that autologous platelet-rich fibrin glue treatment significantly decreased time to fistula closure and promoted closure rates. However, there are several limitations in the study, which may lead to bias in our conclusion. Thus, a multicenter, randomized, controlled clinical trial is required. The study is designed as a randomized, open-label, three-arm, multicenter study in nine Chinese academic hospitals for evaluating the efficacy and safety of fibrin glue for sealing low-output fistulas. An established number of 171 fistula patients will undergo prospective random assignment to autologous fibrin glue, commercial porcine fibrin sealants or drainage cessation (1:1:1). The primary endpoint is fistula closure time (defined as the interval between the day of enrollment and day of fistula closure) during the 14-day treatment period. To our knowledge, this is the first study to evaluate the safety and efficacy of both autologous and commercial fibrin glue sealing for patients with low-output volume fistulas. NCT01828892 . Registration date: April 2013.
Efficacy of bubaline fibrin glue on full-thickness pinch and punch skin grafting in a pig.
Dejyong, Krittee; Kaewamatawong, Theerayuth; Brikshavana, Pasakorn; Durongphongtorn, Sumit
2017-03-01
Fibrin glue, which is formed from the action of thrombin (a serine protease) on fibrinogen, has been developed for use as an adhesive to increase the success of skin graft surgery. The objective of this study was to evaluate if bubaline fibrin glue would promote skin graft survival in pigs. The grafting was divided into two steps. First, granulation wound preparation was performed in a healthy swine by creating four full-skin depth wounds (3 × 12 cm 2 ) at the dorsal part of the loin area on each side. Second, pinch and punch skin grafting, where eight skin discs (0.6 cm diameter) were regularly placed (0.6 cm distance apart) in the granulation tissue bed of each wound, was performed 5 days later. The bubaline fibrin glue was added prior to application of the 16 skin graft discs in two of the wounds, while no glue was added to the other 16 skin graft discs in the other two wounds. The number of surviving graft pieces and histological examination was evaluated after 3, 7, and 14 days post-operation and compared by pairing between the control and the bubaline fibrin glue groups. The number of grafts that remained at 3 and 7 days post-operation and the number of new microvessels at 3 days post-operation were significantly higher ( p < 0.05) in the bubaline fibrin glue group than in the control group. However, there was no significant difference in the number of fibroblasts, the intensity of scarring and the intensity of inflammation between the two groups, except for the significantly lower intensity of inflammation at 7 days post-operation in the bubaline fibrin glue group. In conclusion, bubaline fibrin glue has the advantage of decreasing the skin graft loss by approximately 31.3-37.5% compared with the control group and also promotes angiogenesis.
Fibrin glue as a hemostatic agent in hepatic and splenic trauma.
Ochsner, M G; Maniscalco-Theberge, M E; Champion, H R
1990-07-01
Fibrin glue is a biologic hemostatic agent that coagulates and seals upon application. It is made by combining human fibrinogen concentrate with standard thrombin solutions containing calcium. Similar to epoxy glue, the two components are applied simultaneously in equal volumes resulting in an almost instantaneous formation of a coagulum. Fibrinogen concentrate is prepared in the blood bank from single donor plasma. Fibrin glue can be applied topically or injected into the parenchyma of solid organs. Twenty-six patients sustained hepatic or splenic trauma from May through August 1989--17 liver and nine splenic injuries. The glue was effective after one application in 21 patients and after a second in five. Hemostasis was achieved despite coagulopathy and thrombocytopenia in eight patients. There were no re-explorations for bleeding, and nine complications occurred in six patients. Our experience suggests fibrin glue is an effective, underutilized adjunctive hemostatic agent in trauma.
Clinical experience with fibrin glue in cardiac surgery.
Köveker, G; de Vivie, E R; Hellberg, K D
1981-10-01
Cardiac surgery is often associated with hemostatic abnormalities leading to severe bleeding. Special problems are to be expected, if prosthetic material has to be implanted. Preclotting of Dacron prostheses with blood is well established but failures are sometimes encountered. Several years ago a new hemostatic sealing system (fibrin glue) was introduced into therapy. Since 1978 fibrin glue has been applied in 176 patients. The indications were: 1. sealing of woven Dacron prostheses, 2. bleeding from suture-holes (Gore-Tex), 3. diffuse myocardial bleeding and 4. prevention of kinking of coronary artery grafts. In 32 patients with an aortoventriculoplasty operation using Dacron the "blood preclotting" and "fibrin sealing" methods were compared. In the fibrin glue group there was a significant reduction in postoperative blood loss as well as a shortening of the operation time (period of protamin administration to skin closure). No fibrinolytic dissolution of the fibrin layer on the prostheses was observed.
Effectiveness of Fibrin Glue in Adherence of Skin Graft.
Reddy, Konda Sireesha; Chittoria, Ravi Kumar; Babu, Preethitha; Marimuthu, Senthil Kumaran; Kumar, Sudhanva Hemanth; Subbarayan, Elan Kumar; Chavan, Vinayak; Mohapatra, Devi Prasad; Sivakumar, Dinesh Kumar; Friji, M T
2017-01-01
Graft fixation is important for graft take. Fibrin glue has been proposed as an ideal material, because of its human origin and it provides firm adhesion in seconds or minutes. To evaluate the efficiency of fibrin glue, in increasing the take of skin graft. Assessment includes surgical time taken for graft fixation, haematoma/seroma formation, engraftment and wound closure by day 14. The study is an observational prospective study conducted in the Department of Plastic Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, from January 2016 to June 2016. Sixteen patients who underwent split skin grafting were assessed during the study period. Fibrin glue was used on the recipient bed before grafting. Better haemostasis and graft adhesion, with a significant reduction of surgical time, were noted. The safety profile of fibrin glue was excellent as indicated by the lack of any related serious adverse experiences. These findings demonstrate that it is safe and effective for attachment of skin grafts, with outcomes at least as good as conventional methods.
Mishiro, Tsuyoshi; Shibagaki, Kotaro; Matsuda, Kayo; Fukuyama, Chika; Okada, Mayumi; Mikami, Hironobu; Izumi, Daisuke; Yamashita, Noritsugu; Okimoto, Eiko; Fukuda, Naoki; Aimi, Masahito; Fukuba, Nobuhiko; Oshima, Naoki; Takanashi, Toshihiro; Matsubara, Takeshi; Ishimura, Norihisa; Ishihara, Shunji; Kinoshita, Yoshikazu
2016-08-01
In recent years, treatment techniques in which polyglycolic acid sheets are applied to various situations with fibrin glue have exhibited great clinical potential, and previous studies have reported safety and efficacy. We describe closure of a non-healing perforated duodenal ulcer with the use of a polyglycolic acid sheet and fibrin glue in an elderly patient who was not a candidate for surgery.
Effect of collagen sponge and fibrin glue on bone repair
SANTOS, Thiago de Santana; ABUNA, Rodrigo Paolo Flores; de ALMEIDA, Adriana Luisa Gonçalves; BELOTI, Marcio Mateus; ROSA, Adalberto Luiz
2015-01-01
ABSTRACT The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. Material and Methods Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p≤0.05). Results Three-dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. Conclusion Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous. PMID:26814464
Adhesive arachnoiditis after percutaneous fibrin glue treatment of a sacral meningeal cyst.
Hayashi, Kazunori; Nagano, Junji; Hattori, Satoshi
2014-06-01
The authors present the case of a 64-year-old woman who was referred for severe sacral pain. She reported that her pain had been longstanding, and had greatly increased after percutaneous fibrin glue placement therapy for a sacral meningeal cyst 2 months earlier at a different hospital. An MRI scan obtained immediately after fibrin glue placement at that hospital suggested that fibrin glue had migrated superiorly into the subarachnoid space from the sacral cyst to the level of L-4. On admission to the authors' institution, physical examination demonstrated no abnormal findings except for perianal hypesthesia. An MRI study obtained at admission demonstrated a cystic lesion in the peridural space from the level of S-2 to S-4. Inhomogeneous intensity was identified in this region on T2-weighted images. Because the cauda equina and nerve roots appeared to be compressed by the lesion, total cyst excision was performed. The cyst cavity was filled with fluid that resembled CSF, plus gelatinous material. Histopathological examination revealed that the cyst wall was composed of hyaline connective tissue with some calcification. No nervous tissue or ganglion cells were found in the tissue. The gelatinous material was acellular, and appeared to be degenerated fibrin glue. Sacral pain persisted to some extent after surgery. The authors presumed that migrated fibrin glue caused the development of adhesive arachnoiditis. The risk of adhesive arachnoiditis should be considered when this therapy is planned. Communication between a cyst and the subarachnoid space should be confirmed to be sufficiently narrow to prevent the migration of injected fibrin glue.
Amplitude of Glottal Mucosal Wave After Vocal Fold Microflap With or Without Fibrin Glue.
González-Herranz, Ramón; Amarillo, Elizabeth; Hernández-García, Estefanía; Montojo Woodeson, José; Plaza-Mayor, Guillermo
2017-05-01
The vocal fold microflap technique is the ideal to remove benign vocal fold pathology. Our objective is to compare the amplitudes of the mucosal wave before and after the closure of microflap defect with fibrin glue, and when microflap is left to heal by secondary intention. The present study is a retrospective series, including 32 patients treated by intracordal phonosurgery, with closure of the microflap either with fibrin glue or by healing by secondary intention. They all had both preoperative and 6-month postoperative track records to allow voice analysis, a subjective Voice Handicap Index 10 (VHI-10), and a good image quality strobe. After selecting the patients was found that the mean overall preoperative VHI-10 was 26.6, and improved up to 10.5 after surgery, a statistical differences (P = 0.03). When comparing both groups, with or without fibrin glue, fibrin glue did not improved results in VHI-10. On the contrary, there was a significant difference in the improvement of the open glottal phase after surgery (P = 0.03), showing a much higher improvement when fibrin glue was used. The use of fibrin glue after a vocal fold microflap for advanced pathology, such as sulcus vocalis in pocket, vergeture, or vocal fold scar, increases the amplitude of the mucosal wave of the vocal folds, but does not improve the VHI-10 results in our cohort of female patients. So far, patient-reported outcome shows that healing by secondary intention continues to provide excellent voice results. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Melendez, Mark M; Martinez, Rodrigo R; Dagum, Alexander B; McClain, Steve A; Simon, Marcia; Sobanko, Joseph; Zimmerman, Thomas; Wetterau, Meredith; Muller, Douglas; Xu, Xiaoti; Singer, Adam J; Arora, Balvantray
2008-01-01
BACKGROUND: An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing. OBJECTIVE: To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes. METHODS: Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension. RESULTS: Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra. CONCLUSIONS: It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension. PMID:19721792
Conaglen, Paul J; Collier, Neil A
2014-04-01
Various techniques have been described to try and reduce the rate of anastomotic leak following pancreaticoduodenectomy, which remains a challenge for pancreatic surgeons worldwide. We outline a technique to reinforce the pancreatic anastomosis with a double layer of fibrin glue between suture lines. Our technique for pancreatic anastomosis is described in detail. A review of consecutive pancreaticoduodenectomies by a single surgeon (NAC) since introduction of fibrin glue anastomosis reinforcement was compared with a historical control cohort performed by the same surgeon. Thirty-two consecutive pancreaticoduodenectomies were undertaken between March 2008 and March 2012 by a single surgeon, 30 patients had fibrin glue augmentation of the pancreatico-gastrostomy anastomosis. Median length of stay was 12 days. There were no pancreatic leaks or mortality since adopting fibrin glue for the pancreatic anastomosis; however; this single surgeon series is not large enough to provide statistical evidence of a difference since glue was adopted. Our results since the incorporation of this step in pancreaticoduodenectomy are encouraging. Selective use of glue is worthy of consideration in difficult cases, although confirmation of a reduction in pancreatic leak rate is not yet established, and we advocate a multi-institution randomized controlled trial to explore this. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.
Autologous Blood Versus Fibrin Glue in Pterygium Excision With Conjunctival Autograft Surgery.
Nadarajah, Gaayathri; Ratnalingam, Vanitha Hema; Mohd Isa, Hazlita
2017-04-01
To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery. A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment. All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238). Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.
Oshino, Satoru; Saitoh, Youichi; Yoshimine, Toshiki
2010-06-01
To examine the strength and tolerance of the fibrin glue sealant in a situation of extended transsphenoidal surgery. The withstand pressure of fibrin glue sealant was measured using a simple sellar reconstruction model. A 15-mm diameter hole at the bottom of a 51-cm high cylinder was covered with a Gore-Tex (Gore-Tex, Tokyo, Japan) sheet. A small plate was placed on the center for a brief fixation, and 3 mL of fibrin glue was applied over the entire bottom. Then water was gradually filled in five cylinders, and the water level at leakage was measured as withstand pressures at 10 minutes and 24 hours after sealant application. The stability of the sealant under pressures of 20 and 30 cm H(2)O for 12 hours was also examined. The median initial withstand pressure at 10 minutes was 32 cm H(2)O (n = 5), and was significantly increased to 47.5 cm H(2)O after 24 hours (n = 4). In four of five cylinders, fibrin glue sealants were stable against a pressure of 20 cm H(2)O for 12 hours and 30 cm H(2)O for the next 12 hours. The withstand pressure of simple fibrin glue sealant without other biological reactions could be estimated to be more than 20 cm H(2)O after application, and increased to more than 40 cm H(2)O after 24 hours. These data are practical for neurosurgeons to comprehend the strength and limit of fibrin glue sealant and suggests the importance to control the intracranial pressure to less than 20 cm H(2)O, especially for the first 12 to 24 hours. Copyright © 2010 Elsevier Inc. All rights reserved.
Küçükerdönmez, Cem; Karalezli, Aylin; Zengin, Mehmet Ozgur; Akova, Yonca Aydin
2014-01-01
To monitor the development of graft vascularization after pterygium excision with conjunctival autograft transplantation (CAT) using indocyanine green angiography (ICGA) and to compare the graft vascularization between 2 different fixation techniques (fibrin glue and sutures). A total of 26 eyes of 26 patients with primary pterygium were randomly assigned after pterygium excision as having either fibrin glue (13 eyes) or Vicryl sutures (13 eyes) for CAT. Anterior segment ICGA findings were evaluated postoperatively at 1, 7, and 15 days and the percentages of graft vascularization in both groups were compared using pixel analysis software program. The mean ± SD age of patients in the suture and fibrin glue groups was 52.1 ± 12.7 years and 57.1 ± 9.82 years, respectively. There was no statistically significant difference between the groups regarding age, sex, or follow-up (p<0.05 for all). Also, the mean intraoperative defect size was not significantly different between the groups, which was measured as 20.11 ± 10.44 mm2 in the suture group and 23.44 ± 12.34 mm2 in the fibrin glue group (p = 0.343). The mean percentage of vascularized graft area at postoperative day 1 and 7 was 18.1 ± 7.8% and 25.3 ± 8.6% in the suture group and 34.8 ± 10.2% and 66.1 ± 17.8% in the fibrin glue group. The difference between the groups was statistically significant (p<0.01 for both). At postoperative day 15, all grafts were 100% perfused in both groups. Fibrin glue fixation of conjunctival autografts led to more vascularization in the early postoperative period than suture fixated grafts, which in turn may have significance in terms of graft health and pterygium recurrence.
Sugawara, Taku; Itoh, Yasunobu; Hirano, Yoshitaka; Higashiyama, Naoki; Shimada, Yoichi; Kinouchi, Hiroyuki; Mizoi, Kazuo
2005-10-01
Extradural or subcutaneous cerebrospinal fluid (CSF) leakage is a common complication after spinal surgery and is associated with the risks of poor wound healing, meningitis, and pseudomeningocele. Numerous methods to prevent postoperative CSF leakage are available, but pressure-tight dural closure remains difficult, especially with synthetic surgical membranes. The efficacy of a novel dural closure technique was assessed by detecting extradural or subcutaneous CSF leakage on magnetic resonance imaging. The novel dural closure technique using absorbable polyglactin acid sheet and fibrin glue and the conventional procedure using only fibrin glue were evaluated retrospectively by identifying extradural or subcutaneous CSF leakage on magnetic resonance imaging scans in the acute (2-7 d) and chronic (3-6 mo) postoperative stages after spinal intradural surgery in 53 patients. The incidence of extradural and subcutaneous CSF leakage was significantly lower (P < 0.05) in the acute (20%) and chronic (0%) stages using polyglactin acid sheet and fibrin glue in 15 patients compared with that in the acute (81%) and chronic (24%) stages using only fibrin glue in 38 patients. One patient in the fibrin glue-only group required repair surgery for cutaneous CSF leakage. The combination of polyglactin acid sheet and fibrin glue can achieve water-tight closure after spinal intradural surgery and can minimize the risk of intractable postoperative CSF leakage. This simple, economical technique is recommended for dural closure after spinal intradural surgery.
Dura covered with fibrin glue reduces adhesions in abdominal wall defects.
Schier, F; Srour, N; Waldschmidt, J
1991-12-01
Dura can greatly facilitate the closure of abdominal wall defects. However, a main disadvantage of its use are the adhesions which develop between omentum, bowel and dura and may lead to bowel obstructions. In this study various groups of rats had either the anterior wall replaced by untreated dura or by dura covered with fibrin glue prior to implantation. Adhesions were found in 75% of sham operated rats, 100% after untreated dura implantation and 50% after the implantation of fibrin glue treated dura.
Chen, Wei-liang; Huang, Zhi-quan; Zhang, Da-ming; Chai, Qiang
2010-04-01
Surgical excision is useful only for localized and limited lesions. The purpose of this study was to evaluate the clinical curative effect of percutaneous sclerotherapy of massive venous malformations of the face and neck using fibrin glue combined with OK-432 and pingyangmycin. Eighteen patients with massive venous malformations were treated with an injection of fibrin glue combined with OK-432 and pingyangmycin. All the patients had extreme swelling postoperatively with no major complications. The follow-up period ranged from 6 to 12 months. Twelve lesions were completely involuted, 4 lesions were mostly involuted, and 2 lesions were partially involuted. All of the patients had normal liver and kidney functions. None of the patients presented with hematologic toxic effects or signs of pulmonary involvement. Percutaneous sclerotherapy using fibrin glue combined with OK-432 and pingyangmycin provided a simple, safe, and reliable alternative treatment for massive venous malformations.
Restoration of small bone defects at craniotomy using autologous bone dust and fibrin glue.
Matsumoto, K; Kohmura, E; Kato, A; Hayakawa, T
1998-10-01
Bone gaps or burr holes often result in small but undesirable scalp or skin depressions after craniotomy. Whereas a number of reports have discussed cranioplasties to avoid large bone defects, little has been written about the problem of small bone defects which, despite their minor size, could result in bothersome cosmetic problems. This study was designed to assess a simple method to repair burr hole defects and bridge bone gaps with autologous bone dust and fibrin glue. Bone dust was collected when burr holes were created or craniectomy was performed. After replacement of the bone flap, the burr holes or bone gap were filled with a mixture of bone dust and fibrin glue. The mixture of bone dust and fibrin glue was easily shaped to fit bone defects, resulting in favorable cosmetic outcomes 1 to 5 years after operation.
Closure of ascites leaks with fibrin glue injection in patients with end-stage liver disease.
Sadik, Karim W; Laibstain, Sarah; Northup, Patrick G; Kashmer, David; Schmitt, Timothy M; Bonatti, Hugo J R
2011-09-01
Ascites leaks (AL) in patients with end-stage liver disease (ESLD) are associated with significant morbidity and mortality regardless if they are medically or surgically managed. In a pilot study, 14 ESLD patients with AL underwent treatment with fibrin glue injection around the leak after failing conservative therapy. The end point of this study was the cessation of AL in the short term and the maintenance of a leak-free abdomen in the long term, allowing for medical optimization of the patients. Median age of the 10 men and 4 women was 50 (range 26-67) years. Underlying ESLDs were chronic hepatitis C (n=5), alcoholic LD (n=2), cryptogenic cirrhosis (n=2), and miscellaneous (n=5). There were six leaking incisions posthernia repair (three umbilical and three inguinal), two leaking/ruptured umbilical hernias, four leaking paracentesis sites, one leaking Jackson-Pratt (JP) drain canal, and one leaking laparoscopic trocar site. Average AL volume per day was 1000 (range 400-2000) mL. All leaks were immediately resolved with a 3-5 mL fibrin glue injection. Five recurred and required a second injection (four within 24 hours). Mental status improved in 7 patients (West Haven Criteria: grade II to I [n=6], grade III to I [n=1]). Median model of end-stage liver disease scores improved from 23 (range 8-33) to 20 (range 14-26). There were no infections, bleeds, or other injection-related complications. Average follow-up for these patients was 441.6 days (range 2-852). Five patients underwent liver transplant (LT) median 15 (range 4-270) days postinjection; 2 of them died. Another 3 patients died (2 from sepsis and 1 from metastatic cancer). Fibrin glue injection for the control of AL is a simple and safe bedside procedure that quickly controls AL, allowing for patient recovery in anticipation of further care.
An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery
Khodakaram-Tafti, Azizollah; Mehrabani, Davood; Shaterzadeh-Yazdi, Hanieh
2017-01-01
The purpose of this review is to have an overview on the applications on the autologous fibrin glue as a bone graft substitute in maxillofacial injuries and defects. A search was conducted using the databases such as Medline or PubMed and Google Scholar for articles from 1985 to 2016. The criteria were “Autograft,” “Fibrin tissue adhesive,” “Tissue engineering,” “Maxillofacial injury,” and “Regenerative medicine.” Bone tissue engineering is a new promising approach for bone defect reconstruction. In this technique, cells are combined with three-dimensional scaffolds to provide a tissue-like structure to replace lost parts of the tissue. Fibrin as a natural scaffold, because of its biocompatibility and biodegradability, and the initial stability of the grafted stem cells is introduced as an excellent scaffold for tissue engineering. It promotes cell migration, proliferation, and matrix making through acceleration in angiogenesis. Growth factors in fibrin glue can stimulate and promote tissue repair. Autologous fibrin scaffolds are excellent candidates for tissue engineering so that they can be produced faster, cheaper, and in larger quantities. In addition, they are easy to use and the probability of viral or prion transmission may be decreased. Therefore, autologous fibrin glue appears to be promising scaffold in regenerative maxillofacial surgery. PMID:28584530
Fibrin glue versus sutures for conjunctival autografting in primary pterygium surgery.
Romano, Vito; Cruciani, Mario; Conti, Luigi; Fontana, Luigi
2016-12-02
Pterygium, a growth of the conjunctiva over the cornea, is a progressive disease leading in advanced stages to visual impairment, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence can be a problem. Currently the best surgical option in terms of recurrence is conjunctival autograft. To date the most common surgical methods of attaching conjunctival autografts to the sclera are through suturing or fibrin glue. Each method presents its own advantages and disadvantages. Sutures require considerable skill from the surgeon and can be associated with a prolonged operation time, postoperative discomfort and suture-related complications, whereas fibrin glue may give a decreased operation time, improve postoperative comfort and avoid suture-related problems. To assess the effectiveness of fibrin glue compared to sutures in conjunctival autografting for the surgical treatment of pterygium. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2016), Embase (January 1980 to October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 October 2016. We included randomised controlled trials (RCTs) in any setting where fibrin glue was compared with sutures to treat people with pterygium. Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcome was recurrence of pterygium defined as any re-growth of tissue from the area of excision across the limbus onto the cornea. The secondary outcomes were surgical time and complication rate. We graded the certainty of the evidence using GRADE. We included 14 RCTs conducted in Brazil, China, Egypt, India, Malaysia, New Zealand, Philippines, Saudi Arabia, Sweden and Turkey. The trials were published between 2004 and 2016, and were assessed as a mixture of unclear and low risk of bias with three studies at high risk of attrition bias. Only adults were enrolled in these studies.Using fibrin glue for the conjunctival autograft may result in less recurrence of pterygium compared with using sutures (risk ratio (RR) 0.47, 95% CI 0.27 to 0.82, 762 eyes, 12 RCTs; low-certainty evidence). If pterygium recurs after approximately 10 in every 100 surgeries with sutures, then using fibrin glue may result in approximately 5 fewer cases of recurrence in every 100 surgeries (95% CI 2 fewer to 7 fewer cases). Using fibrin glue may lead to more complications compared with sutures (RR 1.92; 95% CI 1.22 to 3.02, 11 RCTs, 673 eyes, low-certainty evidence). The most common complications reported were: graft dehiscence, graft retraction and granuloma. On average using fibrin glue may mean that surgery is quicker compared with suturing (mean difference (MD) -17.01 minutes 95% CI -20.56 to -13.46), 9 RCTs, 614 eyes, low-certainty evidence). The meta-analyses, conducted on people with pterygium in a hospital or outpatient setting, show fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. There was low-certainty evidence to suggest a higher proportion of complications in the fibrin glue group.
Panda, Anita; Kumar, Sandeep; Kumar, Abhiyan; Bansal, Raseena; Bhartiya, Shibal
2009-01-01
Suturing is a time consuming task in ophthalmology and suture induced irritation and redness are frequent problems. Postoperative wound infection and corneal graft rejection are examples of possible suture related complications. To prevent these complications, ophthalmic surgeons are switching to sutureless surgery. A number of recent developments have established tissue adhesives like cyanoacrylate glue and fibrin glue as attractive alternatives to sutures. A possible and promising new application for tissue adhesives is to provide a platform for tissue engineering. Currently, tissue glue is being used for conjunctival closure following pterygium and strabismus surgery, forniceal reconstruction surgery, amniotic membrane transplantation, lamellar corneal grafting, closure of corneal perforations and descematoceles, management of conjunctival wound leaks after trabeculectomy, lid surgery, adnexal surgery and as a hemostat to minimise bleeding. The purpose of this review is to discuss the currently available information on fibrin glue. PMID:19700876
Comparison of Fibrin Glue and Sutures for Conjunctival Wound Closure in Strabismus Surgery
Lee, Jae Hyung
2011-01-01
Purpose To evaluate and compare the efficacy and tolerance of fibrin glue and sutures for closing conjunctival wounds in strabismus surgery. Methods In a prospective trial, we performed strabismus surgery using limbal incisions. Conjunctival wounds were closed with fibrin glue in 20 eyes of 20 patients (fibrin group) and 8-0 polyglactin suture in 20 eyes of 20 patients (suture group). Postoperative pain, tearing, and inflammation were compared at 1 day, 1 week, 3 weeks, and 6 weeks after surgery. Conjunctival incision healing was also investigated. Results One day and one week post-operatively, pain and tearing scores were lower in the fibrin group (p = 0.000, respectively). Mean surgery time was significantly shorter in the fibrin (48 ± 5 minutes) than the suture group (63 ± 7 minutes) (p = 0.000). Inflammation was significantly more severe in the suture group until 3 weeks postoperative (p = 0.000, respectively), but conjunctival healing did not differ between the groups. Hyperemia appeared more prominent in the fibrin group 3 and 6 weeks after surgery (p = 0.087 and 0.000, respectively). Two eyes in the fibrin group showed conjunctival gaps of more than 2 mm, which closed spontaneously by three weeks after surgery. No allergic reactions or infections developed. Conclusions Fibrin glue proved to be as effective as sutures in closing conjunctival wounds. It provides more comfortable early postoperative courses and might be considered as an alternative to sutures in strabismus surgery. PMID:21655043
Brennan, M
1991-12-01
Fibrin glue is a topical biological adhesive, the effect of which imitates the final stages of coagulation. The glue consists of a solution of concentrated human fibrinogen which is activated by the addition of bovine thrombin and calcium chloride. The resultant clot aids haemostasis and tissue sealing and is completely absorbed during wound healing without foreign body reaction or extensive fibrosis. The fibrinogen component of fibrin glue can be produced from fresh frozen plasma obtained from single unit donations thereby reducing the risks of transfusion transmitted infections encountered by exposure to pools from large numbers of donors. Methods involving precipitation of fibrinogen by cryoprecipitation, polyethylene glycol or ammonium sulphate have been described and evaluated. The risk of transmission of infection can be further reduced by using plasma from 'accredited donors' who are plasma donors regularly tested for ALT and markers of viral infection or by use of fibrinogen prepared in advance of surgery from autologous blood. The second component, a mixture of thrombin and CaCl2, is quantitatively and qualitatively well defined and commercially available (Armour Pharmaceutical Co., Thrombinar (bovine thrombin]. Thrombin is applied to the operation site simultaneously and in equal volume to the fibrinogen but from a separate syringe. In the UK a commercial heat treated fibrin glue prepared from pooled plasma is available on a doctor/named patient basis (Tisseel, Immuno, Vienna). The haemostatic and adhesive properties of fibrin glue can be employed in virtually every surgical specialty. The usefulness of the glue is particularly well documented in the fields of cardiovascular surgery, ENT and neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Tschopp, J M; Evéquoz, D; Karrer, W; Aymon, E; Naef, A P
1990-03-01
We report a case of chronic debilitating BPF following right upper lobe resection. Despite several endobronchial applications of fibrin glue, we could not close it. Since the patient was extremely debilitated by symptoms due to the BPF, a thoracoplasty was attempted but was not successful. Finally, the BPF was definitely closed by instillation of talc into the pleura through thoracoscopy. To our knowledge, this is the first reported case of chemical closure of a recalcitrant BPF by the route of thoracoscopy. It also shows the failure of endoscopic fibrin glue application in such a condition.
Ladi, Jeevan S; Shah, Nitant A
2013-01-01
We report the first case of vertical fixation by fibrin glue-assisted secondary posterior chamber intraocular lens implantation in a case of surgical aphakia. Advantages of vertical fixation are discussed. PMID:23514650
Injectable tissue-engineered cartilage using commercially available fibrin glue.
Cakmak, Ozcan; Babakurban, Seda T; Akkuzu, Hatice G; Bilgi, Selcuk; Ovalı, Ercüment; Kongur, Merve; Altintas, Hande; Yilmaz, Bayram; Bilezikçi, Banu; Celik, Zerrin Y; Yakicier, Mustafa C; Sahin, Feride I
2013-12-01
To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration. Animal research. A total of 28 immunocompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis. The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference. We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Stoikes, Nathaniel; Webb, David; Powell, Ben; Voeller, Guy
2013-11-01
The Rives repair for ventral/incisional (V/I) hernias involves sublay mesh placement requiring retrorectus dissection and transfascial stitches. Chevrel described a repair by onlaying mesh after a unique primary fascial closure. Although Chevrel fixated mesh to the anterior fascia with sutures, he used fibrin glue for fascial closure reinforcement. We describe an onlay technique with mesh fixated to the anterior fascia solely with fibrin glue without suture fixation. From January 2010 to January 2012, 50 patients underwent a V/I hernia onlay technique with fibrin glue mesh fixation. Records were reviewed for technical details, demographics, mesh characteristics, and postoperative outcomes. Primary fascial closure with interrupted permanent suture was done with or without myofascial advancement flaps. Onlay polypropylene mesh was placed providing 8 cm of overlap. Fibrin glue was applied over the prosthesis and subcutaneous drains were placed. Mean age was 62.4 years. Mean body mass index was 30.1 kg/m(2). Average mesh size was 14.5 cm × 19.1 cm. Mean operative time was 144.4 minutes (range, 38 to 316 minutes). Mean discharge was postoperative Day 2.9 (range, 0 to 15 days). Morbidity included eight seromas, one hematoma, and three wound infections. Seventeen patients required components separation. Mean follow-up was 19.5 months with no recurrences. This is the first series describing fibrin glue alone for mesh fixation for V/I hernia repair. It allows for immediate prosthesis fixation to the anterior fascia. Early results are promising. Potential advantages include less operative time, less technical difficulty, and less long-term pain. A prospective trial is needed to evaluate this approach.
Sakai, Takashi; Matsutani, Noriyuki; Kanai, Eiichi; Yamauchi, Yoshikane; Uehara, Hirofumi; Iinuma, Hisae; Kawamura, Masafumi
2018-02-01
Polyglycolic acid and oxidized regenerated cellulose have been widely used as a sealant for repairing pulmonary air leakage during respiratory surgery. However, fundamental research of these materials has not been sufficiently conducted. Therefore, we conducted studies to assess the pressure resistance ability of these materials using a canine visceral pleural defect model at the early phase. The 6-mm circular defect and the 12-mm square defect were created on the visceral pleura of anesthetized beagles. These defects were then repaired using one of four methods: method A using polyglycolic acid and fibrin glue; method B using oxidized regenerated cellulose and fibrin glue; method C using oxidized regenerated cellulose; method D using fibrin glue. Airway pressure was measured as bursting pressure when air leakage from the repaired areas occurred at 5 min, 3 h, and 24 h after repair. For the 6-mm circle defect, method A showed higher bursting pressures than the other methods at 5 min and 3 h (p < 0.05); method B showed higher than methods C and D at 5 min and 3 h (p < 0.05). For the 12-mm square defect, method A showed higher bursting pressures than the other methods at all time points (p < 0.05). Moreover, method B showed higher than method C at 24 h (p < 0.05). Visceral pleural repairs using polyglycolic acid combined with fibrin glue showed the highest bursting pressure. Oxidized regenerated cellulose combined with fibrin glue showed sufficiently high bursting pressure in repair of small 6-mm circular defects.
Erfanian, Reza; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Darvishzadeh, Masoud; Zanjani, Leila Oryadi; Zadegan, Shayan Abdollah; Kamrani, Reza Shahryar
2014-01-01
The use of fibrin adhesives has a broad background in nerve repair. Currently the suboptimal physical properties of single- donor fibrin adhesives have restricted their usage. The present experiment studies the performance and physical characteristics of a modified fibrin glue prepared from single-donor human plasma in the repair of posterior tibial nerve of rat. Forty Wistar rats were divided into 5 groups; in the control group, tibial nerve was completely transected and no treatment was done, while in the four experimental groups the nerve stumps were reconnected by one suture, three sutures, one suture with fibrin glue and fibrin glue alone respectively. During 8 weeks of follow-up, Tibial Function Index was measured weekly and adhesive strength, inflammation and scar formation were assessed at the end of the study. Nerve stumps dehiscence rate and adhesive strength were similar in all experimental groups and significantly differed from control group (P<0.05). By the end of the eighth follow-up week, functional recovery of one and three sutures groups were significantly higher than groups in which fibrin glue was used for repair (P<0.05). The amount of inflammation and scar tissue formation was similar among all groups. The study results show that the prepared single-donor fibrin adhesive has acceptable mechanical properties which could provide required adhesiveness and hold nerve stumps in the long term; yet, we acknowledge that more studies are needed to improve functional outcome of single donor fibrin adhesive repair.
Fibrin glue as interposition graft for tarsal coalition.
Weatherall, Justin M; Price, Andrew E
2013-01-01
We describe a surgical technique and report outcomes for fibrin glue interposition after resection of a tarsal condition. An institutional review board--approved retrospective review of all pediatric patients with a tarsal coalition managed with resection was conducted between January 2002 and July 2010 by a single surgeon. All coalitions were resected with interposition of fibrin glue. Patients were evaluated for postoperative complications, pain, weight-bearing status, return to sports, and ankle and subtalar range of motion. Six feet without a coalition were used as a control group. Nine patients (12 feet) were identified with mean follow-up of 2.1 years (range, 7-72 months). Pre-operative complaints were predominantly foot and ankle pain. Patients also reported flatfeet and recurrent ankle sprains. There were no reported postoperative complications. All 9 patients were weight-bearing as tolerated and returned to sports by 6 months. Fibrin glue is a safe and reliable alternative to tissue grafts for interposition after resection of a tarsal coalition.
Lessons learned from laser tissue soldering and fibrin glue pyeloplasty in an in vivo porcine model.
Barrieras, D; Reddy, P P; McLorie, G A; Bägli, D; Khoury, A E; Farhat, W; Lilge, L; Merguerian, P A
2000-09-01
We compared sutured pyeloplasty to 2 newer techniques of tissue anastomosis, including laser soldered pyeloplasty using a diode laser with 50% albumin solder mixed with indocyanine green and fibrin glue. We performed 53 pyeloplasties in 50 pigs using suture, laser or fibrin glue. In the immediate group anastomotic leak pressure was measured immediately postoperatively, and then animals were euthanized. At 1, 3 and 4 weeks postoperatively a pressure flow study at 10 cc per minute in cm. H2O was performed, and tissue was sent for histological and collagen content analysis. In the immediate studies laser soldering achieved a significantly higher mean anastomotic leak pressure (50.5 +/- 15.1 cm. H2O) than sutured (17.3 +/- 5.4) or fibrin glued (3.5 +/- 1.5) repairs. In the 1, 2 and 4-week studies animals in the sutured pyeloplasty group had no complications, and all pressure flow studies except 1 were normal. However, in the laser soldered groups we observed 8 urinomas in 19 animals, and most occurred during the first part of our study. This complication was prevented by stopping urine flow at the anastomotic site at laser irradiation and by improving application of the solder. Of the 11 animals in which pressure flow studies were performed only 2 were obstructed. Of the 7 chronic fibrin glue group 4 animals had urinomas and 2 had unobstructed pressure flow studies. Histological studies and immunohistochemical staining for collagen showed no differences in collagen distribution among the 3 procedures. Laser soldering and fibrin glue pyeloplasties are not superior in the long-term compared to sutured pyeloplasty. Fibrin glue in our animal model had the highest failure rate. Further improvements in the technical aspect of laser tissue welding need to be made to benefit from its theoretical advantages in minimally invasive surgery.
Tachibana, Mitsuo; Kinugasa, Shoichi; Yoshimura, Hiroshi; Dhar, Dipok Kumar; Ueda, Shuhei; Fujii, Toshiyuki; Kohno, Hitoshi; Nagasue, Naofumi
2003-07-01
Fibrin glue has been shown to be effective in improving postoperative chylothorax following various thoracic procedures and in reducing lymphorrhea after axillary dissection. It is unknown, however, whether fibrin glue is effective in reducing lymph leakage (pleural effusion) after esophagectomy. A series of 43 consecutive patients with thoracic esophageal cancer who underwent extended esophagectomy were prospectively randomized to two groups: group A (n = 21), in whom 3 ml of fibrin glue was applied to the dissected mediastinum; and group B (n = 22), in whom fibrin glue was not applied. The time of drain removal and the volume of the thoracic drainage were compared. All data were expressed as the mean +/- standard deviation. There were no significant differences in the clinicopathologic characteristics between the two groups. None of the patients developed chylothorax or died during their hospital stay. The daily volume from the thoracic drain (457 +/- 273 ml) was significantly (p < 0.05) larger on postoperative day (POD) 1 in group A than in group B (298 +/- 158 ml) and tended to be larger (p < 0.10) on PODs 4 and 6 in group A than in group B. The cumulative drainage volume was significantly (p < 0.05) larger on PODs 4 to 6 and POD 9, and it tended to be larger (p < 0.10) on PODs 1, 3, 7, 8, 10, and 11 in group A than in group B, suggesting that the cumulative drainage volume in group A was consistently larger than that in group B. The cumulative numbers of patients with a drain remaining in place were not significantly different for the two groups (p = 0.4683). Three patients in group A, however, had prolonged insertion (> 20 days) of the chest tube. There were no significant differences in the incidence of postoperative chest-related complications. No patients in group A developed viral infectious disease during the long-term follow-up. Application of fibrin glue to the dissected mediastinum seems to induce postoperative lymph leakage and thus be responsible for prolonged chest tube insertion in some patients. Hence the use of fibrin glue cannot be recommended for reducing lymph leakage after esophagectomy.
Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs.
Djenić, Nebojša; Višnjić, Milan; Dragović, Saša; Bojanić, Vladmila; Bojanić, Zoran; Djurdjević, Dragan; Djindjić, Boris; Kostov, Miloš
2015-09-01
Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the war-surgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach). Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics (ceftriaxone and clindamycin) was applied. The use of this method should be limited to individual and strictly controlled cases in civil practice for now.
Usefulness of a New Gelatin Glue Sealant System for Dural Closure in a Rat Durotomy Model
KAWAI, Hisashi; NAKAGAWA, Ichiro; NISHIMURA, Fumihiko; MOTOYAMA, Yasushi; PARK, Young-Su; NAKAMURA, Mitsutoshi; NAKASE, Hiroyuki; SUZUKI, Shuko; IKADA, Yoshito
2014-01-01
Watertight dural closure is imperative after neurosurgical procedures, because inadequately treated leakage of cerebrospinal fluid (CSF) can have serious consequences. We used a rat durotomy model to test the usefulness of a new gelatin glue as a dural sealant in a rat model of transdural CSF leakage. All rats were randomly divided into one of the following three treatment groups: no application (control group: N = 18), application of fibrin glue (fibrin glue group: N = 18), and application of the new gelatin glue (new gelatin glue group: N = 18). The craniotomy side was re-opened, and CSF leakage was checked and recorded at 1, 7, and 28 days postoperatively. The new gelatin glue was adequate for stopping CSF leakage; no leakage was observed at postoperative days 1 or 7, and leakage was observed in only one rat at postoperative day 28. This result was statistically significant when compared to the control group (P = 0.002, P = 0.015, P = 0.015, respectively). The pathologic score of the new gelatin group was not different from that of the control or fibrin glue groups. We conclude that our new gelatin glue provides effective watertight closure 1, 7, and 28 days after operation in the rat durotomy model. PMID:25070015
Cappabianca, Paolo; Esposito, Felice; Magro, Francesco; Cavallo, Luigi Maria; Solari, Domenico; Stella, Lucio; de Divitiis, Oreste
2010-05-01
The objective of this study is to report our experience and illustrate our technique in the use of fibrin glue in the treatment of post-operatory cerebrospinal fluid (CSF) leaks and collections following different neurosurgical procedures. In a 3-year period, 40 subjects underwent endoscopic endonasal approach for different sellar and skull base lesions (three tuberculum sellae meningiomas, six craniopharyngiomas, three Rathke's cleft cysts and 28 pituitary macroadenomas), in which an intraoperative CSF leakage was evident. In such subjects, the fibrin glue was used as a first step of the final phase of the procedure-i.e. the reconstruction of the skull base defect-followed by the other materials employed. Furthermore, ten other patients, who had undergone transsphenoidal (four cases), spinal (two cases), posterior fossa (three cases) and transcortical intraventricular tumour removal (one case) neurosurgical procedures and developed CSF leaks or collections, were conservatively treated by single or repeated in situ injections of "modified" fibrin glue under local anaesthesia according to different described techniques. In total, 50 patients constitute the clinical material of the present study. In the cases where the fibrin glue was used during the reconstruction phase of the procedure (40 cases), the glue was injected inside the tumour cavity to fill the dead space left by the removal of the lesion. In case of post-operative CSF leak or CSF fluid collection (ten cases), after discarding 50-80% of the thrombin solution to obtain prevalence of the product's adhesive properties, fibrin glue was injected directly in the path of the CSF leak or into the collection cavity after aspiration of the collection's content. This was performed with the provided application system or through lumbar or Tuohy needles. Applications were repeated every 48 h until the disappearance of the leak. In all the treated cases, the disappearance of CSF leaks or collections was obtained with a number of applications ranging from one to five. Successful results are stable with a follow-up ranging from 6 months to 3 years. In our experience, the injection of fibrin glue has proved to be effective in filling or sealing post-operative "dead spaces" and treating minor or initial CSF leaks resulting from procedures of transsphenoidal, cranial and spinal surgery, adding another possibility in the management of many of these dreadful complications.
Fibrin Glue Used as an Adhesive Agent in CNS Tissues
Cheng, Henrich; Almström, Susanne; Olson, Lars
1994-01-01
One of the limitations of many bridging experiments in neural transplantation is that the CNS tissues cannot be sutured. Fibrin glue is a two-component system derived from whole blood which, when mixed, reproduces the final stage of blood coagulation and solidifies. Many experimental studies of humans and animals show that fibrin glue repair of peripheral nerves is almost equivalent to microsurgical sutures. In this study, we attempted to extend its use to CNS tissues and transplants. Two techniques were tried: (1) Bilateral parietal knife cuts were performed by stereotaxic technique in six rats. Fibrin glue was applied in the right-side cortical lesion. Immunohistochemistry using antisera to tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), laminin and neurofilament (NF) was essentially similar between the control and treatment groups. The immunoreactivity of each marker revealed no significant differences between the two groups on days 1, 7 and 30. There was no difference in terms of gliosis or microvascular proliferation. (2) Embryonic day 16 fetal locus coeruleus was grafted together with E16 cortex to the anterior chamber of sympathectomized eyes. In the six eyes of the glue treatment group, the parietal cortical piece and the locus coeruleus piece were joined together before grafting by immersing them in the solution of fibrin glue. In the eight eyes of the control group, pieces of parietal cortex and locus coeruleus were introduced individually and approximated by gently pressing the cornea. The sizes of double grafts showed no significant difference between groups during six weeks postgrafting. The immunohistochemical pictures using antisera against TH, GFAP and laminin were similar in both groups. Catecholaminergic fibers from the grafted locus coeruleus were found bridging over into the parietal cortical piece in both the control and treatment groups. There was no significant difference in TH-positive nerve fiber density between tissue glue joined and control double intraocular grafts. In conclusion, fibrin glue can be used as an adhesive agent in CNS tissues without hampering the outgrowth of neurites or causing adverse tissue reactions in fetal or adult nervous tissues. PMID:7578439
Lim, Ju Hyun; You, Dalsan; Jeong, In Gab; Park, Hyung Keun; Ahn, Hanjong; Kim, Choung-Soo
2013-10-01
Vesicourethral anastomotic urine leak is a common postoperative complication of radical prostatectomy. Herein we describe a novel method for the treatment of this complication. Intervention for a prolonged or massive anastomotic urine leak was required in 10 out of 1828 patients (0.5%) submitted to radical prostatectomy between 2007 and 2011. N-butyl-2-cyanoacrylate (Histoacryl) followed by fibrin glue (Greenplast) were injected under local anesthesia into vesicourethral anastomotic gaps under fluoroscopic guidance using a 20-Fr rigid cystoscope. Cystograms were taken in all patients to confirm complete urine leak resolution before the removal of the urethral catheter. Cystoscopic injection of Histoacryl followed by fibrin glue was technically successful and well tolerated in all patients. The mean time from radical prostatectomy to glue injection was 16.0 days (range 12-27 days). Urethral catheterization was required for an average of 7.7 days after cystoscopic injection of fibrin glue (range 3-13 days). These measures ultimately enabled complete resolution of the urine leak in all cases. At a mean follow up of 23.3 months, all 10 patients were fully continent. The mean time to recovery of urinary continence was 20.4 weeks (range 3.9-60.0 weeks). Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue into the anastomotic gap is both a feasible and effective solution in patients with a persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy. © 2013 The Japanese Urological Association.
Results of fibrin glue application therapy in testicular hydrocele.
Sirpa, A; Martti, A O
1998-01-01
Nine patients, mean age 55 years, with testicular hydroceles, were treated by aspiration and two-component fibrin glue injection. One patient was treated twice. The glue contains 70-110 mg fibrinogen and 500 IU human thrombin in 0.5- and 2-ml injections, respectively (Tisseel duo quick, Immune AB). The smaller glue volume was used in 4 cases and the larger volume in 6 cases. The average volume of hydrocele fluid was 77 (range 60-120) ml. Treatment caused no pain or discomfort other than puncture of the skin and no pain-relieving medication was required afterwards. In this series there were no infections but one conservatively treated hematoma. The hydrocele of that patient disappeared. Although the hydroceles recurred in 9 cases during the mean follow-up of 3.5 months, in 2 patients the hydroceles were clinically smaller than the original one and symptoms were milder subjectively. Our findings suggest that fibrin-adhesive glue is not sufficiently effective in treatment of testicular hydroceles.
Ohira, Suguru; Doi, Kiyoshi; Yaku, Hitoshi
2016-04-05
We describe a simple method to fix the great saphenous vein graft (SVG) to the right coronary artery along the atrioventricular groove using fibrin glue in off-pump coronary artery bypass grafting (OPCAB). After completion of the proximal anastomosis, the SVG was placed along the atrioventricular groove to the acute margin. Fibrin glue was sprayed using pressurized carbon dioxide gas. A distal anastomosis was subsequently performed after rotating the heart to expose the posterior descending artery. It is a straightforward and reproducible technique to determine the optimal length of the SVG and prevent kinking or stretching of the graft, especially in OPCAB.
He, Jie; Yang, Xiang; Yue, Peng-ju; Wang, Guan-yu; Guo, Ting; Zhao, Jian-ning
2009-07-01
To investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering. Chondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect. Grossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one. Complicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering.
Segura-Castillo, José L; Aguirre-Camacho, Humberto; González-Ojeda, Alejandro; Michel-Perez, Jorge
2005-01-01
A major complication in 30% to 75% of cases of surgical treatment of alveolar cleft is resorption of the bone graft. A treatment alternative is the application of fibrin glue, which has the capacity to favor the integration of the graft. The main objective of the study was to evaluate if the use of the fibrin glue reduces bone resorption when it is applied locally. The authors designed a randomized clinical trial. Patients were divided into two groups: group 1, fibrin glue; and group 2, control. Pre- and postoperative graft volume, bone density, bone quality (Lekholm and Zarb, and Norton and Gamble classifications), and postoperative complications were evaluated. The follow-up for all patients was 3 months after discharge. Twenty-seven patients were surgically treated, 13 in group 1 and 14 in group 2. Group 1 had increased graft volume compared with group 2 (64.32 cm v 21.70 cm; P < 0.0001). Bone density was higher in group 1 than in group 2 (396.57 v 245.68; P > 0.076). Bone quality was type 1, 2 and 3 and 4 in group 1. Resorption in group 2 was 62.26%; in group 1, it was 29.72% (P > 0.081). The observed complications were infection and dehiscence of sutures (P > 0.537). The authors conclude that the fibrin glue significantly diminishes bone resorption, allowing improved graft integration and quality.
Healing of rabbit calvarial critical-sized defects using autogenous bone grafts and fibrin glue.
Lappalainen, Olli-Pekka; Korpi, Riikka; Haapea, Marianne; Korpi, Jarkko; Ylikontiola, Leena P; Kallio-Pulkkinen, Soili; Serlo, Willy S; Lehenkari, Petri; Sándor, George K
2015-04-01
This study aimed to evaluate ossification of cranial bone defects comparing the healing of a single piece of autogenous calvarial bone representing a bone flap as in cranioplasty compared to particulated bone slurry with and without fibrin glue to represent bone collected during cranioplasty. These defect-filling materials were then compared to empty control cranial defects. Ten White New Zealand adult male rabbits had bilateral critical-sized calvarial defects which were left either unfilled as control defects or filled with a single full-thickness piece of autogenous bone, particulated bone, or particulated bone combined with fibrin glue. The defects were left to heal for 6 weeks postoperatively before termination. CT scans of the calvarial specimens were performed. Histomorphometric assessment of hematoxylin-eosin- and Masson trichrome-stained specimens was used to analyze the proportion of new bone and fibrous tissue in the calvarial defects. There was a statistically significant difference in both bone and soft tissue present in all the autogenous bone-grafted defect sites compared to the empty negative control defects. These findings were supported by CT scan findings. While fibrin glue combined with the particulated bone seemed to delay ossification, the healing was more complete compared to empty control non-grafted defects. Autogenous bone grafts in various forms such as solid bone flaps or particulated bone treated with fibrin glue were associated with bone healing which was superior to the empty control defects.
Ayhan, Baris; Erikoglu, Mehmet; Tavli, Süleyman S; Toy, Hatice
2012-08-04
Anastomotic leaks constitute one of the most serious intraoperative complications and although many studies have been devoted to finding a solution for this problem, none of them has yet been able offer a decisive, successful method. In this study, the ability of fibrin glue and adhesive film to repair anastomotic leaks in an experimental model was compared. The sample comprised four groups of seven rats: Group 1 (Control): the distal colon was transected and anastomosis was performed. Group 2 (Primary repair): incomplete anastomosis produced a leak that was closed by primary repair on day 3. Group 3 (Fibrin glue): incomplete anastomosis produced a leak that was closed by primary repair and fibrin glue applied on day 3. Group 4 (Adhesive film): incomplete anastomosis produced a leak that was closed by primary repair and adhesive film was applied on day 3. The rats were sacrificed on day 6 following anastomosis. Anastomotic blast compressions were measured and fibroblast activation, inflammation, neovascularization and levels of collagen were evaluated. The results from Group 4 showed that blast compression values were high and statistically significantly increased over control values (p < 0.05). Inflammation in Group 2 was significantly higher than the other groups (p < 0.05). No significant differences were detected in the comparison of the groups regarding the other scoring criteria (p > 0.05). Adhesive film is more effective in reducing anastomotic leakage than fibrin glue.
Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits.
Kivelio, A; Dekoninck, P; Perrini, M; Brubaker, C E; Messersmith, P B; Mazza, E; Deprest, J; Zimmermann, R; Ehrbar, M; Ochsenbein-Koelble, N
2013-12-01
Iatrogenic preterm prelabour rupture of fetal membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. The aim of this study was to evaluate the sealing capability and tissue interaction of mussel-mimetic tissue adhesive (mussel glue) in comparison to fibrin glue on punctured fetal membranes in vivo. A mid-gestational rabbit model was used for testing the materials. The fetal sacs of pregnant rabbits at day 23 were randomly assigned into experimental groups: unoperated (negative control), unclosed puncture (positive control), commercially available fibrin glue (FG) with decellularized amnion scaffold (DAM), mussel glue (MG) with DAM, or mussel glue alone. Evaluation was done at term (30 days' gestation) assessing fetal survival, fetal membrane integrity and histology of the membranes. Fetal survival was not significantly lower in any of the treatment groups compared to the negative control. All plugging materials could be found at the end of the pregnancy and no adverse effects on the fetus or the pregnant does could be observed. Sac integrity was higher in all treatment groups compared to the positive control group but significant only in the FG+DAM group. Cellular infiltration could be seen in fibrin glue and DAM in contrast to mussel glue which was only tightly adhering to the surrounding tissue. These cells were mostly of mesenchymal phenotype staining positive for vimentin. CD68 positive macrophages were found clustered around all the plugging materials, but their numbers were only significantly increased for the mussel glue alone group compared to negative controls. Mussel glues performance in sealing fetal membranes in the rabbit model was comparable to that of fibrin glue. Taking into account its other favorable properties, it is a noteworthy candidate for a clinically applicable fetal membrane sealant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Endoscopic treatment with fibrin glue of post-intubation tracheal laceration
Cascone, Roberto; Di Natale, Davide; Pierdiluca, Matteo; Mastromarino, Rossella; Natale, Giovanni; De Ruberto, Emanuele; Messina, Gaetana; Vicidomini, Giovanni; Santini, Mario
2017-01-01
Post-intubation tracheal laceration (PITL) is a rare and potential life-threatening condition requiring prompt diagnosis and treatment. A conservative treatment is indicated in patients with laceration <2 cm in length while surgery is the treatment of choice for laceration >4 cm. For laceration between 2–4 cm, the best treatment is debate; some authors recommend surgery while others do not definitely exclude endoscopic treatment. Herein, we reported the endoscopic treatment with fibrin glue of PITL. The procedure is performed using a standard video-bronchoscopy in operating room; the patient is in spontaneous breathing and deep sedation. After identification of tracheal laceration, the fibrin glue is injected through a dedicated double lumen catheter into the lesion. After mixing both components of fibrin glue, polymerization of fibrin occurs resulting in an elastic and opaque clot that closes the lesion. The key success of the procedure is based on accurate patient selection. Patients are eligible if (I) they are clinically stable and in spontaneous respiration; (II) with a small and superficial tracheal laceration (≤4 cm in length and without oesophageal injury); (III) localized at level of the upper or middle trachea; and (IV) without clinical and/or radiological signs of mediastinal collection, of emphysema or pneumomediastinum progression, and of infection. PMID:29078663
Zloto, Ofira; Alezra, Dror; Sagiv, Oded; Belkin, Michael; Dai, Vicktoria Vishnevskia; Moroz, Iris; Greenberg, Gahl; Ben-Artsi, Elad; Fabian, Ido Didi
2015-11-01
To examine a novel biological adhesive and dissolvent system for plaque placement and removal using fibrin glue and urokinase, respectively, in an in vivo animal model. The study was performed on 23 rabbit eyes. Of these, eight underwent a technical feasibility study and ultrasonographic plaque displacement measurements, nine were examined clinically and by magnetic resonance imaging and histopathology for tissue reaction to the biological substances used, and in six the impact of fibrin glue as an orbital space occupier on intraocular pressure was assessed. In an additional ex vivo experiment, the glue's radiation attenuating properties were tested using an oncology EDR2 film. Plaque horizontal movement throughout follow-up (7-10 days) was negligible (0.5 ± 0.2 mm), and there was no tilting whatsoever. In the tissue response experiment, no adverse effects were recorded after application of fibrin or urokinase throughout the 21-day follow-up period. Interestingly, a circumscribed local inflammatory response was noted in tissue surrounding the fibrin glue, and persisted at 21 days. In the orbital space-occupying experiment, application of 1 cc fibrin glue did not cause a significant elevation in intraocular pressure (IOP) (P = 0.06), and in the ex vivo experiment, there was no significant difference between radiation readings with and without glue separation of the radioactive sources and film (P = 0.065). The adhesive and dissolvent system was feasible and safe for plaque placement and removal. It may be superior to conventional surgical plaque placement methods in eliminating the relatively common risk of plaque tilting and complications due to scleral suturing.
Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue
Yin, Houfa; Qiu, Peijin; Wu, Fang; Zhang, Wei; Teng, Wenqi; Qin, Zhenwei; Li, Chao; Zhou, Jiaojie; Fang, Zhi; Tang, Qiaomei; Fu, Qiuli; Ma, Jian; Yang, Yabo
2016-01-01
The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations. PMID:27651001
Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue.
Yin, Houfa; Qiu, Peijin; Wu, Fang; Zhang, Wei; Teng, Wenqi; Qin, Zhenwei; Li, Chao; Zhou, Jiaojie; Fang, Zhi; Tang, Qiaomei; Fu, Qiuli; Ma, Jian; Yang, Yabo
2016-09-21
The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations.
Study of a novel three-dimensional scaffold to repair bone defect in rabbit.
Chen, Yushu; Bai, Bo; Zhang, Shujiang; Ye, Jing; Zhai, Haohan; Chen, Yi; Zhang, Linlin; Zeng, Yanjun
2014-05-01
Both decalcified bone matrix (DBM) and fibrin gel possess good biocompatibility, so they are used as scaffolds to culture bone marrow mesenchymal stem cells (BMSCs). The feasibility and efficacy of using compound material being made of decalcified bone matrix and fibrin gel as a three-dimensional scaffold for bone growth were investigated. BMSCs were isolated from the femur of rabbit, then seeded in prepared scaffolds after incubation for 28 days in vitro. In vivo: 30 New Zealand White Rabbits received bone defect in left radius and divided three treatment groups randomly: (1) BMSCs/decalcified bone matrix/fibrin glue as experimental group; (2) decalcified bone matrix/fibrin glue without cells as control group; (3) nothing was implanted into the bone defects as blank group. The observation period of specimens was 12 weeks, and were analyzed bone formation in terms of serum proteomics (2D-PAGE and MALDI-TOF-TOF-MS), hematoxylin-eosin (HE) staining, ALP staining, and Osteopontin immunofluorescence detection. The experimental group present in three peculiar kinds of proteins, whose Geninfo identifier (GI) number were 136466, 126722803, and 126723746, respectively, correspond to TTR protein, ALB protein, RBP4 protein, and the histological inspections were superior to the other group. The content of osteopontin in experimental group was significantly higher than control group (p < 0.05). The overall results indicated that a combined material being made of BMSCs/decalcified bone matrix/fibrin glue can result in successful bone formation and decalcified bone matrix/fibrin glue admixtures can be used as a scaffold for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.
Whyte, Graeme P; McGee, Alan; Jazrawi, Laith; Meislin, Robert
2016-05-01
To evaluate the fixation integrity at time zero of a type I/III collagen patch secured to a chondral defect in the porcine knee using methods typically employed in autologous chondrocyte implantation (ACI) and matrix-assisted chondrocyte implantation. Twenty-four porcine knee specimens underwent a medial parapatellar arthrotomy. A prefabricated template was used to create cartilage defects of 2 cm(2) in the medial femoral condyle. A size-matched collagen patch was fashioned. Four methods of fixation to the chondral defect were analyzed: group 1-saline, group 2-fibrin glue around the periphery of the patch, group 3-fibrin glue applied to the base of the defect and around the periphery of the patch, group 4-6-0 vicryl suture and fibrin glue around the periphery of the patch. Collagen patch fixation was assessed at intervals of 60, 300, 600, 900, and 1,200 cycles from full extension to 90° of flexion, performed manually without application of axial force. Patch fixation was evaluated by 2 independent observers using a customized scoring scale. Mean peripheral detachment of the patch and chondral defect uncovering remained less than 25% for all groups. Area of defect uncovering was significantly increased in group 2 compared with group 4 after 900 and 1,200 cycles (P = .0014 and P = .0025, respectively). Fibrin glue applied to the base of the defect, or suturing of the patch, reduced deformation significantly after 900 cycles. Suture increases the stability of fixation of a type I/III collagen patch to a chondral defect better than fibrin glue alone in the porcine knee after repetitive cycling, with respect to patch detachment and chondral defect uncovering. Application of fibrin glue to the base of the defect, or securing the patch with suture, decreases collagen patch deformation. In cases where minimally invasive techniques do not allow suture fixation of the collagen patch, scaffold fixation may be compromised during articular motion protocols typically used after second- and third-generation ACI procedures. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura
2015-01-01
Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients’ distress and costs to the health system. PMID:25369587
Cravens, Matthew G; Behn, Anthony W; Dragoo, Jason L
2017-11-01
Fibrin glues are widely used in orthopedic surgery as adhesives and hemostatic agents. We evaluated the compressive properties of selected fibrin glues in order to identify which are appropriate for tissue regeneration applications subject to compression. Uniaxial unconfined compression tests were performed on fibrin gels prepared from commercial and autologous products: (1) Evicel (Ethicon), (2) Tisseel (Baxter), (3) Angel (Arthrex), and (4) ProPlaz (Biorich). Cyclic loads were applied from 0 to 30% strain for 100cycles at 0.5Hz. Following cyclic testing, specimens were subjected to ramp displacement of 1% strain per second to 80% strain. Throughout cyclic loading, Evicel and Tisseel deformed (shortened) less than Angel at all but one time point, and deformed less than ProPlaz at cycles 10 and 20. The dynamic moduli, peak stress, and strain energy were significantly greater in Tisseel than all other groups. Evicel displayed significantly greater dynamic moduli, peak stress, and strain energy than Angel and ProPlaz. Following cyclic testing, Tisseel and Evicel were significantly less deformed than Angel. No specimens exhibited gross failure during ramp loading to 80% strain. Ramp loading trends mirrored those of cyclic loading. The tested commercial glues were significantly more resistant to compression than the autologous products. The compressive properties of Tisseel were approximately twice those of Evicel. All preparations displayed moduli multiple orders of magnitude less than that of native articular cartilage. We conclude that in knee surgeries requiring fibrin glue to undergo compression of daily activity, commercial products are preferable to autologous preparations from platelet-poor plasma, though both will deform significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.
Gong, Jingwen; Fan, Jiaqi; Shen, Ting; Jiang, Jin
2018-03-01
To assess long-term efficacy and safety of self-made cryopreservative fibrin glue (SMC) applied in pterygium surgery. Prospective, comparative, interventional case series. Forty eyes of 40 patients with nasal primary pterygium, 24 male and 16 female, were enrolled. The patients were assigned to two groups and each contained 12 male and eight female based on the pterygium area encroaching onto the cornea. In one group, the conjunctival autograft was attached to the sclera with SMC stored for 2 months, and in the other group, commercial fibrin glue kit (CK) was applied after the pterygium was removed. All the patients were followed up postoperatively on days 1, 3, 7 and 14 then at months 1, 3, 6, 12. The main outcome measures included operating time, postoperative discomfort, recurrence rate and complications. There were no significant differences in surgery time (p = 0.713) and postoperative discomfort (day 1, 3, 7; p = 0.747, p = 0.766, p = 0.983, respectively) between the two groups. By the end of 1-year follow-up, the recurrence rate was 0% in the SMC group and 5% in the CK group (p = 1.000). There were no infections and severe visual acuity (VA) threatening complications in either group. Self-made cryopreservative fibrin glue (SMC) is as effective as standard CK for autograft fixation in pterygium surgery and it also has good safety after long-term follow-up. For its convenience and low cost, this new methods should be popularized, especially in underdeveloped area. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Gubitosi, A; Moccia, G; Malinconico, F A; Docimo, G; Ruggiero, R; Iside, G; Avenia, N; Docimo, L; Foroni, F; Gilio, F; Sparavigna, L; Agresti, M
2009-01-01
The authors, on the basis of a long clinical experience with human fibrin glue in general surgery, compared two different extracellular matrix (collagen), Surgisis and TissueDura, with human fibrin glue, applied during the operation, and sometimes in postoperative, to obtain the healing of perianal fistulas. The collagenic extracellular matrix provides, according to the rationale suggested, an optimal three-dimensional structure for the fibroblastic implant and neoangiogenesis, hence for the fistula "fibrotizzation" and closure. The encouraging results for transphincteric fistulas and a simple and easy technique push to researchers on samples statistically significant.
Autologous fibrin glue: the last step in operative hemostasis.
Tawes, R L; Sydorak, G R; DuVall, T B
1994-08-01
Fibrin glue may be the perfect hemostatic agent for operative use as it seals in minutes, has no tissue toxicity, reabsorbs, and promotes local tissue growth and repair. Use in the United States has been limited because of lack of Food and Drug Administration approval of the commercial homologous products, lack of a concentrated source of fibrinogen, and because of the potential for viral transmission, particularly hepatitis, with pooled homologous plasma and cryoprecipitate-based methods. Autologous fibrin glue (AFG) obviates these problems. During the past year, we obtained AFG through the same routine predonation procedure as with red blood cells before major elective surgery. Intraoperatively, we made AFG from the platelet-rich plasma derived from the Plasma-Saver. Our experience has been with 36 patients undergoing aortic, thoracoabdominal, and thoracic surgery, as well as patch graft angioplasty cases. Fibrin glue formation mimics the final stage in the coagulation cascade. The AFG from predonation acts more like an epoxy glue, while the AFG made during surgery is less viscous and acts more like a sealant because of the lesser concentration of fibrinogen in platelet-rich plasma. In emergencies, however, the intraoperative method is obviously the only choice available, and it is a useful adjunct to hemostasis at the end of the procedure. The technique will be described. This relatively new approach to hemostasis should gain popularity because it is easy and fairly inexpensive to produce, and because the patient's own blood is used.
Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane
Chaurasia, Shyam S.; Champakalakshmi, Ravi; Li, Ang; Poh, Rebekah; Tan, Xiao Wei; Lakshminarayanan, Rajamani; Lim, Chwee T.; Tan, Donald T.; Mehta, Jodhbir S.
2012-01-01
Background Corneal transplantation has rapidly evolved from full-thickness penetrating keratoplasty (PK) to selective tissue corneal transplantation, where only the diseased portions of the patient's corneal tissue are replaced with healthy donor tissue. Descemet's membrane endothelial keratoplasty (DMEK) performed in patients with corneal endothelial dysfunction is one such example where only a single layer of endothelial cells with its basement membrane (10–15 µm in thickness), Descemet's membrane (DM) is replaced. It is challenging to replace this membrane due to its intrinsic property to roll in an aqueous environment. The main objective of this study was to determine the effects of fibrin glue (FG) on the biomechanical properties of DM using atomic force microscopy (AFM) and relates these properties to membrane folding propensity. Methodology/Principal Findings Fibrin glue was sprayed using the EasySpray applicator system, and the biomechanical properties of human DM were determined by AFM. We studied the changes in the “rolling up” tendency of DM by examining the changes in the elasticity and flexural rigidity after the application of FG. Surface topography was assessed using scanning electron microscopy (SEM) and AFM imaging. Treatment with FG not only stabilized and stiffened DM but also led to a significant increase in hysteresis of the glue-treated membrane. In addition, flexural or bending rigidity values also increased in FG-treated membranes. Conclusions/Significance Our results suggest that fibrin glue provides rigidity to the DM/endothelial cell complex that may aid in subsequent manipulation by maintaining tissue integrity. PMID:22662156
Truong, S; Böhm, G; Klinge, U; Stumpf, M; Schumpelick, V
2004-07-01
The incidence of clinically relevant anastomotic leaks after upper gastrointestinal surgery is approximately 4% to 20%, and the associated mortality is up to 80%. Depending on the clinical presentation, the treatment options include surgery, conservative treatment with or without external drainage or endoscopic treatment. This report presents nine cases of anastomotic leaks or fistulae after surgery for upper gastrointestinal cancers that were treated by insertion of a Vicryl plug and sealing with fibrin glue. Under sedation, all nine patients underwent endoscopic lavage of the cavity at the site of anastomotic leakage. The entrance to the cavity then was filled with Vicryl mesh and sealed off with fibrin glue. After the procedure, the patients underwent endoscopy and a water-soluble contrast study for assessment of the result. Seven of the nine patients had complete healing of the anastomotic leak or fistula after one to two endoscopic treatments. In one case, the treatment failed immediately because of a large and direct tracheoesophageal fistula. Another patient experienced recurrent intrathoracic abscesses after initial technical success. Postoperative upper gastrointestinal fistulas or anastomotic leaks can be managed successfully with little morbidity by means of endoscopic insertion of Vicryl mesh with fibrin glue, thereby avoiding repetitive major surgery and its associated risks.
Maniwa, Tomohiro; Kaneda, Hiroyuki; Saito, Yukihito
2009-06-01
Pulmonary fistulas caused by tumours are very fragile and difficult to suture directly. It is impossible to close pulmonary fistulas with tissue sealants when massive air leakage occurs in the low pressure of the respiratory tract. A 73-year-old man with a pneumothorax caused by lung cancer had suffered a persistent massive air leakage for more than one month. We used a fibrin glue-soaked polyglycolic acid (PGA) sheet for sealing the complicated fistula. In addition, the visceral pleura of the fistula was wrapped with the pedicle of an intercostal muscle (ICM) flap to prevent massive air leakage. The pneumothorax did not reappear after surgery. Thus, a fibrin glue-soaked PGA sheet covered with an ICM flap was effective for sealing an intractable air-leaking fistula caused by lung cancer.
Comparison of fibrin glue and Vicryl sutures in conjunctival autografting for pterygium surgery.
Wang, Xiu; Zhang, Yan; Zhou, Lei; Wei, Ruihua; Dong, Lijie
2017-01-01
To compare clinical parameters and the tear levels of inflammatory cytokines between pterygium surgery using sutures or fibrin glue. Fifty-six patients with primary pterygium were divided into the suture group and the glue group, in which the autograft was secured with 10-0 Vicryl sutures and fibrin glue, respectively. A questionnaire, slit-lamp examination, Schirmer test, and visual acuity test were performed in all participants. Real-time quantitative PCR (q-PCR) was used to analyze the expression of genes in pterygium and healthy conjunctival tissues. Based on the qPCR results and literature reports, five inflammatory cytokines, including hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase 2 (MMP2), and tumor necrosis factor-α (TNF-α), were selected, and their protein levels were measured with enzyme-linked immunosorbent assay (ELISA) in patient tears before surgery as well as at postoperative day 1, 7, and 30. There are 28 patients in either the suture or the glue group. The average duration of surgery was 20.17 ± 3.23 min for the glue group and 32.42 ± 4.47 min for the suture group (p = 0.000). Visual acuity in both groups was improved (p = 0.002) after the surgical procedures. There were more symptoms in the suture group than in the glue group at postoperative day 7 (p = 0.002). Postoperative symptoms disappeared in both groups at 1 month after surgery. Recurrence was observed in one case in the glue group and in two cases in the suture group at the 6 month postoperative follow-up (p = 0.714). In comparison to the preoperative levels (4.33 ± 0.43 ng/ml for the suture group; 4.20 ± 0.26 ng/ml for the glue group), the levels of TNF-α in tears increased in the suture group (5.02 ± 0.49 ng/ml, p = 0.016) and decreased in the glue group (3.84 ± 0.35 ng/ml, p = 0.052) on postoperative day 1. The glue treatment induced higher HGF production (4.78 ± 1.25 ng/ml) than the suture treatment (3.04 ± 1.18 ng/ml) at postoperative day 1 (p = 0.020). Higher levels of TGF-β1 in the glue group were detected at postoperative day 1 (3.71 ± 0.18 ng/ml) and postoperative day 30 (4.50 ± 0.51 ng/ml), compared to those in the suture group, respectively (2.74 ± 0.21 ng/ml, p = 0.000 for day 1; 3.36 ± 0.96 ng/ml, p = 0.017 for postoperative day 30). Fibrin glue is effective and safe for attaching conjunctival autografts with an easy surgical procedure, shortened operating time, and less postoperative discomfort. In the early postoperative period, the protein expression of inflammatory cytokines implicates that fibrin glue may induce accelerated healing and subdued inflammation on the ocular surface compared to sutures.
Intraoperative use of fibrin glue dyed with methylene blue in surgery for branchial cleft anomalies.
Piccioni, Michela; Bottazzoli, Marco; Nassif, Nader; Stefini, Stefania; Nicolai, Piero
2016-09-01
We present a new method of optimizing the results of surgery for branchial cleft anomalies based on the intraoperative injection of fibrin glue combined with methylene blue dye. Retrospective single-center cohort study. The method was applied in 17 patients suffering from branchial anomalies. Six (35.29%) had a preauricular lesion; three (17.65%) had lesions derived from the first arch/pouch/groove (type I), four (23.53%) had lesions derived from the first (type II), one (5.88%) had lesions derived from the second, one (5.88%) had lesions derived from the third, and two (11.76%) had lesions derived from the fourth. The median and mean age at surgery were 10 and 10.6 years, respectively. All patients were followed by periodic clinical and ultrasonographic examination. The combination of fibrin glue with methylene blue facilitated the correct assessment of the extension of the lesions and their intraoperative manipulation. After a mean follow-up of 47.8 months, all patients were free of disease. Intraoperative injection of branchial fistulae and cysts by a mixture of fibrin glue and methylene blue is an effective, easy, and safe tool to track lesions and achieve radical resection. The technique requires a definitive validation on a large cohort with adequate stratification of patients. 4 Laryngoscope, 126:2147-2150, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
Chen, W-l; Huang, Z-q; Chai, Q; Zhang, D-m; Wang, Y-y; Wang, H-j; Wang, L; Fan, S
2011-06-01
Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Sutureless amniotic membrane transplantation for partial limbal stem cell deficiency.
Kheirkhah, Ahmad; Casas, Victoria; Raju, Vadrevu K; Tseng, Scheffer C G
2008-05-01
To evaluate the results of sutureless amniotic membrane (AM) transplantation using fibrin glue for reconstructing corneal surfaces with partial limbal stem cell deficiency (LSCD). Retrospective noncomparative interventional case series. Eleven eyes of nine patients that had LSCD with 120 degrees to almost 360 degrees of limbal involvement underwent superficial keratectomy to remove the conjunctivalized pannus followed by AM transplantation using fibrin glue. Additional sutureless AM patch (ProKera; Bio-Tissue, Inc, Miami, Florida, USA) was used in seven patients, and mitomycin C was applied on the cornea in four eyes and during fornix reconstruction in seven eyes. The surgery was repeated in three eyes for residual pannus. During a mean follow-up of 14.2 +/- 7.7 months (range, six to 26 months), all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect, and showed less stromal cloudiness and vascularization. Best-corrected visual acuity improved in nine eyes (81.8%). Corneal epithelialization proceeded by epithelial growth over AM (n = 4), accompanied by dissolution of AM (n = 4) or a combination of both (n = 3). No complication was noted regarding initial or repeated uses of fibrin glue. AM transplantation using fibrin glue appears to be a safe and effective method of restoring a stable corneal epithelium for cases with partial LSCD. This approach avoids the need of transplanting limbal epithelial stem cells.
Jung, Sung-No; Rhie, Jong Won; Kwon, Ho; Jun, Young Joon; Seo, Je-Won; Yoo, Gyeol; Oh, Deuk Young; Ahn, Sang Tae; Woo, Jihyoun; Oh, Jieun
2010-03-01
Human adipose-derived mesenchymal stem cells (MSCs) were differentiated into chondrogenic MSCs, and fibrin glue was used together to explore the feasibility of whether cartilages can be generated in vivo by injecting the differentiated cells. Mesenchymal stem cells extracted from human adipose were differentiated into chondrogenic MSCs, and such differentiated cells mixed with fibrin glue were injected subcutaneously into the back of the nude mouse. In addition to visual evaluation of the tissues formed after 4, 8, and 12 weeks, hematoxylin-eosin staining, Masson trichrome staining, measurement of glycosaminoglycan concentration using dimethylmethylene blue, agreecan through reverse transcriptase-polymerase chain reaction, type II collagen, and expression of SOX-9 were verified. Moreover, the results were compared with 2 groups of controls: 1 control group that received only injection of chondrogenic-differentiated MSC and the supporting control group that received only fibrin glue injection. For the experimental group, cartilage-like tissues were formed after 4, 8, and 12 weeks. Formation of cartilage tissues was not observed in any of 4, 8, and 12 weeks of the control group. The supporting control group had only a small structure formation after 4 weeks, but the formed structure was completely decomposed by the 8th and 12th weeks. The range of staining dramatically increased with time at 4, 8, and 12 weeks in Masson trichrome staining. The concentration of glycosaminoglycan also increased with time. The increased level was statistically significant with more than 3 times more after 8 weeks compared with 4 weeks and more than 2 times more after 12 weeks compared with 8 weeks. Also, in reverse transcriptase-polymerase chain reaction at 4, 8, and 12 weeks, all results expressed a cartilage-specific gene called aggrecan, type II collagen, and SOX-9. The study verified that the chondrogenic-differentiated MSCs derived from human adipose tissues with fibrin glue can proliferate and form new cartilage. Our findings suggest that formation of cartilages in vivo is possible.
Chen, Wei-liang; Zhang, Li-ping; Huang, Zhi-quan; Zhou, Bin
2013-12-01
We evaluated the curative effect of fibrin glue combined with OK-432 (streptococcal pyrogenic exotoxin A, Picibanil™) and bleomycin on 9 patients with sialoceles after parotidectomy. The primary lesions included pleomorphic adenomas in 6 cases and Warthin's tumours in 3 cases. After a sialocele had been diagnosed each patient had repeated aspirations and pressure dressings for 3-4 weeks, but these treatments failed. The patients were then treated with percutaneous sclerotherapy with the injection of fibrin glue 8-10 ml combined with OK-432 5 mg and bleomycin 15 mg. All the sialoceles disappeared completely after a single procedure in 2-3 weeks. The patients have been followed up for more than 6 months with no evidence of recurrent sialocele or injury to the facial nerve related to sclerotherapy. This simple, safe technique can be successfully used to treat sialoceles after parotidectomy. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Huang, Yun-Chen; Peng, Steve Shinn-Forng; Hsu, Wei-Chung
2016-06-01
This study aims to assess the efficacy of a novel endoscopic management for congenital pyriform sinus fistula (CPSF) using potassium titanyl phosphate (KTP) laser assisted endoscopic tissue fibrin glue biocauterization in children. From 2010 to 2014, a total of 5 children with recurrent or acute suppurative thyroiditis or neck abscess secondary to CPSF were enrolled retrospectively in this study. Mean age at the first time of endoscopic biocauterization was 6.2 ± 0.7 (5-7) years. The barium swallow study detected a fistula in four cases. Endoscopy identified an internal opening at the pyriform sinus in all cases with four on the left side and one on the right side. All patients underwent KTP laser assisted endoscopic tissue fibrin glue biocauterization as treatment for CPSF. Only one case required the second endoscopic procedure due to fluctuation of symptoms. Post-endoscopic follow-up duration of these patients was 24.6 ± 11.6 (7-36) months. Neither complications nor recurrences were noted during follow-up in all patients. For children presenting with repeated acute suppurative thyroiditis or neck infections, clinicians should highly suspect the possibility of CPSF. Endoscopy should be performed not only to confirm the diagnosis but also could be served as an initial treatment modality of biocauterization by KTP laser and tissue fibrin glue, which was demonstrated as a less invasive, safe, and effective method in children. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Effectiveness of a new gelatin sealant system for dural closure.
Kawai, Hisashi; Nakagawa, Ichiro; Nishimura, Fumihiko; Motoyama, Yasushi; Park, Young-Su; Nakamura, Mitsutoshi; Nakase, Hiroyuki; Suzuki, Shuko; Ikada, Yoshito
2014-10-01
Watertight dural closure is imperative after neurosurgical procedures because inadequately treated leakage of cerebrospinal fluid (CSF) can have serious consequences. In this study, the authors test the use of a new gelatin glue as a dural sealant in in vitro and in vivo canine models of transdural CSF leakage. The in vitro model was sutured semicircles of canine dura mater and artificial dural substitute. The sutures were sealed with gelatin glue (n = 20), fibrin glue (n = 20), or a polyethylene glycol (PEG)-based hydrogel sealant (n = 20). Each sample was set in a device to measure water pressure, and pressure was increased until leakage occurred. Bonding strength was subjectively evaluated. The in vivo model was dogs who underwent dural excision and received either no sealant (control group; n = 5) or gelatin glue sealant (n = 5) before dural closure. Twenty-eight days post-surgery, the maximum intracranial pressure was measured at the cisterna magna using Valsalva maneuver and tissue adhesion was evaluated. The water pressure at which leakage occurred in the in vitro model was higher with gelatin glue (76·5 ± 39·8 mmHg) than with fibrin glue (38·3 ± 27·4 mmHg, P < 0·001) or the PEG-based hydrogel sealant (46·3 ± 20·9 mmHg, P = 0·007). Bonding strength was higher for the gelatin glue than fibrin glue (P < 0·001) or PEG-based hydrogel sealant (P = 0·001). The maximum intracranial pressure in the in vivo model was higher for the gelatin glue group (59·0 ± 2·2 mmHg) than the control group (13·8 ± 4·0 mmHg, P < 0·001). Tissue adhesion was lower for the gelatin glue group than the control group (P = 0·005). The new gelatin glue provides an effective watertight closure when used as an adjunct to sutured dural repair.
Barbizan, Roberta; Castro, Mateus V.; Barraviera, Benedito; Ferreira, Rui S.; Oliveira, Alexandre L. R.
2014-01-01
The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results. PMID:25157845
Surgical adhesives in ophthalmology: history and current trends.
Guhan, Samantha; Peng, Si-Liang; Janbatian, Hrag; Saadeh, Stephanie; Greenstein, Stephen; Al Bahrani, Faisal; Fadlallah, Ali; Yeh, Tsai-Chu; Melki, Samir A
2018-03-26
Tissue adhesives are gaining popularity in ophthalmology, as they could potentially reduce the complications associated with current surgical methods. An ideal tissue adhesive should have superior tensile strength, be non-toxic and anti-inflammatory, improve efficiency and be cost-effective. Both synthetic and biological glues are available. The primary synthetic glues include cyanoacrylate and the recently introduced polyethylene glycol (PEG) derivatives, while most biological glues are composed of fibrin. Cyanoacrylate has a high tensile strength, but rapidly polymerises upon contact with any fluid and has been associated with histotoxicity. Fibrin induces less toxic and inflammatory reactions, and its polymerisation time can be controlled. Tensile strength studies have shown that fibrin is not as strong as cyanoacrylate. While more research is needed, PEG variants currently appear to have the most promise. These glues are non-toxic, strong and time-effective. Through MEDLINE and internet searches, this paper presents a systematic review of the current applications of surgical adhesives to corneal, glaucoma, retinal, cataract and strabismus surgeries. Our review suggests that surgical adhesives have promise to reduce problems in current ophthalmic surgical procedures. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
CO(2) Laser Fascia to Dura Soldering for Pig Dural Defect Reconstruction.
Forer, Boaz; Vasileyev, Tamar; Gil, Ziv; Brosh, Tamar; Kariv, Naam; Katzir, Abraham; Fliss, Dan M
2007-02-01
The purposes of this study were to demonstrate that laser soldering is safe and effective for tissue bonding in dural reconstruction and to compare this new reconstruction technique to an established one. A temperature-controlled fiberoptic CO(2) laser system or fibrin glue were used for in vitro dural defect reconstruction in two groups of pigs. The CO(2) laser technique was also used for dural reconstruction in live pigs. The burst pressure of the reconstructed dura by the laser system was significantly higher than that of fibrin glue (mean pressure 258.5 +/- 117.3 cm H(2)O and 76.8 +/- 47.2 cm H(2)O, respectively). There were no postoperative complications and no signs of thermal damage to the dura, fascia, or underlying tissue on histological analysis following the in vivo CO(2) laser experiments. Temperature-controlled laser soldering is an effective technique for dural repair. It creates a strong tissue bonding with no thermal damage to the tissue. The burst pressure of the reconstructed dura done with laser soldering is significantly higher than that of fibrin glue.
Ishii, Keiichi; Kawashima, Hideki; Hayama, Takuma; Mayabashira, Sumika; Oka, Shiro; Sugimoto, Toshikado
2011-11-01
Various hemostatic agents have been used quite effectively for hemostasis, as well as for providing effective adhesion during laparoscopic partial nephrectomies. In this study, we investigated the adhesiveness to the renal tissue of some sheet-type hemostatic agents used in combination with a liquid fibrin sealant. In Experiment A, component solutions of the fibrin glue (liquid fibrin sealant) were dripped onto a kite string placed annularly on a porcine kidney slice. Then, one of the sheet-type hemostats--namely, the collagen, gelatin, or cellulose hemostat--was placed on the slices, and a string scale was used to measure the force needed to pull the string apart vertically from the kidney slice. Twelve slices were used for each group, and the weight data were analyzed statistically. The tissue adhering to each sheet-type hemostatic agent was fixed in formalin and sliced and then examined by light microscopy after hematoxylin and eosin staining. In Experiment B, the solutions were dripped onto the sheet-type hemostatic agent placed first on the slice, and the force needed for pulling apart the hemostat sheet from the slice was similarly examined. The combination of fibrin glue plus a collagen hemostat was clearly superior in Experiment A, but the hemostat and renal tissue could be pulled apart more easily in Experiment B. These results showed that fibrin glue could not exert its expected adhesive effect unless it is used in combination with another hemostatic agent or is directly applied to renal tissue. It is important to obtain further comparative data among agents and select the appropriate agents, taking into consideration the type of surgery.
Effects of fibrinogen concentration on fibrin glue and bone powder scaffolds in bone regeneration.
Kim, Beom-Su; Sung, Hark-Mo; You, Hyung-Keun; Lee, Jun
2014-10-01
Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 80 mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6 ± 3.6%, while the compressive strength increased 1.16 ± 0.02 Mpa, when compared with the values for the 10 mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Rejoining of cut wounds by engineered gelatin-keratin glue.
Thirupathi Kumara Raja, S; Thiruselvi, T; Sailakshmi, G; Ganesh, S; Gnanamani, A
2013-08-01
Rejoining of cut tissue ends of a critical site challenges clinicians. The toxicity, antigenicity, low adhesive strength, flexibility, swelling and cost of the currently employed glue demands an alternative. Engineered gelatin-keratin glue (EGK-glue) described in the present study was found to be suitable for wet tissue approximation. EGK-glue was prepared by engineering gelatin with caffeic acid using EDC and conjugating with keratin by periodate oxidation. UV-visible, (1)H NMR and circular dichroism analyses followed by experiments on gelation time, rheology, gel adhesive strength (in vitro), wet tissue approximation (in vivo), H&E staining of tissue sections at scheduled time intervals and tensile strength of the healed skin were carried out to assess the effectiveness of the EGK-glue in comparison with fibrin glue and cyanoacrylate. Results of UV-visible, NMR and CD analyses confirmed the functionalization and secondary structural changes. Increasing concentration of keratin reduces the gelation time (<15s). Lap-shear test demonstrates the maximum adhesive strength of 16.6±1.2kPa. Results of hemocompatibility and cytocompatibility studies suggested the suitability of the glue for clinical applications. Tissue approximation property assessed using the incision wound model (Wistar strain) in comparison with cyanoacrylate and fibrin glue suggested, that EGK-glue explicitly accelerates the rejoining of tissue with a 1.86 fold increase in skin tensile strength after healing. Imparting quinone moiety to gelatin-keratin conjugates through caffeic acid and a weaker oxidizing agent provides an adhesive glue with appreciable strength, and hemocompatible, cytocompatible and biodegradable properties, which, rejoin the cut tissue ends effectively. EGK-glue obtained in the present study finds wide biomedical/clinical applications. Copyright © 2013 Elsevier B.V. All rights reserved.
Sitter, Helmut; Lorenz, Wilfried; Nicolay, Uwe; Krack, Walter; Hellenbrandt, Armin; Zielke, Andreas; Gajek, Hartwig; Ledertheil, Gertrud
2003-03-01
A previous upper-gastrointestinal bleeding trial showed that patients treated with repeated fibrin glue injection for upper-gastrointestinal bleeding have significantly less rebleeding than those treated with polidocanol. To analyse the cost and effectiveness of repeated fibrin glue injection and to investigate whether these results change physicians' attitudes. A retrospective random sample of five hospitals from the previous study, collection of cost identification, and follow-up data on 320 patients (155 in the polidocanol group, 165 in the fibrin glue group). An incremental cost-effectiveness analysis and comparison of outcomes was performed using chi-squared tests and Kaplan-Meier survival analysis. A survey was carried out using a questionnaire in the five hospitals on local guidelines for management of ulcer bleeding, and its results were analysed qualitatively. The measure of effectiveness is the number of prevented rebleedings. Further variables were length of hospital stay and length of intensive care unit (ICU) stay. The cost for the prevention of one additional rebleeding by repeated fibrin glue treatment amounts to 14,316 +/- 4981 euros (incremental cost-effectiveness ratio). There were no significant differences in length of stays in ICU or in hospital. The physicians did not change their management plans for patients with upper-gastrointestinal bleeding. In a survey, it was seen that other factors, such as local guidelines, attitudes towards new treatment options, and ease of handling of drugs, are more important than a result of a single study for a behavioural change of the doctors. The study was not designed prospectively to address a pharmacoeconomic question. As relevant variables (e.g. length of ICU stay) could not be reliably ascertained retrospectively, this may lead to biased estimates of the incremental cost-effectiveness ratio.
Effects of a Fibrin Sealant on Skin Graft Tissue Adhesion in a Rodent Model.
Balceniuk, Mark D; Wingate, Nicholas A; Krein, Howard; Curry, Joseph; Cognetti, David; Heffelfiner, Ryan; Luginbuhl, Adam
2016-07-01
To establish a rodent model for skin grafting with fibrin glue and examine the effects of fibrin glue on the adhesive strength of skin grafts without bolsters. Animal cohort. Academic hospital laboratory. Three skin grafts were created using a pneumatic microtome on the dorsum of 12 rats. Rats were evenly divided into experimental (n = 6) and control (n = 6) groups. The experimental group received a thin layer of fibrin glue between the graft and wound bed, and the control group was secured with standard bolsters. Adherence strength of the skin graft was tested by measurement of force required to sheer the graft from the recipient wound. Adhesion strength measurements were taken on postoperative days (PODs) 1, 2, and 3. The experimental group required an average force of 719 g on POD1, 895 g on POD2, and 676 g on POD3, while the average force in the control group was 161 g on POD1, 257 g on POD2, and 267 g on POD3. On each of the 3 PODs, there was a significant difference in adherence strength between the experimental and control groups (P = .036, P = .029, P = .024). There is a significant difference in the adhesion strength of skin grafts to the wound bed in the early postoperative period of the 2 groups. In areas of high mobility, using the fibrin sealant can keep the graft immobile during the critical phases of early healing. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.
A Biological Tissue Adhesive and Dissolvent System for Intraocular Tumor Plaque Brachytherapy.
Zloto, Ofira; Vishnevskia-Dai, Vicktoria; Moisseiev, Joseph; Belkin, Michael; Fabian, Ido Didi
2016-02-01
To examine a novel technique for simplified placement and removal of plaque brachytherapy by fibrin glue and urokinase (medac Gmbh, Hamburg, Germany). In six enucleated porcine eyes, plaques were placed on the episclera and fibrin glue was applied to cover it. Urokinase was used to dissolve the glue in three eyes and saline was used in three eyes. Adhesion strength was measured further on 15 plaques affixed to porcine eyes (glued in five with intact conjunctiva, glued in five with removed conjunctiva, and sutured in five). Saline had no effect on the glue-plaque-eye complex, whereas the urokinase (0.38 mL ± 0.08 mL) easily dissolved the adhesion between the glue layer and surrounding tissues. The weight required to detach the plaques was 0.349 kg ± 0.173 kg for glued eyes with intact conjunctiva, 0.405 kg ± 0.083 kg for sutured eyes (P = .59), and 0.032 kg ± 0.004 kg for glued eyes without intact conjunctiva (P ≤ .015). The usage of the biological adhesive and dissolvent system was applicable for plaque surgery in an ex vivo animal model. Copyright 2016, SLACK Incorporated.
A review of fibrin and fibrin composites for bone tissue engineering
Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J
2017-01-01
Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications. PMID:28761338
A review of fibrin and fibrin composites for bone tissue engineering.
Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J
2017-01-01
Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.
Rapidly photo-cross-linkable chitosan hydrogel for peripheral neurosurgeries.
Rickett, Todd A; Amoozgar, Zohreh; Tuchek, Chad A; Park, Joonyoung; Yeo, Yoon; Shi, Riyi
2011-01-10
Restoring continuity to severed peripheral nerves is crucial to regeneration and enables functional recovery. However, the two most common agents for coaptation, sutures and fibrin glues, have drawbacks such as inflammation, pathogenesis, and dehiscence. Chitosan-based adhesives are a promising alternative, reported to have good cytocompatibility and favorable immunogenicity. A photo-cross-linkable hydrogel based on chitosan is proposed as a new adhesive for peripheral nerve anastomosis. Two Az-chitosans were synthesized by conjugating 4-azidobenzoic acid with low (LMW, 15 kDa) and high (HMW, 50-190 kDa) molecular weight chitosans. These solutions formed a hydrogel in less than 1 min under UV light. The LMW Az-chitosan was more tightly cross-linked than the HMW variant, undergoing significantly less swelling and possessing a higher rheological storage modulus, and both Az-chitosan gels were stiffer than commercial fibrin glue. Severed nerves repaired by Az-chitosan adhesives tolerated longitudinal forces comparable or superior to fibrin glue. Adhesive exposure to intact nerves and neural cell culture showed both Az-chitosans to be nontoxic in the acute (minutes) and chronic (days) time frames. These results demonstrate that Az-chitosan hydrogels are cytocompatible and mechanically suitable for use as bioadhesives in peripheral neurosurgeries.
Mohan, Sujatha; John, Bina; Rajan, Mohan; Malkani, Harsha; Nagalekshmi, S V; Singh, Siddhartha
2017-06-01
The aim of this study is to analyze the postoperative visual outcomes of fibrin glue-assisted, suture-less posterior chamber (PC) intraocular lens (IOL) implantation technique in eyes with inadequate capsule support at a tertiary eye care hospital in South India. This is a retrospective, nonrandomized case series. This study analyzes 94 eyes which underwent PC-IOL implantation by fibrin glue-assisted, suture-less technique. All patients who had IOL implants by the fibrin glue-assisted PC-IOL technique from August 2009 to January 2014 were included in the study. Intra- and post-operative complications were analyzed. The postoperative best spectacle-corrected visual acuity (BSCVA) was evaluated and recorded at the end of 6 months. The data were analyzed using SPSS version 16.1 (SPSS Inc., Chicago, Illinois, USA) using two sample paired t-test and independent t-test. A total of 94 eyes of 92 patients that underwent glued IOL implantation over a period of 5 years were analyzed. Out of 94 eyes, 77 eyes (84.6%) maintained or improved on their preoperative BSCVA (P = 0.012). We conclude that glued IOL implantation is a feasible option in rehabilitating patients with aphakia without adequate capsular support.
Superimposed Fungal Ulcer after Fibrin Glue Sealant in Infectious Corneal Ulcer
Byun, Yong-Soo
2011-01-01
A healthy 27-year-old woman with a corneal ulcer underwent fibrin gluing with a bandage contact lens twice, due to an impending perforation. The ulcer lesion slowly progressed, unresponsive to topical antibiotics and amphotericin B. We removed the gluing patch and performed a corneal or scraping or biopsy with multiple amniotic membrane grafts to seal the thinned or perforated cornea. Three days after the surgery, the corneal cultures grew Fusarium, as well as Enterococcus faecalis. Three weeks after surgery, the outermost layer of amniotic membranes, serving as a temporary patch, was removed. The anterior chamber was clear without cells. The signs of infection clinically and symptomatically cleared up four weeks later. Two months after surgery, the lesion became enhanced by amniotic membranes. The use of fibrin glue in infectious keratitis should be avoided, because it not only masks the underlying lesion, but it also interferes with drug penetration into the underlying lesion. PMID:22131784
Hwang, Ho Sik; Cho, Kyong Jin; Rand, Gabriel; Chuck, Roy S; Kwon, Ji Won
2018-06-07
In our study we describe a method that optimizes size of excision and autografting for primary pterygia along with the use of intraoperative MMC and fibrin glue. Our objective is to propose a simple, optimizedpterygium surgical technique with excellent aesthetic outcomes and low rates of recurrence and otheradverse events. Retrospective chart review of 78 consecutive patients with stage III primary pterygia who underwent an optimal excision technique by three experienced surgeons. The technique consisted of removal of the pterygium head, excision of the pterygium body and Tenon's layer limited in proportion to the length of the head, application of intraoperative mitomycin C to the defect, harvest of superior bulbar limbal conjunctival graft, adherence of graft with fibrin glue. Outcomes included operative time, follow up period, pterygium recurrence, occurrences of incorrectly sized grafts, and other complications. All patients were followed up for more than a year. Of the 78 patients, there were 2 cases of pterygium recurrence (2.6%). There was one case of wound dehiscence secondary to small-sized donor conjunctivaand one case of over-sized donor conjunctiva, neither of which required surgical correction. There were no toxic complications associated with the use of mitomycin C. Correlating the excision of the pterygium body and underlying Tenon's layer to the length of the pterygium head, along with the use intraoperative mitomycin C, limbal conjunctival autografting, and fibrin adhesionresulted in excellent outcomes with a low rate of recurrence for primary pterygia.
Rieder, Erwin; Stoiber, Martin; Scheikl, Verena; Poglitsch, Marcus; Dal Borgo, Andrea; Prager, Gerhard; Schima, Heinrich
2011-01-01
Laparoscopic ventral hernia repair has gained popularity among minimally invasive surgeons. However, mesh fixation remains a matter of discussion. This study was designed to compare noninvasive fibrin-glue attachment with tack fixation of meshes developed primarily for intra-abdominal use. It was hypothesized that particular mesh structures would substantially influence detachment force. For initial evaluation, specimens of laminated polypropylene/polydioxanone meshes were anchored to porcine abdominal walls by either helical titanium tacks or absorbable tacks in vitro. A universal tensile-testing machine was used to measure tangential detachment forces (TF). For subsequent experiments of glue fixation, polypropylene/polydioxanone mesh and 4 additional meshes with diverse particular mesh structure, ie, polyvinylidene fluoride/polypropylene mesh, a titanium-coated polypropylene mesh, a polyester mesh bonded with a resorbable collagen, and a macroporous condensed PTFE mesh were evaluated. TF tests revealed that fibrin-glue attachment was not substantially different from that achieved with absorbable tacks (median TF 7.8 Newton [N], range 1.3 to 15.8 N), but only when certain open porous meshes (polyvinylidene fluoride/polypropylene mesh: median 6.2 N, range 3.4 to 10.3 N; titanium-coated polypropylene mesh: median 5.2 N, range 2.1 to 11.7 N) were used. Meshes coated by an anti-adhesive barrier (polypropylene/polydioxanone mesh: median 3.1 N, range 1.7 to 5.8 N; polyester mesh bonded with a resorbable collagen: median 1.3 N, range 0.5 to 1.9 N), or the condensed PTFE mesh (median 3.1 N, range 2.1 to 7.0 N) provided a significantly lower TF (p < 0.01). Fibrin glue appears to be an appealing noninvasive option for mesh fixation in laparoscopic ventral hernia repair, but only if appropriate meshes are used. Glue can also serve as an adjunct to mechanical fixation to reduce the number of invasive tacks. Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Stretching single fibrin fibers hampers their lysis.
Li, Wei; Lucioni, Tomas; Li, Rongzhong; Bonin, Keith; Cho, Samuel S; Guthold, Martin
2017-09-15
Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis. Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis. Fibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has a similar effect on reducing lysis as crosslinking fibers. At the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Mehanna, Radwa A.; Nabil, Iman; Attia, Noha; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Elsayed, Fatma
2015-01-01
Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740
Shinya, Noriko; Oka, Shirou; Miyabashira, Sumika; Kaetsu, Hiroshi; Uchida, Takanori; Sueyoshi, Masuo; Takase, Kozo; Akuzawa, Masao; Miyamoto, Atsushi; Shigaki, Takamichi
2009-01-01
Although fibrin sealant (FS) has an advantage of high biocompatibility, its adhesive force and sealing effect have been generally considered to be inadequate. In the present study, a high adhesive force and sealing effect were obtained by first rubbing fibrinogen solution into the target tissue, attaching polyglycolic acid (PGA) felt to the treated area, and finally spraying it with FS. This method was compared with three conventional FS application methods and a method using fibrin glue-coated collagen fleece. The adhesive force resulting from the present method was 12 times higher than that for the sequential application method, 4.5 times higher than the spray method, 2.5 times higher than the rubbing and spray method, and 2.2 times higher than the use of fibrin glue-coated collagen fleece. The high adhesive force of FS with PGA felt seemed to be due the high fibrin content of the fibrin gel (FG). Light and electron microscopic observations suggested that the formation of FG in closer contact with the muscle fibers was a factor contributing to this superior adhesive force. Comparison of the sealing effect of the present method with other methods using various biomaterials in combination with FS showed that the sealing effect of FS with PGA felt was 1.4 times higher that of polyglactin 910, 1.8 times that of polytetrafluoroethylene, and 6.7 times that of oxidized regenerated cellulose.
Ono, K; Ishihara, M; Ozeki, Y; Deguchi, H; Sato, M; Saito, Y; Yura, H; Sato, M; Kikuchi, M; Kurita, A; Maehara, T
2001-11-01
In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.
Traumatic dislocation of the incudostapedial joint repaired with fibrin tissue adhesive.
Nikolaidis, Vasilios
2011-03-01
We present a case of traumatic dislocation of the incudostapedial joint (ISJ) and a simple method for controlled application of the glue using commercial fibrin tissue adhesive. A 26-year-old female presented to our ENT clinic for hearing impairment to her left ear 2 months after a head trauma due to a motorcycle accident. The audiogram revealed a 40- to 50-dB HL conductive hearing loss with a notch configuration in bone conduction curve on the left ear. Computed tomography of the left temporal bone revealed a longitudinal fracture line. An exploratory tympanotomy was performed under general anesthesia. The ISJ was found dislocated while the incus was trapped by the edges of the bony lateral attic wall fracture. A small bony edge that impeded incus movement was removed and a small amount of the glue was precisely applied to the lenticular process of the incus with an angled incision knife. The long process of the incus was firmly pressed over the stapes for 30 seconds with a 90° hook and 60 seconds after the application of the glue the ISJ was repaired. One year after our patient achieved full airbone gap (ABG) closure (ABG, ≤10 dB HL), while she demonstrated overclosure in frequencies 2 and 4 kHz. Fibrin tissue glue allowed safe, rapid, and accurate repair of the ISJ and resulted in an anatomically normal articulation as the mass and shape of the ossicles was preserved. Moreover, our patient achieved full ABG closure. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Reduction of the closure time of postoperative enterocutaneous fistulas with fibrin sealant.
Avalos-González, Jorge; Portilla-deBuen, Eliseo; Leal-Cortés, Caridad Aurea; Orozco-Mosqueda, Abel; Estrada-Aguilar, María del Carmen; Velázquez-Ramírez, Gabriela Abigail; Ambriz-González, Gabriela; Fuentes-Orozco, Clotilde; Guzmán-Gurrola, Aldo Emmerson; González-Ojeda, Alejandro
2010-06-14
To assess whether the use of fibrin sealant shortens the closure time of postoperative enterocutaneous fistulas (ECFs). The prospective case-control study included 70 patients with postoperative ECFs with an output of < 500 mL/d, a fistulous tract of > 2 cm and without any local complication. They were divided into study (n = 23) and control groups (n = 47). Esophageal, gastric and colocutaneous fistulas were monitored under endoscopic visualization, which also allowed fibrin glue application directly through the external hole. Outcome variables included closure time, time to resume oral feeding and morbidity related to nutritional support. There were no differences in mean age, fistula output, and follow-up. Closure-time for all patients of the study group was 12.5 +/- 14.2 d and 32.5 +/- 17.9 d for the control group (P < 0.001), and morbidity related to nutritional support was 8.6% and 42.5%, respectively (P < 0.01). In patients with colonic fistulas, complete closure occurred 23.5 +/- 19.5 d after the first application of fibrin glue, and spontaneous closure was observed after 36.2 +/- 22.8 d in the control group (P = 0.36). Recurrences were observed in 2 patients because of residual disease. One patient of each group died during follow-up as a consequence of septic complications related to parenteral nutrition. Closure time was significantly reduced with the use of fibrin sealant, and oral feeding was resumed faster. We suggest the use of fibrin sealant for the management of stable enterocutaneous fistulas.
Koc, Baris B; Somorjai, Nicolaas; P M Kiesouw, Egid; Vanderdood, Kurt; Meesters-Caberg, Marleen; Draijer, Frits W; Jansen, Edwin J P
2017-01-01
A Morel-Lavallée lesion is a post-traumatic closed degloving injury of soft tissue. The lesion is due to a shearing trauma with separation of subcutaneous tissue from underlying fascia. When conservative treatment fails, surgical treatment is imperative. Commonly, open drainage and debridement is performed. This case report describes a Morel-Lavallée lesion of the knee in a professional soccer player who was successfully treated with endoscopic debridement and fibrin glue injection after failure of conservative management. This method achieves the goal of an open surgical debridement without exposing patients to an increased morbidity. Copyright © 2016. Published by Elsevier B.V.
Hypersensitivity to sub-Tenon's topotecan in fibrin adhesive in patients with retinoblastoma.
Astudillo, Paulita Pamela P; Durairaj, Priya; Chan, Helen S L; Héon, Elise; Gallie, Brenda L
2015-02-01
Sub-Tenon's space delivery of topotecan in a fibrin sealant was used as an adjunct to laser therapy for small retinoblastoma tumors in 25 children (77 injections). We report serious hypersensitivity reactions in 2 children on their third sub-Tenon's injection of topotecan in fibrin sealant. One child subsequently had topotecan in an autologous blood clot with no allergic reaction. Although allergic reaction to topotecan has been reported in the literature, fibrin glue reactions are more common and are likely due to aprotinin hypersensitivity. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Barbizan, Roberta; Seabra Ferreira, Rui
2016-01-01
Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4–L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity, 4 and 12 weeks after lesion. Sciatic nerves were processed to investigate Schwann cell activity by p75NTR expression (4 weeks after surgery) and to count myelinated axons and morphometric evaluation (12 weeks after surgery). Walking track test was used to evaluate gait recovery, up to 12 weeks. The results indicate that both fibrin sealants are similarly efficient. However, the snake-derived fibrin glue is a potentially safer alternative for being a biological and biodegradable product which does not contain human blood derivatives. Therefore, the venom glue can be a useful tool for the scientific community due to its advantages and variety of applications. PMID:27642524
Photocrosslinkable chitosan as a biological adhesive.
Ono, K; Saito, Y; Yura, H; Ishikawa, K; Kurita, A; Akaike, T; Ishihara, M
2000-02-01
A photocrosslinkable chitosan to which both azide and lactose moieties were introduced (Az-CH-LA) was prepared as a biological adhesive for soft tissues and its effectiveness was compared with that of fibrin glue. Introduction of the lactose moieties resulted in a much more water-soluble chitosan at neutral pH. Application of ultraviolet light (UV) irradiation to photocrosslinkable Az-CH-LA produced an insoluble hydrogel within 60 s. This hydrogel firmly adhered two pieces of sliced ham with each other, depending upon the Az-CH-LA concentration. The binding strength of the chitosan hydrogel prepared from 30-50 mg/mL of Az-CH-LA was similar to that of fibrin glue. Compared to the fibrin glue, the chitosan hydrogel more effectively sealed air leakage from pinholes on isolated small intestine and aorta and from incisions on isolated trachea. Neither Az-CH-LA nor its hydrogel showed any cytotoxicity in cell culture tests of human skin fibroblasts, coronary endothelial cells, and smooth muscle cells. Furthermore, all mice studied survived for at least 1 month after implantation of 200 microL of photocrosslinked chitosan gel and intraperitoneal administration of up to 1 mL of 30 mg/mL of Az-CH-LA solution. These results suggest that the photocrosslinkable chitosan developed here has the potential of serving as a new tissue adhesive in medical use. Copyright 2000 John Wiley & Sons, Inc.
Izumi, Yotaro; Kawamura, Masafumi; Gika, Masatoshi; Nomori, Hiroaki
2010-03-01
The aim of this study was to compare the morphology of the bronchial stump after lobectomy between mechanical stapler closure and manual suture closure. The effect of fibrin glue application on each method of closure was also observed. Right upper lobectomy was performed in beagles (n=31) using staplers (ST group) or sutures (SU group). In a separate experiment, fibrin glue was sprayed onto the stump after each respective method of closure. After one week, the stump region was examined macroscopically, and also by histology. chi(2)-Test and Mann-Whitney test were used for comparative analysis. The incidence of adhesion formation between the surrounding tissues was significantly reduced in the ST group in comparison to the SU group (22 vs. 80%, P=0.04). The thickness of granulation tissue over the stump was significantly reduced in the ST group in comparison to the SU group (0.8+/-0.2 vs. 2.5+/-0.3 mm, P<0.0001). Vessel density in the granulation tissue was also significantly reduced in the ST group in comparison to the SU group (6+/-2 vs. 16+/-2, P=0.003). Fibrin glue application after stapler closure significantly increased the incidence of adhesion formation, granulation tissue thickness, and vessel density in the granulation tissue over the stump.
Nakayama, Noriyuki; Yano, Hirohito; Egashira, Yusuke; Enomoto, Yukiko; Ohe, Naoyuki; Kanemura, Nobuhiro; Kitagawa, Junichi; Iwama, Toru
2018-01-01
Commercially available fibrin glue (Com-FG), which is used commonly worldwide, is produced with pooled human plasma from multiple donors. However, it has added bovine aprotinin, which involves the risk of infection, allogenic immunity, and allergic reactions. We evaluate the efficacy, reliability, and safety of completely autologous fibrin glue (CAFG). From August 2014 to February 2016, prospective data were collected and analyzed from 153 patients. CAFG was prepared with the CryoSeal System using autologous blood and was applied during neurosurgical procedures. Using CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets, we performed a pinpoint hemostasis, transposed the offending vessels in a microvascular decompression, and covered the dural incision to prevent cerebrospinal fluid leakage. The CryoSeal System had generated up to a mean of 4.51 mL (range, 3.0-8.4 mL) of CAFG from 400 mL autologous blood. Com-FG products were not used in our procedures. Only 6 patients required an additional allogeneic blood transfusion. The hemostatic effective rate was 96.1% (147 of 153 patients). Only 1 patient who received transsphenoidal surgery for a pituitary adenoma presented with the complication of delayed postoperative cerebrospinal fluid leakage (0.65%). No patient developed allergic reactions or systemic complications associated with the use of CAFG. CAFG effectively provides hemostatic, adhesive, and safety performance. The timing and three-dimensional shape of CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets solidification can be controlled with slow fibrin formation. The cost to prepare CAFG is similar compared with Com-FG products, and it can therefore be easily used at most institutions. Copyright © 2017 Elsevier Inc. All rights reserved.
Reduction of the closure time of postoperative enterocutaneous fistulas with fibrin sealant
Avalos-González, Jorge; Portilla-deBuen, Eliseo; Leal-Cortés, Caridad Aurea; Orozco-Mosqueda, Abel; del Carmen Estrada-Aguilar, María; Velázquez-Ramírez, Gabriela Abigail; Ambriz-González, Gabriela; Fuentes-Orozco, Clotilde; Guzmán-Gurrola, Aldo Emmerson; González-Ojeda, Alejandro
2010-01-01
AIM: To assess whether the use of fibrin sealant shortens the closure time of postoperative enterocutaneous fistulas (ECFs). METHODS: The prospective case-control study included 70 patients with postoperative ECFs with an output of < 500 mL/d, a fistulous tract of > 2 cm and without any local complication. They were divided into study (n = 23) and control groups (n = 47). Esophageal, gastric and colocutaneous fistulas were monitored under endoscopic visualization, which also allowed fibrin glue application directly through the external hole. Outcome variables included closure time, time to resume oral feeding and morbidity related to nutritional support. RESULTS: There were no differences in mean age, fistula output, and follow-up. Closure-time for all patients of the study group was 12.5 ± 14.2 d and 32.5 ± 17.9 d for the control group (P < 0.001), and morbidity related to nutritional support was 8.6% and 42.5%, respectively (P < 0.01). In patients with colonic fistulas, complete closure occurred 23.5 ± 19.5 d after the first application of fibrin glue, and spontaneous closure was observed after 36.2 ± 22.8 d in the control group (P = 0.36). Recurrences were observed in 2 patients because of residual disease. One patient of each group died during follow-up as a consequence of septic complications related to parenteral nutrition. CONCLUSION: Closure time was significantly reduced with the use of fibrin sealant, and oral feeding was resumed faster. We suggest the use of fibrin sealant for the management of stable enterocutaneous fistulas. PMID:20533600
A novel autologous scaffold for diced-cartilage grafts in dorsal augmentation rhinoplasty.
Bullocks, Jamal M; Echo, Anthony; Guerra, Gerardo; Stal, Samuel; Yuksel, Eser
2011-08-01
Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.
The influence of pterygium morphology on fibrin glue conjunctival autografting pterygium surgery.
Sandra, Sekelj; Zeljka, Janjetovic; Zeljka, Vukovic Arar; Kristian, Samardzic; Ivana, Aric
2014-02-01
To evaluate the influence of pterygium morphology on the efficacy and safety of fibrin glue in pterygium surgery with conjunctival autografting. A prospective case series. During a period of 15 months, 45 patients (51 eyes) were recruited from the General Hospital for pterygium surgery. Seven eyes (13.73 %) were operated on for a recurrent pterygium. Autologous conjunctiva was harvested from the superior bulbar conjunctiva and fixed with fibrin glue. The pterygia were preoperatively divided into atrophic/grade 1 (n = 18; 35.29 %), intermediate/grade 2 (n = 22; 43.14 %) or fleshy/grade 3 (n = 11; 21.57 %) according to clinical morphology. Patients were evaluated for intraoperative and postoperative complications and recurrence rates. The success rate was defined by no pterygium recurrences. Patients with 2-year follow-ups were included in this study. Fifty-one patients (21 females/30 males) with a mean age of 60-65 years (range 24-87 years) took part in the study. All patients completed the study. No intraoperative complications were noted. Postsurgical complications included graft edema (n = 4; 7.8 %), graft hyperemia (n = 2; 3.8 %), and graft dislocation (n = 3; 5.9 %); these complications were transient. One graft unfastened completely (2 %) and five pterygium recurrences occurred (n = 5; 9.8 %). The overall success rate was 90 % after 2 years. In grade I group there were no recurrences, in grade 2 group there were two recurrences, and in grade 3 group there were three recurrences. There were significantly more recurrences in grade 3 group than in grade 2 group. There were more recurrences in both groups than in group 1 (60 vs 40 vs 0 % of all recurrences, p ≤ 0.05). The use of fibrin glue is a safe, easy and effective technique for attaching the conjunctival autograft in pterygium surgery. The morphology of pterygium influences recurrence rates, without significance for intraoperative and postoperative complications.
Use of fibrin sealants in cardiovascular surgery: a systematic review.
Rousou, John A
2013-05-01
Fibrin sealants are used for hemostasis and tissue adherence. This systematic review summarizes published clinical data for fibrin sealant use in cardiovascular surgery. A literature search for the following terms was conducted using PubMed and EMBASE: (TISSEEL or Tissucol or Beriplast P or Evicel or Quixil or Crosseal or Reliseal or Fibringluraas or Bolheal or Tachosil or Vivostat or Vitagel or Artiss or "fibrin glue" or "fibrin sealant" or "fibrin tissue adhesive") and (cardiac or cardiovascular or vascular or heart or coronary or surgery). Case reports and series were excluded; although reports of controlled trials were preferred, uncontrolled trial data were also considered. Clinical trials and chart review analyses of fibrin sealants were identified and summarized. Although clinical trial data were available for other agents, the majority of published studies examined TISSEEL. Overall, TISSEEL and other fibrin sealants showed improvements over standard of care or control groups for a variety of predefined endpoints. Safety findings are also summarized. Data from these studies showed that fibrin sealants were well tolerated and provided effective hemostasis in a range of cardiac and aortic surgeries. © 2013 Wiley Periodicals, Inc.
Wu, Xiuwen; Ren, Jianan; Yuan, Yujie; Luan, Jianfeng; Yao, Genhong; Li, Jieshou
2013-01-01
Fibrin glue is a promising alternative for low-output enterocutaneous fistula closure. Bacterial flora colonizing inside the fistula tract, however, may limit the glue application. Single-donor-derived, platelet-rich materials were hypothesized in this study to have antimicrobial activity against Gram-negative microorganisms. Platelet-leukocyte fibrin (PLF), platelet-rich plasma (PRP), and platelet-poor plasma (PPP) were obtained from healthy volunteers. The amounts of platelet, leukocyte, and complement/antibody were determined. In vitro laboratory susceptibility to PLF and plasmas was determined by the Kirby-Bauer disc-diffusion method. Antimicrobial activity of PLF, PRP, and PPP against three Gram-negative ATCC strains was determined in a bacterial kill assay. Levels of complement and antibody did not significantly differ among PLF, PRP, and PPP (p > 0.05), while platelet and leukocyte counts in platelet-rich biomaterials were significantly higher than those in PPP (p < 0.001). The bactericidal effects produced by PLF and PRP were more pronounced than those by PPP in both qualitative and quantitative aspects. No inhibitory zones against three Gram-negative organisms were observed in the Bioseal®. In conclusion, our homemade PLF, as compared with commercial products, had remarkable antimicrobial activity against Gram-negative bacteria relevant to fistula colonization. The presence of platelets and leukocytes may play an important role in bacterial defense. This is the first study to demonstrate the antibacterial properties of single-unit PLF for fistula closure, presenting a new opportunity for glue sealing.
Rohm, Henning W; Lurtz, Claudia; Wegmann, Juergen; Odermatt, Erich K; Behrend, Detlef; Schmitz, Klaus-Peter; Sternberg, Katrin
2011-04-01
In body regions where damage and bleeding must be avoided, a substitute for mechanical tissue fixation by sutures or staplers is needed. Since tissue adhesives provide easy and fast handling they are a promising alternative. The present study reports the development and analysis of a tissue adhesive that consists of two adhesive components: hexamethylene diisocyanate (HDI) functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO) and chitosan chloride. This composition was chosen based on preliminary studies on several chain elongation agents. The present study evaluates this adhesive system by IR-spectroscopy, tensile tests, and gel point measurements in comparison to fibrin glue. The system's in vitro biocompatibility was tested with mouse fibroblasts (L929) according to ISO 10993-5. Furthermore, an implantation study was performed in SPF-Wistar rats. The adhesive strength of manually applied mixtures or mixtures applied by double chamber syringes with a mixing extruder was determined to be significantly higher than that of fibrin glue on bovine muscle tissue at 37°C. Tensile strength increased further when exposure time of the adhesive was increased from 10 min to 48 h. The rheological gel point determination showed that the mixture of ELA-NCO/DMSO and chitosan chloride offers a time window large enough to readjust the fused joint during surgery, as opposed to fibrin glue. Additionally, the in vitro and in vivo biocompatibility studies of the adhesive system revealed no toxic effects on the surrounding tissue. Copyright © 2010 Wiley Periodicals, Inc.
Hardten, David R; Fahmy, Mona M; Vora, Gargi K; Berdahl, John P; Kim, Terry
2015-07-01
To describe the long-term results of fibrin adhesive use in the management of epithelial ingrowth after laser in situ keratomileusis (LASIK). Private practice, Minneapolis, Minnesota, and an academic medical center, Durham, North Carolina, USA. Retrospective case series. Patients with a history of LASIK had epithelial ingrowth removal with mechanical debridement and fibrin glue application. Visual outcomes and the presence or absence of epithelial ingrowth were evaluated again after 3 months and at the last follow-up. The main outcome measures were recurrence of epithelial ingrowth and visual acuity. Thirty-nine eyes of 38 patients were evaluated. After epithelial ingrowth removal and application of fibrin glue, 31 eyes (79.5%) had no recurrence of ingrowth at the final follow-up and 5 eyes (12.8%) had mild epithelial ingrowth not requiring removal. Three eyes (7.7%) had significant epithelial ingrowth at the 3-month follow-up that required subsequent removal and fibrin application. At the 3-month follow-up visit, 76.9% of eyes achieved 20/25 or better corrected distance visual acuity (CDVA) and 69.2% of eyes achieved 20/40 or better uncorrected distance visual acuity (UDVA). At the last follow-up visit (mean 26.6 ± 17.0 months [SD]), 84.6% of eyes had 20/25 or better CDVA and 74.4% of eyes had 20/40 or better UDVA. Fibrin adhesive in conjunction with manual epithelial removal prevented a clinically significant recurrence of epithelial ingrowth in the majority of eyes. Larger randomized studies are needed to compare the success of this technique with that of others. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Hashemi, Hassan; Dadgostar, Alhan
2011-06-01
To assess the visual outcome of using fibrin adhesive in automated lamellar therapeutic keratoplasty with a microkeratome in the treatment of anterior corneal opacities. In this prospective noncomparative clinical trial, surgery was done on 10 eyes belonging to 9 patients with anterior stromal opacity (macular dystrophy, spheroidal degeneration, scarring because of advanced recurrent pterygium, refractive surgery, or trauma). Depending on the depth of the opacity, a 130- or 250-μm flap was removed from the recipient cornea using a microkeratome. Then, a thin layer of fibrin adhesive was spread over the bed, and a lenticule with the same thickness, created from the donor cornea, was positioned in place. After allowing the glue to set for about 5 minutes, a bandage contact lens was placed over the cornea, which was removed 7-10 days postoperatively. All corneas healed properly, and none required suturing or reoperation. During the follow-up period, no inflammation or rejection was observed. The donor cornea and the donor-recipient interface remained clear in all cases. The mean of best contact lens-corrected visual acuity improved from 1.14 ± 0.53 to 0.51 ± 0.23 in the logarithm of the minimum angle of resolution scale. The fibrin glue can provide safe and effective attachment needed in automated lamellar therapeutic keratectomy and obviates the need for suturing. However, it requires improvement for easier and safer use in ophthalmology.
[Fibrin glue for operative correction of septal deviations].
Boenisch, M; Nolst Trenité, G J
2004-11-01
The routine procedure after correction of septal deviations is the utilization of endonasal packing in order to avoid septal haematoma. However, the mechanical pressure of this packing damages the mucociliar activity of the mucosa and causes lymphoedema by blocking the lymphatic vessels. Besides it represents a foreign body within the nose causing pain and unpleasant feeling for the patient. In order to avoid these disadvantages, in 57 patients we used fibrin glue instead of nasal packing. After correction of the septal deviation the two mucoperichondrium blades where fixed together with Tissucol Duo Quick. This technique not only leads to haemostasis, but also provides fixation of the newly modeled septum. In only one patient we found a small unilateral septal haematoma, in all other cases the postoperative period showed no complications. Patients had a significant reduction of endonasal crusts and postoperative swelling. Patients comfort increased significant without the (standard) nasal packing.
Cappabianca, P; Cavallo, L M; Mariniello, G; de Divitiis, O; Romero, A D; de Divitiis, E
2001-08-01
To describe a simple method of sellar reconstruction after endoscopic endonasal transsphenoidal surgery that will allow rapid watertight closure of the sellar floor. A bent sheet of a polyester-silicone dural substitute, fashioned for this purpose with scissors, is introduced into the sella after removal of the lesion. Because of the consistency of the sheet, it opens spontaneously and becomes stuck. Autologous fat tissue or gelatin foam is positioned thereafter, followed by another layer of the dural substitute; a film of fibrin glue completes the sealing. Fifteen patients underwent this method and no postoperative cerebrospinal leak or other complication was experienced. This easy method of sellar reconstruction represents an effective and fast possibility to perform the final step of the endoscopic transsphenoidal procedure, which otherwise may cause maneuverability problems in the limited space of one nostril.
Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine.
Wu, Xiuwen; Ren, Jianan; Li, Jieshou
2012-05-01
The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.
Trudzinski, F C; Rädle, J; Treiber, G; Kramm, T; Sybrecht, G W
2008-11-01
A 53-year-old man was admitted because of anuria, dyspnea and a septic temperature. The patients' history included chronic alcoholism, chronic pancreatitis, COPD and a right nephrectomy because of nephrolithiasis. Urosepsis was initially suspected. The patients' clinical condition and nutritional state were severely reduced. Laboratory findings revealed severe systemic inflammation (leucocyte count: 22.4/nl, CRP: 324 mg/l). Computed tomography showed a large left-sided pleural effusion, encapsulated abdominal fluid below the diaphragm and alongside the pancreatic tail. After aspiration of the pleural effusion the diagnosis of an exsudate with elevated concentration of lipase (56,000 U/l) was confirmed. Endoscopic ultrasound showed a 3-4 cm pseudocystic mass originating in the region of the pancreatic tail. The ERP depicted chronic pancreatitis with strictures and destruction of the pancreatic duct. Two fistulae were identified, one proximal to a ductal stricture in the pancreatic head and a second one in the pancreatic tail which corresponded to the reported pseudocyst. The patient was admitted to the ICU with symptoms of impending sepsis. The pleural effusion was treated with CT-guided chest drainage. The initial endoscopic attempt at stent closure of the fistula failed because it was possible to pass through the ductal stricture only with a thin hydrophilic wire and small-lumen catheter. However, injection of fibrin glue into the proximal pancreatic duct over a length of 2 cm obliterated the fistula and the pleural effusion was resolved. Pancreatic-pleural or pancreatic-mediastinal fistula is a rare complication of pancreatitis associated with unilateral pleural effusion. Combined internal endoscopic drainage and external chest drainage is the treatment of choice. After failure of routine endoscopic therapy, endoscopic closure of fistulas using fibrin glue might offer an alternative treatment strategy.
Zhang, C; Ding, X; Lu, Y; Hu, L; Hu, G
2017-08-01
The aim of this study was to elucidate the risk factors for cerebrospinal fluid (CSF) rhinorrhoea following transsphenoidal surgery and discuss its prevention and treatments. We retrospectively reviewed 474 consecutive cases of pituitary adenoma treated with 485 transsphenoidal surgical procedures from January 2008 to December 2011 in our department. We analysed the incidence of intra- and post-operative CSF leakage and outcomes of various repair strategies. Intra-operative CSF leakage was encountered in 85 cases (17.9%), and post-operative CSF rhinorrhoea in 13 cases (2.7%). Seven of the 13 patients with post-operative CSF rhinorrhoea did not experience intra-operative CSF leakage; three of these patients had adrenocorticotropic hormone-secreting adenomas. Of the remaining 6 patients with both intra- and post-operative CSF leakage, 2 were treated for giant invasive prolactinomas, and 2 had previously undergone transsphenoidal surgery. In eight patients, the leak was resolved by lumbar puncture, lumbar external drainage, resting in a semi-reclining position, or other conservative treatment. Two CSF leaks were repaired with gelatine foam and fibrin glue using a transsphenoidal approach, and two with autologous fat graft and sellar floor reconstruction using a transnasal endoscopic approach. After undergoing two transnasal endoscopic repairs, one patient with post-operative CSF rhinorrhoea was successfully treated by further lumbar subarachnoid drainage. In conclusion, procedures using gelatine foam, fibrin glue and autologous fat graft are common and effective techniques for the management of CSF rhinorrhoea after transsphenoidal surgery. When a CSF leak is detected during transsphenoidal surgery, thorough sellar reconstruction and long-term follow-up are necessary. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.
Berney, Christophe R; Descallar, Joseph
2016-10-01
Chronic pain is a common complication arising after conventional open herniorrhaphy and to a lesser extent postlaparoscopic inguinal hernia repairs as groin incision is avoided. Although published studies support elimination of mesh fixation during endoscopic procedures, the vast majority of surgeons will still recommend it by fear of encountering increased recurrence rates, if omitted. Regrettably, penetrating staple or tack fixation devices are the preferred methods to secure the mesh and cannot be applied at the level of the triangles of 'doom' and 'pain' where hernia tends to reoccur the most. This ongoing prospective cohort study aimed to confirm the safety and advantages of fibrin glue, as a substitute to staple mesh fixation during totally extraperitoneal (TEP) inguinal hernia repair. Over a 10-year period, 703 patients underwent 1000 elective TEP inguinal hernia repairs. Mesh fixation was achieved using exclusively fibrin sealant. Patients were reviewed at 2, 6 weeks and thereafter on an ad hoc basis if judged necessary until complete resolution of their symptoms. Quality of life (QoL) was assessed in a subgroup of 320 patients using the Carolina Comfort Scale (CCS). No conversion to open surgery was observed. There were three cases of major morbidities and no mortality. Three months after surgery, only seven patients (1 %) experienced chronic groin or testicular discomfort and none of them required prescription painkillers. When using the CCS, at 2 weeks 93.1 % of the patients were either satisfied or very satisfied with their outcome. This satisfaction index increased up to 99.2 % at 6 weeks post surgery. Finally, only eight hernia recurrences (1.1 %) were reported, of which five occurred during the first month of the study. Fibrin glue mesh fixation of inguinal hernia during TEP repair is extremely safe and reliable, with a very high satisfaction index for the patients and limited risk of developing chronic pain.
Berruyer, M; Amiral, J; Ffrench, P; Belleville, J; Bastien, O; Clerc, J; Kassir, A; Estanove, S; Dechavanne, M
1993-05-01
Brief case histories of three patients aged 58, 38, and 44 years are reported. All underwent cardiovascular operations. Subsequently hemostasis test abnormalities developed between the seventh and eighth postoperative days after exposure to bovine thrombin used with fibrin glue. These were characterized by an increased activated partial thromboplastin time (64 to 147 seconds), prothrombin time (19 to 24 seconds), bovine thrombin time (> 120 seconds) and a markedly reduced factor V level (< 10% in two patients and 16% in the third patient). A patient plasma dilution of 1 in 200 with a normal plasma pool was necessary to correct bovine thrombin time. No fast-acting or progressive inhibitor against factor V could be detected by coagulation tests, and fresh frozen plasma perfusion had no effect. Plasmapheresis was performed preventatively to avoid bleeding, and factor V levels stabilized at around 50% after two to four exchanges. Immunologic studies showed that the inhibitors were directed not only against bovine factors but also against human ones. Therefore factor V decrease could have been the result of rapid clearance from the circulation of complexes formed with a nonneutralizing inhibitor that is not detected by clotting tests. These antibodies were purified by standard methods and immunoaffinity. Fast immunization could be explained by a prior sensitization to bovine thrombin exposure during previous operations. It is suggested that bovine thrombin used with fibrin glue contains small amounts of factor V and may be responsible for these abnormalities. This is in agreement with previous literature reports. However, these described neutralizing factor V inhibitors, which were easily detected.
Efe, Turgay; Füglein, Alexander; Heyse, Thomas J; Stein, Thomas; Timmesfeld, Nina; Fuchs-Winkelmann, Susanne; Schmitt, Jan; Paletta, Jürgen R J; Schofer, Markus D
2012-02-01
Adequate graft fixation over a certain time period is necessary for successful cartilage repair and permanent integration of the graft into the surrounding tissue. The aim of the present study was to test the primary stability of a new cell-free collagen gel plug (CaReS(®)-1S) with two different graft fixation techniques over a simulated early postoperative period. Isolated chondral lesions (11 mm diameter by 6 mm deep) down to the subchondral bone plate were created on the medial femoral condyle in 40 porcine knee specimens. The collagen scaffolds were fixed in 20 knees each by press-fit only or by press-fit + fibrin glue. Each knee was then put through 2,000 cycles in an ex vivo continuous passive motion model. Before and after the 2,000 motions, standardized digital pictures of the grafts were taken. The area of worn surface as a percentage of the total collagen plug surface was evaluated using image analysis software. No total delamination of the scaffolds to leave an empty defect site was recorded in any of the knees. The two fixation techniques showed no significant difference in worn surface area after 2,000 cycles (P = n.s.). This study reveals that both the press-fit only and the press-fit + fibrin glue technique provide similar, adequate, stability of a type I collagen plug in the described porcine model. In the clinical setting, this fact may be particularly important for implantation of arthroscopic grafts.
Buchaim, Rogerio Leone; Andreo, Jesus Carlos; Barraviera, Benedito; Ferreira Junior, Rui Seabra; Buchaim, Daniela Vieira; Rosa Junior, Geraldo Marco; de Oliveira, Alexandre Leite Rodrigues; de Castro Rodrigues, Antonio
2015-04-01
The purpose of this study was to assess whether the adhesive permits the collateral repair of axons originating from a vagus nerve to the interior of a sural nerve graft, and whether low-level laser therapy (LLLT) assists in the regeneration process. Study sample consisted of 32 rats randomly separated into three groups: Control Group (CG; n=8), from which the intact sural nerve was collected; Experimental Group (EG; n=12), in which one of the ends of the sural nerve graft was coapted to the vagus nerve using the fibrin glue; and Experimental Group Laser (EGL; n=12), in which the animals underwent the same procedures as those in EG with the addition of LLLT. Ten weeks after surgery, the animals were euthanized. Morphological analysis by means of optical and electron microscopy, and morphometry of the regenerated fibers were employed to evaluate the results. Collateral regeneration of axons was observed from the vagus nerve to the interior of the autologous graft in EG and EGL, and in CG all dimensions measured were greater and presented a significant difference in relation to EG and EGL, except for the area and thickness of the myelin sheath, that showed significant difference only in relation to the EG. The present study demonstrated that the fibrin glue makes axonal regeneration feasible and is an efficient method to recover injured peripheral nerves, and the use of low-level laser therapy enhances nerve regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.
Fibrin gel as a scaffold for skin substitute – production and clinical experience.
Kljenak, Antun; Tominac Trcin, Mirna; Bujić, Marina; Dolenec, Tamara; Jevak, Martina; Mršić, Gordan; Zmiš, Gordana; Barčot, Zoran; Muljačić, Ante; Popović, Maja
2016-06-01
The purpose of this study was to create a fibrin-based human skin substitute in vitro with epidermal and dermal component and to assess its healing potential in deep partial and full thickness burns. Fibrin scaffolds were prepared from commercial fibrin glue kits. Human fibroblasts were cultured in fibrin gel. Human keratinocytes were seeded on the top of the gel. Viability of cells was determined fluorimetrically. Scanning electron microscope and immunocytochemistry analysis of cultured cells were performed. After hydrosurgical preparation of deep burn necrotic tissue, wound bed was prepared for skin substitutes. Progress of healing was documented using visual estimation and photos. Scanning electron microscope images showed good cell attachment and colony spreading of keratinocytes and fibroblasts on fibrin scaff old. Immunofluorescent staining of cell cultures on fibrin scaffold showed expression of vimentin, a marker of fibroblast cells, cytokeratin 19, a marker of epithelial stem cells, as well as involucrin, a marker of differentiated keratinocytes. Clinical results clearly showed that appearance of the skin did not differ significantly from the areas of transplanted skin using split-thickness skin graft techniques. In conclusion, using these fibrin-cultured autografts on massive full-thickness burn resulted in good healing.
Attar, Bijan Movahedian; Zalzali, Haidar; Razavi, Mohammad; Ghoreishian, Mehdi; Rezaei, Majid
2012-10-01
Epineural suturing is the most common technique used for peripheral nerve anastomosis. In addition to the foreign body reaction to the suture material, the surgical duration and difficulty of suturing in confined anatomic locations are major problems. We evaluated the effectiveness of fibrin glue as an acceptable alternative for nerve anastomosis in dogs. Eight adult female dogs weighing 18 to 24 kg were used in the present study. The facial nerve was transected bilaterally. On the right side, the facial nerve was subjected to epineural suturing; and on the left side, the nerve was anastomosed using fibrin adhesive. After 16 weeks, the nerve conduction velocity and proportion of the nerve fibers that crossed the anastomosis site were evaluated and compared for the epineural suture (right side) and fibrin glue (left side). The data were analyzed using the paired t test and univariate analysis of variance. The mean postoperative nerve conduction velocity was 29.87 ± 7.65 m/s and 26.75 ± 3.97 m/s on the right and left side, respectively. No statistically significant difference was found in the postoperative nerve conduction velocity between the 2 techniques (P = .444). The proportion of nerve fibers that crossed the anastomotic site was 71.25% ± 7.59% and 72.25% ± 8.31% on the right and left side, respectively. The histologic evaluation showed no statistically significant difference in the proportion of the nerve fibers that crossed the anastomotic site between the 2 techniques (P = .598). The results suggest that the efficacies of epineural suturing and fibrin gluing in peripheral nerve anastomosis are similar. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Albumen Glue, New Material for Conjunctival Graft Surgery, an Animal Experiment
NASA Astrophysics Data System (ADS)
Kartiwa, A.; Miraprahesti, R.; Sovani, I.; Enus, S.; Boediono, A.
2017-02-01
Attach conjunctival graft commonly used are suture technique and fibrin glue. This study was to investigate albumen glue as an alternative to suture technique in attaching conjunctival graft in rabbits. Aim of this study was to compare the conjunctival wound healing between albumen glue and suture technique in rabbit eye as a model. There was an experimental animal study included 32 eyes (16 rabbits) in PT. Bio Farma (Persero) and Histology Laboratory, Faculty of Medicine, Padjadjaran University from March 2014 to July 2104. The study consisted of albumen glue group and suture technique group. The examination included the comparison of conjunctival graft attachment and histologic examination by microscopically was done to obtain the wound gap, then analyze by Mann-Whitney test. The results indicated that the graft attachment was significantly better-using albumen glue (grade 4) compared to suture (grade 2-3) on day-1 after surgery (p=0,000). The wound gap was smaller using albumen glue (0-0,33 μm versus 5,33-14 μm ; p=0,0005) on 10 minutes after surgery and 0 μm versus 0,33-4 μm ; p=0,0005 on day-7 after surgery. In conclusion, the graft attachment using albumen glue was better and the wound gap was smaller using albumen glue than suture technique.
Zhu, Yuanzheng; Yi, Yangyan; Yang, Shuifa; Zhang, Jing; Wu, Shu; Wang, Zhaohui
2017-09-01
To discuss the possibility of constructing injectable tissue engineered adipose tissue, and to provide a new approach for repairing soft tissue defects. Human adipose-derived stem cells (hADSCs) were extracted from the lipid part of human liposuction aspirate by enzymatic digestion and identified by morphological observation, flow cytometry, and adipogenic induction. The hADSCs underwent transfection by lentivirus vector expressing hepatocyte growth factor and green fluorescent protein (HGF-GFP-LVs) of different multiplicity of infection (MOI, 10, 30, 50, and 100), the transfection efficiency was calculated to determine the optimum MOI. The hADSCs transfected by HGF-GFP-LVs of optimal MOI and being adipogenic inducted were combined with injectable fibrin glue scaffold, and were injected subcutaneously into the right side of the low back of 10 T-cell deficiency BALB/c female nude mice (transfected group); non-HGF-GFP-LVs transfected hADSCs (being adipogenic inducted) combined with injectable fibrin glue scaffold were injected subcutaneously into the left side of the low back (untransfected group); and injectable fibrin glue scaffold were injected subcutaneously into the middle part of the neck (blank control group); 0.4 mL at each point. Twelve weeks later the mice were killed and the implants were taken out. Gross observation, wet weight measurement, HE staining, GFP fluorescence labeling, and immunofluorescence staining were performed to assess the in vivo adipogenic ability of the seed cells and the neovascularization of the grafts. The cultured cells were identified as hADSCs. Poor transfection efficiency was observed in MOI of 10 and 30, the transfection efficiency of MOI of 50 and 100 was more than 80%, so the optimum MOI was 50. Adipose tissue-like new-born tissues were found in the injection sites of the transfected and untransfected groups after 12 weeks of injection, and no new-born tissues was found in the blank control group. The wet-weight of new-born tissue in the transfected group [(32.30±4.06) mg] was significantly heavier than that of the untransfected group [(25.27±3.94) mg] ( t =3.929, P =0.001). The mature adipose cells in the transfected group [(126.93±5.36) cells/field] were significantly more than that in the untransfected group [(71.36±4.52) cells/field] ( t =30.700, P =0.000). Under fluorescence microscopy, some of the single cell adipocytes showed a network of green fluorescence, indicating the presence of GFP labeled exogenous hADSCs in the tissue. The vascular density of new-born tissue of the transfected group [(16.37±2.76)/field] was significantly higher than that of the untransfected group [(9.13±1.68)/field] ( t =8.678, P =0.000). The hADSCs extracted from the lipid part after liposuction can be used as seed cells. After HGF-GFP-LVs transfection and adipose induction, the hADSCs combined with injectable fibrin glue scaffold can construct mature adipose tissue in vivo , which may stimulate angiogenesis, and improve retention rate of new-born tissue.
Kim, Beom Su; Shkembi, Feride; Lee, Jun
2017-01-01
Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10 -7 -10 -4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.
Kim, Beom Su; Shkembi, Feride
2017-01-01
Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration. PMID:28210623
Bindi, Marco; Rivelli, Matteo; Solej, Mario; Enrico, Stefano; Martino, Valter
2016-01-01
Abstract Laparoscopic transabdominal preperitoneal inguinal hernia repair is a safe and effective technique. In this study we tested the hypothesis that self-gripping mesh used with the laparoscopic approach is comparable to polypropylene mesh in terms of perioperative complications, against a lower overall cost of the procedure. We carried out a prospective randomized trial comparing a group of 30 patients who underwent laparoscopic inguinal hernia repair with self-gripping mesh versus a group of 30 patients who received polypropylene mesh with fibrin glue fixation. There were no statistically significant differences between the two groups with regard to intraoperative variables, early or late intraoperative complications, chronic pain or recurrence. Self-gripping mesh in transabdominal hernia repair was found to be a valid alternative to polypropylene mesh in terms of complications, recurrence and postoperative pain. The cost analysis and comparability of outcomes support the preferential use of self-gripping mesh. PMID:28352842
Choi, Kyung-Sik; Kim, Min-Su; Jang, Sung-Ho
2014-01-01
Recently, the increasing rates of facial nerve preservation after vestibular schwannoma (VS) surgery have been achieved. However, the management of a partially or completely damaged facial nerve remains an important issue. The authors report a patient who was had a good recovery after a facial nerve reconstruction using fibrin glue-coated collagen fleece for a totally transected facial nerve during VS surgery. And, we verifed the anatomical preservation and functional outcome of the facial nerve with postoperative diffusion tensor (DT) imaging facial nerve tractography, electroneurography (ENoG) and House-Brackmann (HB) grade. DT imaging tractography at the 3rd postoperative day revealed preservation of facial nerve. And facial nerve degeneration ratio was 94.1% at 7th postoperative day ENoG. At postoperative 3 months and 1 year follow-up examination with DT imaging facial nerve tractography and ENoG, good results for facial nerve function were observed. PMID:25024825
Zhou, Jinjun; Bhagat, Vrushali; Becker, Matthew L
2016-12-14
The adhesive nature of mussels arises from the catechol moiety in the 3,4-dihydroxyphenylalanine (DOPA) amino acid, one of the many proteins that contribute to the unique adhesion properties of mussels. Inspired by these properties, many biomimetic adhesives have been developed over the past few years in an attempt to replace adhesives such as fibrin, cyanoacrylate, and epoxy glues. In the present work, we synthesized ethanol soluble but water insoluble catechol functionalized poly(ester urea) random copolymers that help facilitate delivery and adhesion in wet environments. Poly(propylene glycol) units incorporated into the polymer backbone impart ethanol solubility to these polymers, making them clinically relevant. A catechol to cross-linker ratio of 10:1 with a curing time of 4 h exceeded the performance of commercial fibrin glue (4.8 ± 1.4 kPa) with adhesion strength of 10.6 ± 2.1 kPa. These adhesion strengths are significant with the consideration that the adhesion studies were performed under wet conditions.
Mechanical and chemical characteristics of an autologous glue.
De Somer, Filip; Delanghe, Joris; Somers, Pamela; Debrouwere, Maarten; Van Nooten, Guido
2008-09-15
The study evaluates the mechanical and chemical characteristics of autologous surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA). Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or 100 g/L) was used as a single protein set-up for testing tensile strength, elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/- 167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L. Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for BioGlue at maximum load. Autologous glues for vascular repair can be easily prepared out of the patient's plasma. The optimal characteristics, compared to BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue will exert less tensile strength than BioGlue but has a better compliance. In case where no plasma can obtained from the patient, mixing human albumin 200 g/L with GTA 75 g/L can be an alternative to BioGlue.
Xu, Wenjing; Zhao, Zhe; Zhao, Bin; Wang, Yu; Peng, Jiang; Zhang, Li; Chen, Jifeng; Lu, Shibi
2011-10-01
Bone marrow mesenchymal stem cells (BMSCs), as replacement cells of Schwann cells, can increase the effect of peripheral nerve repair. However, it has not yet reached any agreement to add the appropriate number of seeded cells in nerve scaffold. To investigate the effect of different number of BMSCs on the growth of rat dorsal root ganglia (DRG). Three 4-week-old Sprague Dawley (SD) rats (weighing 80-100 g) were selected to isolate BMSCs, which were cultured in vitro. Three 1- to 2-day-old SD rats (weighing 4-6 g) were selected to prepare DRG. BMSCs at passage 3 were used to prepare BMSCs-fibrin glue complex. According to different number of BMSCs at passage 3 in fibrin glue, experiment was divided into group A (1 x 10(3)), group B (1 x 10(4)), group C (1 x 10(5)), and group D (0, blank control), and BMSCs were co-cultured with rat DRG. The axon length of DRG, Schwann cell migration distance, and axon area index were quantitatively evaluated by morphology, neurofilament 200, and Schwann cells S-100 immunofluorescence staining after cultured for 48 hours. Some long cell processes formed in BMSCs at 48 hours; migration of Schwann cells and axons growth from the DRG were observed, growing in every direction. BMSCs in fibrin glue had the biological activity and could effect DRG growth. The axon length of DRG and Schwann cell migration distance in groups A, B, and C were significantly greater than those in group D (P < 0.05). The axon length of DRG and Schwann cell migration distance in group C were significantly less than those in group B (P < 0.05), but there was no significant difference between group A and group C, and between group A and group B (P > 0.05). The axon area index in groups A and B was significantly greater than that in group D (P < 0.05), but there was no significant difference between group C and group D (P > 0.05); there was no significant difference in groups A, B, and C (P > 0.05). In vitro study on DRG culture experiments is an ideal objective neural model of nerve regeneration. The effect of different number of BMSCs in fibrin glue on the growth of DRG has dose-effect relationship. It can provide a theoretical basis for the appropriate choice of the BMSCs number for tissue engineered nerve.
Sarin, Jussi; Hiltunen, Markus; Hupa, Leena; Pulkkinen, Jaakko; Vallittu, Pekka K
2016-09-28
Bioactive glass (BG)-containing fiber-reinforced composite implants, typically screw-retained, have started to be used clinically. In this study, we tested the mechanical strength of composites formed by a potential implant adhesive of n-butyl-2-cyanoacrylate glue and BG S53P4 particles. Water immersion for 3, 10 or 30 days had no adverse effect on the compression strength. When cyanoacrylate glue-BG-composites were subjected to simulated body fluid immersion, the average pH rose to 7.52 (SD 0.066) from the original value of 7.35 after 7 days, and this pH increment was smaller compared to BG particle-group or fibrin glue-BG-composite group. Based on these results n-butyl-2 cyanoacrylate glue, by potentially producing a strong adhesion, might be considered a possible alternative for fixation of BG S53P4 containing composite implants. However, the mechanical and solubility properties of the cyanoacrylate glue may not encourage the use of this tissue adhesive with BG particles.
A highly adhesive and naturally derived sealant.
Assmann, Alexander; Vegh, Andrea; Ghasemi-Rad, Mohammad; Bagherifard, Sara; Cheng, George; Sani, Ehsan Shirzaei; Ruiz-Esparza, Guillermo U; Noshadi, Iman; Lassaletta, Antonio D; Gangadharan, Sidhu; Tamayol, Ali; Khademhosseini, Ali; Annabi, Nasim
2017-09-01
Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.
What Is the Biological and Clinical Relevance of Fibrin?
Litvinov, Rustem I; Weisel, John W
2016-06-01
As our knowledge of the structure and functions of fibrinogen and fibrin has increased tremendously, several key findings have given some people a superficial impression that the biological and clinical significance of these clotting proteins may be less than earlier thought. Most strikingly, studies of fibrinogen knockout mice demonstrated that many of these mice survive to weaning and beyond, suggesting that fibrin(ogen) may not be entirely necessary. Humans with afibrinogenemia also survive. Furthermore, in recent years, the major emphasis in the treatment of arterial thrombosis has been on inhibition of platelets, rather than fibrin. In contrast to the initially apparent conclusions from these results, it has become increasingly clear that fibrin is essential for hemostasis; is a key factor in thrombosis; and plays an important biological role in infection, inflammation, immunology, and wound healing. In addition, fibrinogen replacement therapy has become a preferred, major treatment for severe bleeding in trauma and surgery. Finally, fibrin is a unique biomaterial and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier and/or a vector for targeted drug delivery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Autologous Fibrin Glue as an Encapsulating Scaffold for Delivery of Retinal Progenitor Cells
Ahmed, Tamer A. E.; Ringuette, Randy; Wallace, Valerie A.; Griffith, May
2015-01-01
The retina is a highly sophisticated piece of the neural machinery that begins the translation of incoming light signals into meaningful visual information. Several degenerative diseases of the retina are characterized by photoreceptor loss and eventually lead to irreversible blindness. Regenerative medicine, using tissue engineering-based constructs to deliver progenitor cells or photoreceptors along with supporting carrier matrix is a promising approach for restoration of structure and function. Fresh fibrin glue (FG) produced by the CryoSeal®FS system in combination with mouse retinal progenitor cells (RPCs) were evaluated in this study. In vitro expanded RPCs isolated from postnatal mouse retina were encapsulated into FG and cultured in the presence of the protease inhibitor, tranexamic acid. Encapsulation of RPCs into FG did not show adverse effects on cell proliferation or cell survival. RPCs exhibited fibroblast-like morphology concomitantly with attachment to the encapsulating FG surface. They expressed α7 and β3 integrin subunits that could mediate attachment to fibrin matrix via an RGD-independent mechanism. The three-dimensional environment and the attachment surface provided by FG was associated with a rapid down-regulation of the progenitor marker SOX2 and enhanced the expression of the differentiation markers cone-rod homeobox and recoverin. However, the in vitro culture conditions did not promote full differentiation into mature photoreceptors. Nevertheless, we have shown that autologous fibrin, when fabricated into a scaffold for RPCs for delivery to the retina, provides the cells with external cues that could potentially improve the differentiation events. Hence, transient encapsulation of RPCs into FG could be a valid and potential treatment strategy to promote retinal regeneration following degenerative diseases. However, further optimization is necessary to maximize the outcomes in terms of mature photoreceptors. PMID:25692127
Hart, Alexandra M; Duggal, Clarie; Pinell-White, Ximena; Losken, Albert
2017-04-01
Donor-site seroma is the most common complication following latissimus dorsi flap breast reconstruction. Various agents and techniques have attempted to minimize seroma formation. The purpose of this study was to compare the efficacy of different products and quilting sutures at seroma prevention. This is a single-center, double-blinded, randomized, controlled trial of a consecutive series of breast cancer patients (n = 96) undergoing latissimus dorsi flap reconstruction performed by a single surgeon. Patients were randomized to receive (1) fibrin glue (Tisseel) (n = 23), (2) triamcinolone acetonide (n = 26), or (3) normal saline (control) (n = 27) sprayed into the donor site. The fourth arm included donor-site quilting sutures (n = 20). Outcomes included seroma, drain output, and days to last drain removal. Drain removal was standardized at less than 30 cc/day. All groups were matched evenly without differences in risk, procedures, or complications. The overall seroma rate was 31.3 percent (n = 30). The quilting group had significantly less drainage for weeks 1 (p = 0.006) and 2 (p = 0.050) postoperatively. Quilting statistically reduced the incidence of seromas to 5.0 percent (n = 1; p = 0.038) compared with other groups (control, 34.5 percent; fibrin, 27.6 percent; and triamcinolone, 37.6 percent). Drains were removed 10 days earlier with quilting (control, 35.5 days; fibrin, 39.5 days; triamcinolone, 37.4 days; and quilting, 25.8 days; p = 0.001). The incidence of all other complications was similar between groups. The use of quilting donor sites significantly decreases the incidence of donor-site seromas and leads to earlier drain removal following latissimus dorsi flap reconstruction and maintains a low complication profile. Therapeutic, II.
Improved anti-tumor efficacy via combination of oxaliplatin and fibrin glue in colorectal cancer
Hu, Yuzhu; Yu, Ting; Liu, Xiaoxiao; He, Yihong; Deng, Lihong; Guo, Jiajuan; Hua, Yuanqi; Luo, Ting; Gao, Xiang
2018-01-01
Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8+ T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment. PMID:29416788
Fibrin glue for local haemostasis in haemophilia surgery.
Rodriguez-Merchan, E Carlos
2017-12-01
Local fibrin glue (FG) appears to be a useful local haemostatic agent for severe haemorrhage in people with haemophilia (PWH) undergoing surgical procedures. To evaluate the role of local FG in PWH. A review of the literature on the topic has been performed. Local FG is not always necessary to achieve haemostasis in all surgical procedures performed in PWH. However, it could be a good adjunct therapy, primarily when a surgical field will bleed more than expected (e.g. patients with inhibitors), and also for circumcisions, dental extractions, and surgical treatment of pseudotumours. Although correct surgical haemostasis can typically be achieved by the infusion of factor concentrate at the adequate dose, my recommendation for surgeons is always to have local FG by their side. Local FG appears to be an effective adjunctive therapy for cases in which bleeding is likely (e.g. patients with inhibitors), and for circumcisions, oral surgery, and treatment of pseudotumours. Through the use of local FG, the doses of factor concentrate necessary to prevent bleeding could be reduced, providing considerable cost savings.
Platelet rich fibrin: a new paradigm in periodontal regeneration.
Kumar, R Vinaya; Shubhashini, N
2013-09-01
Among the great challenges facing clinical research is the development of bioactive surgical additives regulating inflammation and increasing healing. Although the use of fibrin adhesives and platelet-rich plasma (PRP) is well documented, they have their own limitations. Hence, reconstructive dental surgeons are looking for an "edge" that jump starts the healing process to maximize predictability as well as the volume of regenerated bone. Overcoming the restrictions related to the reimplantation of blood-derived products, a new family of platelet concentrate, which is neither a fibrin glue nor a classical platelet concentrate, was developed in France. This second generation platelet concentrate called platelet-rich fibrin (PRF), has been widely used to accelerate soft and hard tissue healing. Its advantages over the better known PRP include ease of preparation/application, minimal expense, and lack of biochemical modification (no bovine thrombin or anticoagulant is required). This article serves as an introduction to the PRF "concept" and its potential clinical applications with emphasis on periodontal regeneration.
Carandina, S; Tabbara, M; Bossi, M; Valenti, A; Polliand, C; Genser, L; Barrat, Christophe
2016-02-01
Laparoscopic sleeve gastrectomy (LSG) is associated with serious complications, such as staple line (SL) leaks and bleeding. In order to prevent the occurrence of these complications, surgeons have advocated the need to strengthen the staple line. The aim of this randomized controlled study was to compare the efficacy of three different ways of strengthening of the SL in LSG in preventing surgical post-operative complications. Between April 2012 and December 2014, 600 patients (pts) scheduled for LSG were prospectively randomized into groups without SL reinforcement (group A) or with SL reinforcement including fibrin glue coverage (group B), or oversewn SL with imbricating absorbable (Monocryl™; group C) or barbed (V lock®) running suture (group D). Primary endpoints were post-operative leaks, bleeding, and stenosis, while secondary outcomes consisted of the time to perform the staple line reinforcement (SLR) and total operative time. Mean SLR operative time was lower for group B (3.4 ± 1.3 min) compared with that for groups C (26.8 ± 8.5 min) and D (21.1 ± 8.4 min) (p < 0.0001). Mean total operative time was 100.7 ± 16.4 min (group A), 104.4 ± 22.1 min (group B), 126.2 ± 18.9 min (group C), and 124.6 ± 22.8 (group D) (p < 0.0001). Post-operative leaks, bleeding, and stenosis were recorded in 14 pts (2.3 %), 5 pts (0.8 %), and 7 pts (1.1 %), respectively, without statistical difference between the groups. Our study suggests that SLR during LSG, with an imbricating or non-imbricating running suture or with fibrin glue, is an unrewarding surgical act with the sole effect of prolonging the operative time.
The properties of gelatin-poly (gamma-glutamic acid) hydrogels as biological glues.
Hsu, Shan-Hui; Lin, Chen-Huan
2007-01-01
The influence of the molecular weight and the type of gelatin (A or B), as well as the molecular weight of poly (gamma-glutamic acid) (gamma-PGA), on the properties of gelatin/gamma-PGA mixed bioadhesives were studied. The gelation of the system was enhanced by a crosslinker, 1-(3-dimethylaminopropyl)-3-(ethylcarbodiimide) hydrochloride (EDC). The gelation time of the bioadhesives was analyzed using rheological measurements. The results indicated that the type of gelatin was a critical factor in determining the gelation time of the biological glues. The mixed glues had greater bonding strength and smaller gelation times as the molecular weight of gamma-PGA or gelatin increased. The swelling ratio decreased and the denaturation temperature increased upon raising the EDC concentration, indicating a greater degree of crosslinking at higher EDC concentrations. The mixed glues crosslinked with various concentrations of EDC (1.7-2.5%) showed no cytotoxicity to fibroblasts. In addition, no significant inflammatory response was observed in the rat subcutaneous implantation. The bioadhesives based on gelatin/gamma-PGA remained at the site for 7 days while the fibrin glue had almost completely degraded. By choosing the appropriate gelatin type and higher molecular weight gamma-PGA in the mixtures, the gelatin/gamma-PGA biological glues could serve as soft tissue adhesives. Rheological characterization was essential in the evaluation of biological glues.
Lee, Hannah H.; Haleem, Amgad M.; Yao, Veronica; Li, Juan; Xiao, Xiao
2011-01-01
Fibrin glue (FG) is used in a variety of clinical applications and in the laboratory for localized and sustained release of factors potentially important for tissue engineering. However, the effect of different fibrinogen concentrations on FG scaffold delivery of bioactive adeno-associated viruses (AAVs) has not been established. This study was performed to test the hypothesis that FG concentration alters AAV release profiles, which affect AAV bioavailability. Gene transfer efficiency of AAV-GFP released from FG was measured using HEK-293 cells. Bioactivity of AAV transforming growth factor-beta1 (TGF-β1) released from FG was assessed using the mink lung cell assay, and by measuring induction of cartilage-specific gene expression in human mesenchymal stem cells (hMSCs). Nondiluted FG had longer clotting times, smaller pore sizes, thicker fibers, and slower dissolution rate, resulting in reduced release of AAV. AAV release and gene transfer efficiency was higher with 25% and 50% FG than with the 75% and 100% FG. AAV-TGF-β1 released from dilute-FG transduced hMSCs, resulting in higher concentrations of bioactive TGF-β1 and greater upregulation of cartilage-specific gene expression compared with hMSC from undiluted FG. This study, showing improved release, transduction efficiency, and chondrogenic effect on hMSC of bioactive AAV-TGF-β1 released from diluted FG, provides information important to optimization of this clinically available scaffold for therapeutic gene delivery, both in cartilage regeneration and for other tissue engineering applications. PMID:21449684
Bhandari, Vipul; Rao, Chandan Latha; Ganesh, Sri; Brar, Sheetal
2015-01-01
To evaluate the efficacy of conjunctival autograft after the pterygium excision with fibrin adhesive using conjunctiva over the pterygium. This prospective study included 25 eyes of 25 patients with a mean age of 40±10 years, who underwent the pterygium excision with conjunctival autograft derived from the body of the pterygium and attached using fibrin glue. The mean follow-up period was 6 months. On all postoperative visits, changes in uncorrected visual acuity, corrected distance visual acuity, astigmatism, complications, and the evidence of recurrence were recorded. At the end of mean follow-up, uncorrected visual acuity and corrected distance visual acuity improved by one or two lines in all eyes treated. Mean astigmatism reduced significantly from a preoperative value from 2.308D to 1.248D postoperatively (P<0.026). Minor postoperative complications such as congestion, chemosis, and subconjunctival hemorrhage were seen, which resolved with time. No major sight-threatening or graft-related complications were detected. There was no evidence of recurrence during a follow-up period of 6 months. Self-conjunctival autograft following the pterygium excision appears to be a feasible, safe, and effective alternative method for management of pterygium. It also preserves the superior conjunctiva for future surgeries. However, longer follow-up is required to study the long-term outcomes, especially the incidence of recurrence.
Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets.
Krishnan, Lissy K; Mohanty, Mira; Umashankar, P R; Lal, Arthur Vijayan
2004-11-01
Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing.
Surgical Reconstruction of Ocular Surface Tumors Using Fibrin Sealant Tissue Adhesive.
Queiroz de Paiva, Aline Roseane; Abreu de Azevedo Fraga, Larissa; Torres, Virgínia Laura Lucas
2016-10-01
To evaluate the surgical outcomes of ocular surface reconstruction in corneal-conjunctival tumors using fibrin tissue adhesive. A prospective noncomparative study was performed between May 2013 and February 2015. Patients were submitted to routine surgical procedure for corneal-conjunctival tumor excision followed by amniotic membrane graft transplantation using fibrin tissue adhesive (Evicel®, Omrix Biopharmaceuticals Ltd., Israel). Results were assessed on the 1st, 7th, 15th and 30th postoperative days to analyze subjective complaints, adhesiveness and positioning of the graft, potential complications and recurrences. Twenty-five eyes were analyzed (male, 14). The diagnosis after the treatment was categorized as squamous cell neoplasia, dysplasia, actinic keratosis, squamous papilloma and compound melanocytic nevus. Few significant symptoms were reported, such as mild hyperemia and ocular dyscomfort. One case developed a conjunctival granuloma which regressed after topical treatment. All grafts were successful with no displacements or retraction postoperatively. There was no clinical recurrence of the tumor in a mean time of follow-up of 11 months. Fibrin tissue adhesive is safe and effective in the surgery of ocular surface tumor. In this series, sutureless amniotic membrane transplantation using fibrin glue has the potential to shorten the surgical time, mitigate inflammation postoperatively and improve patient discomfort.
Arkudas, Andreas; Pryymachuk, Galyna; Hoereth, Tobias; Beier, Justus P; Polykandriotis, Elias; Bleiziffer, Oliver; Gulle, Heinz; Horch, Raymund E; Kneser, Ulrich
2012-07-01
In this study, different fibrin sealants with varying concentrations of the fibrin components were evaluated in terms of matrix degradation and vascularization in the arteriovenous loop (AVL) model of the rat. An AVL was placed in a Teflon isolation chamber filled with 500 μl fibrin gel. The matrix was composed of commercially available fibrin gels, namely Beriplast (Behring GmbH, Marburg, Germany) (group A), Evicel (Omrix Biopharmaceuticals S.A., Somerville, New Jersey, USA) (group B), Tisseel VH S/D (Baxter, Vienna, Austria) with a thrombin concentration of 4 IU/ml and a fibrinogen concentration of 80 mg/ml [Tisseel S F80 (Baxter), group C] and with an fibrinogen concentration of 20 mg/ml [Tisseel S F20 (Baxter), group D]. After 2 and 4 weeks, five constructs per group and time point were investigated using micro-computed tomography, and histological and morphometrical analysis techniques. The aprotinin, factor XIII and thrombin concentration did not affect the degree of clot degradation. An inverse relationship was found between fibrin matrix degradation and sprouting of blood vessels. By reducing the fibrinogen concentration in group D, a significantly decreased construct weight and an increased generation of vascularized connective tissue were detected. There was an inverse relationship between matrix degradation and vascularization detectable. Fibrinogen as the major matrix component showed a significant impact on the matrix properties. Alteration of fibrin gel properties might optimize formation of blood vessels.
Fabrication and physical and biological properties of fibrin gel derived from human plasma.
Zhao, Haiguang; Ma, Lie; Zhou, Jie; Mao, Zhengwei; Gao, Changyou; Shen, Jiacong
2008-03-01
The fast development of tissue engineering and regenerative medicine drives the old biomaterials, for example, fibrin glue, to find new applications in these areas. Aiming at developing a commercially available hydrogel for cell entrapment and delivery, in this study we optimized the fabrication and gelation conditions of fibrin gel. Fibrinogen was isolated from human plasma by a freeze-thaw circle. Gelation of the fibrinogen was accomplished by mixing with thrombin. Absorbance of the fibrinogen/thrombin mixture at 550 nm as a function of reaction time was monitored by UV-VIS spectroscopy. It was found that the clotting time is significantly influenced by the thrombin concentration and the temperature, while less influenced by the fibrinogen concentration. After freeze-drying, the fibrin gel was characterized by scanning electron microscopy (SEM), revealing fibrous microstructure. Thermal gravimetric analysis found that the degradation temperature of the crosslinked fibrin gel starts from 288 degrees C, which is about 30 degrees C higher than that of the fibrinogen. The hydrogel has an initial water-uptake ratio of approximately 50, decreased to 30-40 after incubation in water for 11 h depending on the thrombin concentration. The fibrin gels lost their weights in PBS very rapidly, while slowly in DMEM/fetal bovine serum and DMEM. In vitro cell culture found that human fibroblasts could normally proliferate in the fibrin gel with spreading morphology. In conclusion, the fibrin gel containing higher concentration of fibrinogen (20 mg ml(-1)) and thrombin (5 U ml(-1)) has suitable gelation time and handling properties, and thus is applicable as a delivery vehicle for cells such as fibroblasts.
Fabrication and physical and biological properties of fibrin gel derived from human plasma
NASA Astrophysics Data System (ADS)
Zhao, Haiguang; Ma, Lie; Zhou, Jie; Mao, Zhengwei; Gao, Changyou; Shen, Jiacong
2008-03-01
The fast development of tissue engineering and regenerative medicine drives the old biomaterials, for example, fibrin glue, to find new applications in these areas. Aiming at developing a commercially available hydrogel for cell entrapment and delivery, in this study we optimized the fabrication and gelation conditions of fibrin gel. Fibrinogen was isolated from human plasma by a freeze-thaw circle. Gelation of the fibrinogen was accomplished by mixing with thrombin. Absorbance of the fibrinogen/thrombin mixture at 550 nm as a function of reaction time was monitored by UV-VIS spectroscopy. It was found that the clotting time is significantly influenced by the thrombin concentration and the temperature, while less influenced by the fibrinogen concentration. After freeze-drying, the fibrin gel was characterized by scanning electron microscopy (SEM), revealing fibrous microstructure. Thermal gravimetric analysis found that the degradation temperature of the crosslinked fibrin gel starts from 288 °C, which is about 30 °C higher than that of the fibrinogen. The hydrogel has an initial water-uptake ratio of ~50, decreased to 30-40 after incubation in water for 11 h depending on the thrombin concentration. The fibrin gels lost their weights in PBS very rapidly, while slowly in DMEM/fetal bovine serum and DMEM. In vitro cell culture found that human fibroblasts could normally proliferate in the fibrin gel with spreading morphology. In conclusion, the fibrin gel containing higher concentration of fibrinogen (20 mg ml-1) and thrombin (5 U ml-1) has suitable gelation time and handling properties, and thus is applicable as a delivery vehicle for cells such as fibroblasts.
Effect of intracameral injection of fibrin tissue sealant on the rabbit anterior segment
Chew, Annabel C.Y.; Tan, Donald T.H.; Poh, Rebekah; HM, Htoon; Beuerman, Roger W.
2010-01-01
Purpose To investigate the effect of intracameral injection of fibrin tissue sealant on the anterior segment structures in a rabbit model. Methods One eye of 10 rabbits received an intracameral injection of fibrin tissue sealant with a thrombin concentration of 500 IU (TISSEEL), and the fellow eye received an intracameral injection of balanced salt solution as a control. The rabbits were followed up with serial slit-lamp examinations, photography, high resolution anterior segment optical coherence tomography scans with pachymetry measurement, and intraocular pressure (IOP) monitoring until complete dissolution of the fibrin sealant. Corneal endothelial cell viability was evaluated using live/dead cell assays. Apoptosis of the cornea and trabecular meshwork were evaluated using TUNEL assays. Ultra-structural examinations of the cornea and trabecular meshwork were performed using electron microscopy. Histology of the trabecular meshwork and iris were analyzed using light microscopy. Results The quantity of the intracameral fibrin sealant was shown to be significantly correlated with increased IOP and pachymetry post-operatively. Complete dissolution of the fibrin sealant occurred between 15 and 30 days. Live/dead cell assays showed no decrease in viability of the corneal endothelium, and TUNEL assays showed no increase in apoptosis of the corneal epithelium, stroma, endothelium, or trabecular meshwork in the eyes with the fibrin sealant. Light and electron microscopy of the anterior segment structures were unremarkable. Conclusion The intracameral use of fibrin glue was associated with a transient increase in IOP and pachymetry. However, there was no evidence of toxicity or structural damage to the corneal endothelium, trabecular meshwork, or iris. PMID:20596250
Synthetic vs natural scaffolds for human limbal stem cells
Tominac Trcin, Mirna; Dekaris, Iva; Mijović, Budimir; Bujić, Marina; Zdraveva, Emilija; Dolenec, Tamara; Pauk-Gulić, Maja; Primorac, Dragan; Crnjac, Josip; Špoljarić, Branimira; Mršić, Gordan; Kuna, Krunoslav; Špoljarić, Daniel; Popović, Maja
2015-01-01
Aim To investigate the impact of synthetic electrospun polyurethane (PU) and polycaprolactone (PCL) nanoscaffolds, before and after hydrolytic surface modification, on viability and differentiation of cultured human eye epithelial cells, in comparison with natural scaffolds: fibrin and human amniotic membrane. Methods Human placenta was taken at elective cesarean delivery. Fibrin scaffolds were prepared from commercial fibrin glue kits. Nanoscaffolds were fabricated by electrospinning. Limbal cells were isolated from surpluses of human cadaveric cornea and seeded on feeder 3T3 cells. The scaffolds used for viability testing and immunofluorescence analysis were amniotic membrane, fibrin, PU, and PCL nanoscaffolds, with or without prior NaOH treatment. Results Scanning electron microscope photographs of all tested scaffolds showed good colony spreading of seeded limbal cells. There was a significant difference in viability performance between cells with highest viability cultured on tissue culture plastic and cells cultured on all other scaffolds. On the other hand, electrospun PU, PCL, and electrospun PCL treated with NaOH had more than 80% of limbal cells positive for stem cell marker p63 compared to only 27%of p63 positive cells on fibrin. Conclusion Natural scaffolds, fibrin and amniotic membrane, showed better cell viability than electrospun scaffolds. On the contrary, high percentages of p63 positive cells obtained on these scaffolds still makes them good candidates for efficient delivery systems for therapeutic purposes. PMID:26088849
Kim, Yong Sang; Sung, Chang Hun; Chung, Sung Hoon; Kwak, Sang Joon; Koh, Yong Gon
2017-07-01
The mesenchymal stem cell (MSC)-based tissue engineering approach has been developed to improve the treatment of rotator cuff tears. Hypothesis/Purpose: The purpose was to determine the effect of an injection of adipose-derived MSCs loaded in fibrin glue during arthroscopic rotator cuff repair on clinical outcomes and to evaluate its effect on structural integrity using magnetic resonance imaging (MRI). The hypothesis was that the application of adipose-derived MSCs would improve outcomes after the surgical repair of a rotator cuff tear. Cohort study; Level of evidence, 3. Among 182 patients treated with arthroscopic surgery for a rotator cuff tear, 35 patients treated with arthroscopic rotator cuff repair alone (conventional group) were matched with 35 patients who underwent arthroscopic rotator cuff repair with an injection of adipose-derived MSCs loaded in fibrin glue (injection group) based on sex, age, and lesion size. Outcomes were assessed with respect to the visual analog scale (VAS) for pain, range of motion (ROM) (including forward flexion, external rotation at the side, and internal rotation at the back), and functional measures of the Constant score and University of California, Los Angeles (UCLA) shoulder rating scale. Repaired tendon structural integrity was assessed by using MRI at a minimum of 12 months after surgery, and the mean clinical follow-up was 28.8 ± 4.2 months in the conventional group and 28.3 ± 3.8 months in the injection group. The mean VAS score at rest and during motion improved significantly in both groups after surgery. However, there were no significant differences between the groups at the final follow-up ( P = .256 and .776, respectively). Compared with preoperative measurements, forward flexion and external rotation at the side significantly improved at the final follow-up in both groups (all P < .05). However, no significant improvements in internal rotation at the back were observed in either group ( P = .625 and .834 for the conventional and injection groups, respectively). There were also no significant differences between the groups at the final follow-up for any of the 3 ROM positions (all P > .05). The mean Constant score and UCLA score improved significantly in both groups after surgery, but there were no significant differences between the groups at the final follow-up ( P = .634 and .302, respectively). MRI indicated a retear rate of 28.5% in the conventional group and 14.3% in the injection group ( P < .001). This study revealed that an injection of adipose-derived MSCs loaded in fibrin glue during rotator cuff repair could significantly improve structural outcomes in terms of the retear rate. There were, however, no clinical differences in the 28-month period of follow-up. Although still in the early stages of application, MSC augmentation of surgical rotator cuff repair appears useful for providing an adequate biological environment around the repair site.
Lv, Jia; Xiu, Peng; Tan, Jie; Jia, Zhaojun; Cai, Hong; Liu, Zhongjun
2015-06-24
Electron beam melting (EBM)-fabricated porous titanium implants possessing low elastic moduli and tailored structures are promising biomaterials for orthopedic applications. However, the bio-inert nature of porous titanium makes reinforcement with growth factors (GFs) a promising method to enhance implant in vivo performance. Bone-morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) are key factors of angiogenesis and osteogenesis. Therefore, the present study is aimed at evaluating EBM-fabricated porous titanium implants incorporating GF-doped fibrin glue (FG) as composite scaffolds providing GFs for improvement of angiogenesis and osteogenesis in rabbit femoral condyle defects. BMP-2 and VEGF were added into the constituent compounds of FG, and then this GF-doped FG was subsequently injected into the porous scaffolds. In five groups of implants, angiogenesis and osteogenesis were evaluated at 4 weeks post-implantation using Microfil perfusion and histological analysis: eTi (empty scaffolds), cTi (containing undoped FG), BMP/cTi (containing 50 μg rhBMP-2), VEGF/cTi (containing 0.5 μg VEGF) and Dual/cTi (containing 50 μg rhBMP-2 and 0.5 μg VEGF). The results demonstrate that these composite implants are biocompatible and provide the desired gradual release of the bioactive growth factors. Incorporation of GF delivery, whether a single factor or dual factors, significantly enhanced both angiogenesis and osteogenesis inside the porous scaffolds. However, the synergistic effect of the dual factors combination was observable on angiogenesis but absent on osteogenesis. In conclusion, fibrin glue is a biocompatible material that could be employed as a delivery vehicle in EBM-fabricated porous titanium for controlled release of BMP-2 and VEGF. Application of this method for loading a porous titanium scaffold to incorporate growth factors is a convenient and promising strategy for improving osteogenesis of critical-sized bone defects.
Protective fibrin-sealed plication of the small bowel in recurrent laparotomy.
Holland-Cunz, S; Boelter, A V; Waag, K L
2003-09-01
Adhesions after recurrent abdominal operations remain extremely common and are sources of severe morbidity. Fibrin-glued plication of the small gut in a meander-like formation is supposed to guarantee a decreased risk of intestinal obstruction postoperatively. This retrospective study analyses the clinical outcome after recurrent laparotomy in children treated with bowel plication by fibrin sealant. The surgical technique of performing the fibrin-glued plication is rather simple and quick: after taking off all adhesions two to four loops of the small gut are positioned so that they lie side by side. Beginning proximal fibrin [Tissucol fibrin sealant (Baxter)] is applied between the loops; approximately 20-30 s are needed to keep the loops in position until the fibrin dries. This manoeuvre is continued until all of the small gut is fixed in one block. The gut is brought back into the abdominal cavity without loosening the loops. This fixed formation by sero-serosal adhesions or mesenterial plications is supposed to guarantee postoperative free passage. The charts of 60 children who had undergone a fibrin plication of the small bowel between 1991 and 1999 were evaluated. Additionally, questionnaires were sent to all patients, and they were invited for an examination. Sixty patients (38 boys and 22 girls) received a fibrin sealant plication because of recurrent laparotomies with heavily serosal defects or recurrent ileus because of adhesions. The youngest baby was 10 days. Since 23 patients were premature the oldest patient was 11 years old. There were no intraoperative complications attributed to the method. In the postoperative period 7/60 (12%) patients had a recurrent ileus or subileus, leading in three (5%) patients to an early relaparotomy. The fibrin-glued plication of the small bowel decreases the risk of recurrent ileus or subileus considering the high figures in the literature concerning this issue. The time-saving method is very simple and easily feasible. No side effects after the treatment with fibrin glue were observed.
The Use of Stitching and Bioabsorbable Mesh and Glue to Combat Prolonged Air Leaks.
Tanaka, Toshiki; Ueda, Kazuhiro; Murakami, Junichi; Hamano, Kimikazu
2018-05-15
Prolonged postoperative air leaks are associated with extended periods of postoperative hospitalization, increased hospital costs, and an increased incidence of major cardiopulmonary complications. To prevent prolonged air leaks, we used small pieces of polyglycolic acid mesh as a pledget during the stitching of air leak sites. The stitched sites were then covered with mesh and fibrin glue. This novel technique showed the highest airway pressure tolerance in an ex vivo experimental study. There were no incidents of prolonged air leak among the five clinical cases in which this technique was initially applied. A large-scale study of patients with a high risk of prolonged air leak is warranted. Copyright © 2018. Published by Elsevier Inc.
Han, Hyun Ho; Jun, Daiwon; Moon, Suk-Ho; Kang, In Sook; Kim, Min Cheol
2016-01-01
For skin defects caused by full-thickness burns, trauma, or tumor tissue excision, skin grafting is one of the most convenient and useful treatment methods. In this situation, graft fixation is important in skin grafting. This study was performed to compare the effectiveness of skin graft fixation between high-concentration fibrin sealant and sutures. There have been numerous studies using fibrin sealant for graft fixation, but they utilized slow-clotting fibrin sealant containing less than 10 IU/mL thrombin. Twenty-five patients underwent split-thickness skin grafting using fast-clotting fibrin sealant containing 400 IU/mL thrombin, while 30 patients underwent grafting using sutures. Rates of hematoma/seroma formation, graft dislocation, graft necrosis, and graft take were investigated postoperatively. The graft surface area was calculated using Image J software (National Institutes of Health, Bethesda, MD, USA). After 5 days, rates of hematoma/seroma formation and graft dislocation were 7.84 and 1.29% in group I, and 9.55 and 1.45% in group II, respectively. After 30 days, rates of graft necrosis and graft take were 1.86 and 98.14% in group I, and 4.65 and 95.35% in group II. Undiluted fibrin sealant showed significantly superior results for all rates ( p < 0.05) except graft dislocation. When high-concentration fast-clotting fibrin sealant was applied to skin grafts without dilution, no difficulty was experienced during surgery. Sealant showed superior results compared with sutures and had an excellent graft take rate. II.
Mehdizadeh, M. Reza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian
2012-01-01
The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:22902057
Enterocutaneous fistula: a review of 82 cases.
Njeze, G E; Achebe, U J
2013-01-01
Enterocutaneous fistula is an unpleasant and troublesome complication of abdominal operations. The objective was to review the outcome of treatment of patients treated for enterocutaneous fistula. This is a retrospective study of 82 teenage and adult patients, who suffered from enterocutaneous fistula, seen over an 11 year period, in the University of Nigeria Teaching Hospital, Enugu. Patients' charts were reviewed for biodata, etiology of the fistula, volume of the fistula output, and result of treatment. Majority of the fistulas occurred after abdominal operations; many by general practitioners. After treatment for correction of fluid and electrolyte deficits, they were all tried on conservative therapy with enteral nutritional support as the main stay of management. Those, whose fistulas did not close, underwent surgical treatment. Total parenteral nutrition, octreotide, fibrin glue, and wound vacuum assisted closure (VAC) were not used for treating these patients. Spontaneous healing of fistulas occurred in 26 patients (31.7%), whereas 42 patients out of 50 (84%) healed after definitive operation. Fourteen patients (17%) in this study, died. Proper management of fluid and electrolyte imbalances, enteral nutritional support, control of sepsis and correctly timed surgical therapy, resulted in this good healing rate and acceptable mortality, without the use of parenteral nutrition, biologic fibrin glue injection or VAC. Suggestions are offered about steps that may help in eradicating some of these enterocutaneous fistulas.
Safety and efficacy of fibrin glue versus infinity suture in SICS with extended scleral flap
Ambastha, Anita; Kusumesh, Rakhi; Bhasker, Gyan; Sinha, Bibhuti Prassan
2018-01-01
Purpose: To study the safety and efficacy of biologic fibrin glue (FG) in comparison with infinity suture in SICS with compromised scleral flap. Methods: A retrospective comparative study of patients who were treated with FG (Group A) with 10–0 nylon (Group B) as sealing agent for intraoperative compromised tunnels in SICS. Parameters noted were postoperative inflammation, wound integrity, anterior chamber (AC) depth, intraocular pressure (IOP), and surgically induced astigmatism (SIA) at postoperative day 1, 4 weeks, 6 weeks, and 6 months, respectively. Epi Info 7 software and SIA calculator, Version 2.1 were used to analyze the result. Results: We reviewed the two groups of 18 patients each and noted that there was no statistically significant difference in postoperative inflammation (P > 0.05), AC depth (P > 0.05), and IOP (P > 0.05) between both groups at each postoperative visit. One patient in Group A showed postoperative shallow AC and subconjunctival bleb. Exposed sutures causing foreign body sensation had to be removed in five patients in Group B. At the end of 6-month postoperative period, no statistically significant difference was found in SIA (P = 0.92) between the two groups. Conclusion: Biologic FG can be safely used in securing the compromised scleral incisions in SICS. It also avoids suture-related complications. PMID:29676309
Nakamura, Hiroshi; Matsuyama, Yukihiro; Yoshihara, Hisatake; Sakai, Yoshihito; Katayama, Yoshito; Nakashima, Shojiro; Takamatsu, Jyunki; Ishiguro, Naoki
2005-07-01
A prospective randomized study evaluating the efficacy of autologous fibrin tissue adhesive for decreasing postoperative cerebrospinal fluid (CSF) leak in spinal cord surgery. To compare postoperative CSF leak in 3 groups (i.e., autologous fibrin tissue adhesive used, commercial fibrin glue used, and no fibrin tissue adhesive used) of patients undergoing spinal surgery who needed dural incision. Spinal cord operations, particularly when dural incision is inevitable, sometimes involve postoperative CSF leak. Because CSF leak is a serious complication, countermeasure is necessary to prevent it after dural suture. Commercial fibrin tissue adhesive was formerly used. Because the possibility of prion infection was widely noticed, commercial fibrin tissue adhesive containing animal components has been used less often. In 13 of 39 cases in which dural incision would be made, 400 mL whole blood was drawn, and autologous fibrin tissue adhesive was made of plasma. Cases were divided into 3 groups: (1) dural closure alone, (2) use of autologous fibrin tissue adhesive after dural closure, and (3) use of commercial fibrin tissue adhesive after dural closure. The primary outcome measure was determined as postoperative (3 days) volume of drainage fluid, and results were analyzed using the analysis of variance. The secondary outcome measure was general blood test, coagulation assay, and plasma fibrinogen, and these were analyzed also using the analysis of variance. There was a significant difference in the primary outcome between the autologous and control groups. No complications such as infection or continuous CSF leak were observed in any case. The mean volume of drainage fluid was 586.2 mL in the group with autologous fibrin tissue adhesive and 1026.1 mL in the group without fibrin tissue adhesive. The volume of drainage fluid was significantly lower in the former group than that in the latter group. There was no statistical difference between the volumes of the group with autologous adhesive and with commercial adhesive (639.2 mL). We used autologous fibrin tissue adhesive as a new sealant after dural closure instead of commercial fibrin tissue adhesive. No definitive CSF leak was observed, and the volume of drainage fluid was significantly lower in the group with autologous fibrin tissue adhesive than that in the group without fibrin tissue adhesive. The use of autologous fibrin tissue adhesive was superior to that of commercial fibrin tissue adhesive in cost.
Chen, Chia-Chun; Liao, Cheng-Hao; Wang, Yao-Horng; Hsu, Yuan-Ming; Huang, Shih-Horng; Chang, Chih-Hung; Fang, Hsu-Wei
2012-03-01
Extracellular matrix (ECM) is thought to participate significantly in guiding the differentiation process of mesenchymal stem cells (MSCs). In this study, we hypothesized that cartilage fragments from osteoarthritic knee could promote chondrogenesis of MSCs. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery. Cartilage fragments and MSCs were wrapped into fibrin glue; and the constructs were implanted subcutaneously into nude mice. Histological analysis showed neocartilage-like structure with positive Alcian blue staining in the cartilage fragment-fibrin-MSC constructs. However, constructs with only MSCs in fibrin showed condensed appearance like MSCs in the pellet culture. Gene expression of type II collagen in the constructs with 60 mg cartilage fragments were significantly elevated after 4 weeks of implantation. Conversely, the constructs without cartilage fragments failed to express type II collagen, which indicated MSCs did not differentiate into a chondrogenic lineage. In conclusion, we demonstrated the effect of cartilage fragments from osteoarthritic knee in promoting chondrogenic differentiation of MSCs. This may be a favorable strategy for MSC chondrogenesis without exogenous growth factor induction. Copyright © 2011 Orthopaedic Research Society.
NASA Astrophysics Data System (ADS)
Mehdikhani, Mehdi; Ghaziof, Sharareh
2018-01-01
In this research, poly-ɛ-caprolactone (PCL), polyethylene glycol (PEG), multi-wall carbon nanotubes (MWCNTs), and nanocomposite scaffolds containing 0.5 and 1% (w/w) MWCNTs coated with fibrin glue (FG) were prepared via solvent casting and freeze-drying technique for cardiac tissue engineering. Scanning electron microscopy, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray diffraction were used to characterize the samples. Furthermore, mechanical properties, electrical conductivity, degradation, contact angle, and cytotoxicity of the samples were evaluated. Results showed the uniform distribution of the MWCNTs with some aggregates in the prepared nanocomposite scaffolds. The scaffolds containing 1% (w/w) MWCNTs with and without FG coating illustrated optimum modulus of elasticity, high electrical conductivity, and wettability compared with PCL/PEG and PCL/PEG/0.5%(w/w) MWCNTs' scaffolds. FG coating enhanced electrical conductivity and cell response, and increased wettability of the constructs. The prepared scaffolds were degraded significantly after 60 days of immersion in PBS. Meanwhile, the nanocomposite containing 1% (w/w) MWCNTs with FG coating (S3) showed proper spreading and viability of the myoblasts seeded on it after 1, 4, and 7 days of culture. The scaffold containing 1% (w/w) MWCNTs with FG coating demonstrated optimal properties including acceptable mechanical properties, proper wettability, high electrical conductivity, satisfactory degradation, and excellent myoblasts response to it.
Antitumor effect of fibrin glue containing temozolomide against malignant glioma
Anai, Shigeo; Hide, Takuichiro; Takezaki, Tatsuya; Kuroda, Jun-ichiro; Shinojima, Naoki; Makino, Keishi; Nakamura, Hideo; Yano, Shigetoshi; Kuratsu, Jun-ichi
2014-01-01
Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma. PMID:24673719
Matsuzuka, Takashi; Suzuki, Masahiro; Ikeda, Masakazu; Sato, Kaoru; Fujimoto, Junko; Hosaka, Rumi; Tanji, Yuko; Soeda, Shu; Murono, Shigeyuki
2018-04-01
The aim of this case report was to evaluate the usefulness of a grafting with polyglycolic acid sheet and a fibrin glue spray (PGA sheet grafting) after resection of a cervical skin tumor. A 61-year-old woman presented with left cervical skin tumor resistance to chemo-radiotherapy. She had been undergoing multimodal therapy for ovarian serous papillary adenocarcinoma for the previous six years. Although she had a poor general condition and a cervical skin tumor of 9cm in diameter, which was painful and easy bleeding, had offensive smell, she hoped to return to her job. Under local anesthesia, resection was performed, and PGA sheet grafting were used to shield the skin defect. After resection, she was relieved from pain, and could stay home without daily wound treatment. One and half months after resection, the wound was almost epithelialized. The PGA sheets consist of soft, elastic, nonwoven fabric made of PGA. In recent years, PGA sheet grafting has been widely used in the reconstruction and was chosen to shield the skin defect for this case. PGA sheet grafting after resection of cervical skin tumor can be an acceptable method for palliative care to relieve pain, bleeding, offensive smell, and ugly appearance. Copyright © 2017 Elsevier B.V. All rights reserved.
Shintani, Yasushi; Inoue, Masayoshi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Okumura, Meinoshin
2015-10-01
Intraoperative alveolar air leaks remain a significant problem in thoracoscopic surgery (TS) cases. We examined the usefulness of covering damaged lung tissue with a subcutaneous fat pad for preventing postoperative air leakage in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC underwent a thoracoscopic lobectomy or segmentectomy. When alveolar air leakage from the superficial pulmonary parenchyma was found, fibrin glue in combination with an absorbable mesh sheet was applied (S group; n = 100). When leakage originated from deep within the pulmonary parenchyma, a subcutaneous fat pad about 2 × 2 cm in size was harvested from the utility incision and placed on the damaged lung tissue with fibrin glue and sutures (F group; n = 66). Patient characteristics, air leak duration, and chest-tube removal time were analyzed. The homogeneity of each group was consistent, with no statistical differences for age, respiratory function, surgical procedures, pathologic stage, and histological type. The air leak duration was significantly shorter (p = 0.015), and the chest tube was removed significantly earlier (p = 0.002) in patients in the F group. Use of a free subcutaneous fat pad during pulmonary resection for TS patients with NSCLC reduced the duration of air leakage and chest tube drainage. The present method is easy, safe, and effective for repairing an air leak from remaining lung tissues in such cases.
Mochizuki, Yumi; Tomioka, Hirofumi; Tushima, Fumihiko; Shimamoto, Hiroaki; Hirai, Hideaki; Oikawa, Yuu; Harada, Hiroyuki
2016-01-01
Purpose: This study aimed to evaluate the coverage of oral wounds using either a polyglycolic acid (PGA) sheet or split-thickness skin grafting (STSG). Materials and Methods: A total of 119 cases of wound coverage using a PGA sheet and fibrin glue spray as well as 132 cases of wound coverage cases using STSG were reviewed retrospectively. The site of the excision area, perioperative conditions, and postoperative functional problems were evaluated. Results: The PGA group had significantly shorter operation time, earlier start of oral intake, and shorter hospitalization than the STSG group. If the PGA sheet over the wound with exposed bone could be protected by a surgical sprint, oral food intake could be started on the day after surgery at the earliest. When the size of the wound in the buccal excisional area was classified into two groups (<6 or ≥6 cm2), mouth opening in the STSG group was significantly larger at 3 months postoperatively. When the size of the wound in the tongue and floor of mouth was classified into two groups (<12 or ≥12 cm2), the STSG group had a significantly higher score in postoperative speech intelligibility. Conclusion: Selection of a PGA sheet or STSG based on the consideration of defect size, tumor location, patients’ local and general condition and tolerance for surgery could reduce the patients’ postsurgical dysfunctional problems. PMID:28299263
NASA Astrophysics Data System (ADS)
Hopf, Barbara; Koch, Alexander W.; Roths, Johannes
2016-05-01
Glue-induced stresses decrease the accuracy of surface-mounted fiber Bragg gratings (FBG). Significant temperature dependent glue-induced birefringence was verified when a thermally cured epoxy-based bonding technique had been used. Determining the peak separation of two azimuthally aligned FBGs in PM fibers combined with a polarization resolved measurement set-up in a temperature range between -30°C and 150°C revealed high glue-induced stresses at low temperatures. Peak separations of about 60 pm and a nonlinear temperature dependence of the glue-induced birefringence due to stress relaxation processes and a visco-elastic behavior of the used adhesive have been shown.
[Pterygium surgery and fibrin glue: avoiding dehiscence].
Pérez-Silguero, D; Díaz-Ginory, A; Santana-Rodríguez, C; Pérez-Silguero, M A
2014-01-01
The purpose of the study is to evaluate those cases of pterygium surgery with fibrin sealant that produced dehiscence of the graft, and then apply and evaluate the efficacy of a different surgical technique in an attempt eliminate this complication in previously identified cases of high risk. The first phase is a retrospective study of 42 cases of pterygium surgery. In the second phase, the variation in the surgical technique was prospectively used in 14 cases of pterygium surgery. Cases of recurrent pterygium, broad pterygium, and complicated surgery were identified as the groups with a risk of suffering dehiscence of the graft. With the variant applied surgery no dehiscence occurred when using the variation in surgical technique, with no added complications. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.
Olmi, Stefano; Scaini, Alberto; Erba, Luigi; Bertolini, Aimone; Croce, Enrico
2007-11-01
Laparoscopic repair of inguinal hernias is usually achieved by totally extraperitoneal (TEP) or transabdominal preperitoneal (TAPP) techniques. The intraperitoneal onlay mesh (IPOM) could be an interesting alternative as it is much easier to perform and faster to execute. This technique is subject to correct selection of indications and to demonstration of its safety. From January 2003 to January 2006 we performed 61 laparoscopic hernia procedures on 60 selected patients (60 males with a mean age of 60 and mean weight of 76 kg) with an IPOM technique combining the Parietex composite mesh (12 cm circular model) and a fibrin glue (Tissucol) for its fixation. The glue was diluted to increase fixation time and applied to the mesh prior to positioning on the hernia defect. Mean operative time was 10 minutes. Mean hernia diameter was 2.5 cm (+/- 0.8 cm). 10 hernias were direct, 51 were indirect and 10 out of 61 were recurrent. We did not convert any of the laparoscopic procedures. Mean hospital stay was one day; mean recovery time for working and general physical activities was five days. Patients were checked after one week, 1-3-6 months and 1-2 years. Average follow up time was 23.7 months. 1.6 % of patients showed short-term complications: one trocar site haematoma. No additional complications were reported; particularly, we had no recurrence, no seroma, no mesh migration, and no bowel obstruction or fistula. Results of this study show intraperitoneal (IP) tolerance to this kind of mesh and the safety of its fixation with Tissucol. The absence of recurrence and complications could be a good reason to extend the indication of IPOM hernia repair. However, these preliminary results should be confirmed by longer follow-up.
Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen.
Hsieh, Jessica Y; Smith, Tim D; Meli, Vijaykumar S; Tran, Thi N; Botvinick, Elliot L; Liu, Wendy F
2017-01-01
Fibrin is a major component of the provisional extracellular matrix formed during tissue repair following injury, and enables cell infiltration and anchoring at the wound site. Macrophages are dynamic regulators of this process, advancing and resolving inflammation in response to cues in their microenvironment. Although much is known about how soluble factors such as cytokines and chemokines regulate macrophage polarization, less is understood about how insoluble and adhesive cues, specifically the blood coagulation matrix fibrin, influence macrophage behavior. In this study, we observed that fibrin and its precursor fibrinogen elicit distinct macrophage functions. Culturing macrophages on fibrin gels fabricated by combining fibrinogen with thrombin stimulated secretion of the anti-inflammatory cytokine, interleukin-10 (IL-10). In contrast, exposure of macrophages to soluble fibrinogen stimulated high levels of inflammatory cytokine tumor necrosis factor alpha (TNF-α). Macrophages maintained their anti-inflammatory behavior when cultured on fibrin gels in the presence of soluble fibrinogen. In addition, adhesion to fibrin matrices inhibited TNF-α production in response to stimulation with LPS and IFN-γ, cytokines known to promote inflammatory macrophage polarization. Our data demonstrate that fibrin exerts a protective effect on macrophages, preventing inflammatory activation by stimuli including fibrinogen, LPS, and IFN-γ. Together, our study suggests that the presentation of fibrin(ogen) may be a key switch in regulating macrophage phenotype behavior, and this feature may provide a valuable immunomodulatory strategy for tissue healing and regeneration. Fibrin is a fibrous protein resulting from blood clotting and provides a provisional matrix into which cells migrate and to which they adhere during wound healing. Macrophages play an important role in this process, and are needed for both advancing and resolving inflammation. We demonstrate that culture of macrophages on fibrin matrices exerts an anti-inflammatory effect, whereas the soluble precursor fibrinogen stimulates inflammatory activation. Moreover, culture on fibrin completely abrogates inflammatory signaling caused by fibrinogen or known inflammatory stimuli including LPS and IFN-γ. Together, these studies show that the presentation of fibrin(ogen) is important for regulating a switch between macrophage pro- and anti-inflammatory behavior. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Comparison of synthetic glues and 10-0 nylon in rabbit lamellar keratoplasty.
Cho, Soon Young; Kim, Man Soo; Oh, Su Ja; Chung, Sung Kun
2013-09-01
To evaluate changes in mean keratometry and to compare wound repair with corneal lamellar grafts in rabbit eyes using human synthetic tissue adhesives and 10-0 nylon. Corneal grafts were made using a 6.0-mm-diameter trephine and blades in the eyes of 15 New Zealand white rabbits. Human fibrin tissue adhesive (Tisseel) was used in group 1, human fibrin tissue adhesive (Beriplast P) was used in group 2, polyethylene glycol adhesive (Coseal) was used in group 3, and 8 bite sutures with 10-0 nylon were used in group 4 (control) for lamellar keratoplasty. Four bite sutures were made with 10-0 nylon in groups 1, 2, and 3. Slit-lamp microscopy and keratometry were performed at 3 days and 1, 2, and 4 weeks after the surgery. Histopathologic and electromicroscopic examinations were performed 4 weeks after the surgery. No inflammation or corneal toxicity was seen in groups 1 and 2. Histologically, a few inflammatory cells were seen in groups 3 and 4. Groups 1, 2, and 3 showed no statistically significant changes in mean keratometry at 4 weeks postoperatively compared with preoperative mean keratometry (Wilcoxon signed-rank test, P = 0.178, 0.208, and 0.889, respectively). The control group showed significant changes in mean keratometry at 4 weeks postoperatively (Wilcoxon signed-rank test, P = 0.018). Human fibrin tissue adhesives were well tolerated in rabbit eyes, with no apparent corneal toxicity. Polyethylene glycol adhesive showed more inflammation and insufficient wound repair compared with human fibrin tissue adhesives. Therefore, human fibrin tissue adhesives can be used as an alternative to sutures in lamellar keratoplasty.
Ryttlefors, Mats; Latini, Francesco; Basma, Jaafar; Krisht, Ali F
2016-07-01
Objective Recurrent brain tumors represent a challenge for neurosurgeons because of the extensive blood loss and the time needed for surgical resection. Only a few hemostatic agents are useful to prevent the bleeding and thus facilitate the surgical resection. Fibrin sealant can be used to achieve sealing, tissue adherence, or hemostasis when other means of hemostasis are inadequate or inappropriate. We report the feasibility and positive effects of direct intratumoral injection of fibrin sealant during resection of a recurrent hemangiopericytoma. Material and Methods The intraoperative intratumoral injection of fibrin sealant changed the tumor properties of a recurrent hemangiopericytoma of the tentorium with infra- and supratentorial extension. From a loose friable briskly bleeding tumor, this complex lesion became a nonbleeding well-demarcated soft-firm tumor that could easily be dissected off the pial surface and totally resected without extensive bleeding. Results There are several benefits of intratumoral injection of fibrin sealant in hemangiopericytomas: (1) the extensive bleeding is diminished and blood loss minimized; (2) the restriction of the surgical view by the venous oozing is diminished, making the microsurgical dissection of the tumor capsule off the pial surface easier and safer; (3) the loose consistency of the tumor becomes firmer and facilitates the manipulation of the tumor and leads to a safer resection; and (4) a shorter operating time is needed. Conclusion The use of intratumoral fibrin glue injection is a safe and useful technique that could be used for hemostasis of highly vascularized tumors to facilitate a safer resection and to reduce blood loss. Georg Thieme Verlag KG Stuttgart · New York.
Antibacterial effects of fibrin glue-antibiotic mixtures.
Kram, H B; Bansal, M; Timberlake, O; Shoemaker, W C
1991-02-01
In the present in vitro study, we investigated the duration of action and antibacterial effects of nonautologous fibrin glue (FG) combined with antibiotics (Abs) including Ciprofloxacin, Teicoplanin, Cefoxitin, and Gentamicin; the effect of FG alone on bacterial growth was also evaluated. The rate of Ab diffusion from combined FG-Ab clots was evaluated by separate elution with pooled human serum (HS) and normal saline (NS); supernatants were removed daily and assayed for active concentrations of each Ab. The effects of FG and combined FG-Ab clots on bacterial growth were evaluated by inoculating brain-heart infusion (BHI) with Staphylococcus aureus, followed by the addition of FG or FG-Ab clots; a separate set of studies was also performed with the addition of mouse lung homogenate (MLH) as well. The addition of Ab to FG clots resulted in continuous diffusion of the Ab into the surrounding HS or NS for up to 5 to 7 days; however, more than two-thirds of the Ab diffused out within 2 to 3 days regardless of the Ab used. The antibacterial effects of FG-Ciprofloxacin and FG-Teicoplanin clots were significant compared to those of FG clots not containing Ab. In addition, the presence of FG clots (in BHI) resulted in a reduction in bacterial growth compared to that of BHI alone. The addition of MLH to BHI resulted in increased bacterial growth, but this effect was inhibited by the presence of combined FG-Ab clots.(ABSTRACT TRUNCATED AT 250 WORDS)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aoyagi, Yasuyuki; Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba; Kuroda, Masayuki, E-mail: kurodam@faculty.chiba-u.jp
Adipose tissue is expected to provide a source of cells for protein replacement therapies via auto-transplantation. However, the conditioning of the environment surrounding the transplanted adipocytes for their long-term survival and protein secretion properties has not been established. We have recently developed a preparation procedure for preadipocytes, ceiling culture-derived proliferative adipocytes (ccdPAs), as a therapeutic gene vehicle suitable for stable gene product secretion. We herein report the results of our evaluation of using fibrin glue as a scaffold for the transplanted ccdPAs for the expression of a transduced gene in a three-dimensional culture system. The ccdPAs secreted the functional proteinmore » translated from an exogenously transduced gene, as well as physiological adipocyte proteins, and the long viability of ccdPAs (up to 84 days) was dependent on the fibrinogen concentrations. The ccdPAs spontaneously accumulated lipid droplets, and their expression levels of the transduced exogenous gene with its product were maintained for at least 56 days. The fibrinogen concentration modified the adipogenic differentiation of ccdPAs and their exogenous gene expression levels, and the levels of exogenously transduced gene expression at the different fibrinogen concentrations were dependent on the extent of adipogenic differentiation in the gel. These results indicate that fibrin glue helps to maintain the high adipogenic potential of cultured adipocytes after passaging in a 3D culture system, and suggests that once they are successfully implanted at the transplantation site, the cells exhibit increased expression of the transduced gene with adipogenic differentiation.« less
Lan, Aihua; Xiao, Feifan; Wang, Yun; Luo, Zhen; Cao, Qixin
2017-06-20
Previous meta-analyses have been conducted to compare the efficacy of fibrin glue (FG) versus sutures in pterygium surgery; however, additional clinical trials have since been published. Therefore, we conducted an updated meta-analysis to further explore the association between FG application in pterygium surgery, and the recurrence rate, complication rate, and surgical duration. An electronic literature search for eligible studies published before July 29, 2016 was conducted across multiple databases. Odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CI) were calculated. Publication bias of the included articles was evaluated by funnel plots. Differences in recurrence rate and complication rate between the FG and suture groups were evaluated in terms of OR with 95% CI, and SMD with 95% CI were used to estimate the difference in surgical duration. Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Twenty-four studies were included in this study. The pooled ORs for recurrence rate and complication rate were 0.35 and 1.121, respectively. The pooled SMD for surgical duration was -4.142. The TSA results indicated that evidence of the effect was sufficient in the recurrence group and surgical duration group. Although there was no difference in complication rate between FG and sutures, the apparent advantages of FG over sutures are shorter surgical duration and greater reduction in the recurrence rate of pterygium.
Experimental Study on the Viscosity and Adhesive Performance of Exogenous Liquid Fibrin Glue
HAYASHI, Takuro; HASEGAWA, Mitsuhiro; INAMASU, Joji; ADACHI, Kazuhide; NAGAHISA, Shinya; HIROSE, Yuichi
2014-01-01
Exogenous fibrin glue (FG) is highly suitable for neurosurgical procedures, because of its viscosity and adhesive properties. Several FGs are commercially available, but only few reports detail their differences. In the present study, we investigated the viscosity and adhesive performance of two types of FG: one is derived from blood donated in Europe and the United States (CSL Behring's Beriplast®, BP) and the other is derived from blood donated in Japan (the Chemo-Sero-Therapeutic Research Institute's Bolheal®, BH). The viscosity test that measured fibrinogen viscosity revealed that BP had significantly higher viscosity than BH. Similarly, the dripping test showed that BP traveled a significantly shorter drip distance in the vertical direction than BH, although the transverse diameter of the coagulated FG did not differ statistically significantly. In the tensile strength test, BP showed superior adhesion performance over BH. The histological study of the hematoxylin-eosin-stained specimens in both groups showed favorable adhesion. Although further studies are required on its manufacturing and usage methods, FG shows differences in viscosity and adhesive performance according to the blood from which it is derived. We conclude that it is desirable to select the type and usage method of FG according to the characteristics of the surgical operation in question. Our findings suggest that FG produced from the blood donated in Europe and the United States might be more suitable for use in surgical procedures that demand an especially high degree of viscosity and rapid adhesive performance. PMID:25367586
Experimental study on the viscosity and adhesive performance of exogenous liquid fibrin glue.
Hayashi, Takuro; Hasegawa, Mitsuhiro; Inamasu, Joji; Adachi, Kazuhide; Nagahisa, Shinya; Hirose, Yuichi
2014-01-01
Exogenous fibrin glue (FG) is highly suitable for neurosurgical procedures, because of its viscosity and adhesive properties. Several FGs are commercially available, but only few reports detail their differences. In the present study, we investigated the viscosity and adhesive performance of two types of FG: one is derived from blood donated in Europe and the United States (CSL Behring's Beriplast(®), BP) and the other is derived from blood donated in Japan (the Chemo-Sero-Therapeutic Research Institute's Bolheal(®), BH). The viscosity test that measured fibrinogen viscosity revealed that BP had significantly higher viscosity than BH. Similarly, the dripping test showed that BP traveled a significantly shorter drip distance in the vertical direction than BH, although the transverse diameter of the coagulated FG did not differ statistically significantly. In the tensile strength test, BP showed superior adhesion performance over BH. The histological study of the hematoxylin-eosin-stained specimens in both groups showed favorable adhesion. Although further studies are required on its manufacturing and usage methods, FG shows differences in viscosity and adhesive performance according to the blood from which it is derived. We conclude that it is desirable to select the type and usage method of FG according to the characteristics of the surgical operation in question. Our findings suggest that FG produced from the blood donated in Europe and the United States might be more suitable for use in surgical procedures that demand an especially high degree of viscosity and rapid adhesive performance.
Luo, Zhen; Cao, Qixin
2017-01-01
Previous meta-analyses have been conducted to compare the efficacy of fibrin glue (FG) versus sutures in pterygium surgery; however, additional clinical trials have since been published. Therefore, we conducted an updated meta-analysis to further explore the association between FG application in pterygium surgery, and the recurrence rate, complication rate, and surgical duration. An electronic literature search for eligible studies published before July 29, 2016 was conducted across multiple databases. Odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CI) were calculated. Publication bias of the included articles was evaluated by funnel plots. Differences in recurrence rate and complication rate between the FG and suture groups were evaluated in terms of OR with 95% CI, and SMD with 95% CI were used to estimate the difference in surgical duration. Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Twenty-four studies were included in this study. The pooled ORs for recurrence rate and complication rate were 0.35 and 1.121, respectively. The pooled SMD for surgical duration was −4.142. The TSA results indicated that evidence of the effect was sufficient in the recurrence group and surgical duration group. Although there was no difference in complication rate between FG and sutures, the apparent advantages of FG over sutures are shorter surgical duration and greater reduction in the recurrence rate of pterygium. PMID:28489563
In vivo near infrared (NIRS) sensor attachment using fibrin bioadhesive
NASA Astrophysics Data System (ADS)
Macnab, Andrew; Pagano, Roberto; Kwon, Brian; Dumont, Guy; Shadgan, Babak
2018-02-01
Background: `Tisseel' (Baxter Healthcare, Deerfield, IL) is a fibrin-based sealant that is commonly used during spine surgery to augment dural repairs. We wish to intra-operatively secure a near infrared spectroscopy (NIRS) sensor to the dura in order to monitor the tissue hemodynamics of the underlying spinal cord. To determine if `Tisseel' sealant adversely attenuates NIR photon transmission. Methods: We investigated `Tisseel' in both an in vitro and in vivo paradigm. For in vitro testing, we used a 1 mm pathlength cuvette containing either air or `Tisseel' interposed between a NIR light source (760 and 850 nm) and a photodiode detector and compared transmittance. For in vivo testing, a continuous wave (760 and 850 nm) spatiallyresolved NIRS device was placed over the triceps muscle using either conventional skin apposition (overlying adhesive bandage) or bioadhesion with `Tisseel'. Raw optical data and tissue saturation index (TSI%) collected at rest were compared. Results: In-vitro NIR light absorption by `Tisseel' was very high, with transmittance reduced by 95% compared to air. In-vivo muscle TSI% values were 80% with conventional attachment and 20% using fibrin glue. Conclusion: The optical properties of `Tisseel' significantly attenuate NIR light during in-vitro transmittance and critically compromise photon transmission in-vivo.
[Anal fissure of cryptoglandular origin. Therapeutic options].
Casal, Enrique; de San Ildefonso, Alberto; Sánchez, Juan; Facal, Cristina; Pampin, José
2005-12-01
Anal fistula is a frequent condition. The most commonly accepted origin is infectious. The most widely used classification is based on cryptoglandular theory and on the position of the fistulous tract in relation to the anal sphincter. Physical examination will help to identify the type of fistula and allow its treatment to be planned. The most widely used complementary tests are endoanal ultrasound and magnetic resonance imaging. We review the various therapeutic options and their results, especially fistulotomy, endorectal advancement flap, use of sedal, anodermal advancement flap, sphincterorrhaphy with sphincter repair, and fibrin glue.
Successful human long-term application of in situ bone tissue engineering
Horch, Raymund E; Beier, Justus P; Kneser, Ulrich; Arkudas, Andreas
2014-01-01
Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor-site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β-tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto-transplanted bone marrow aspirate from the iliac crest. The following post-operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio-venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain-free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor-site defect utilizing TE and RM techniques in human patients with long-term stability. PMID:24801710
Controlling air leaks using free pericardial fat pads as surgical sealant in pulmonary resection.
Ikeda, Takeshi; Sasaki, Masato; Yamada, Narihisa; Takamori, Atsushi; Tanabe, Sawaka; Okada, Akitoshi; Sakon, Kayo; Mizunaga, Tae; Koshiji, Takaaki
2015-04-01
This study evaluated the feasibility and efficacy of a new operative method for controlling intraoperative air leaks using free pericardial fat pads as a covering sealant in pulmonary resection. To manage air leaks that must be controlled in pulmonary resection at the first water sealing test, collected free pericardial fat was used as a covering sealant and sewn on by the suture closing the lesion. In cases of uncontrolled air leaks at the second sealing test, fibrin glue was used to fill the residual lesion between the fat and visceral pleura. Fifty-one eligible patients were enrolled in this study to evaluate the duration of postoperative air leaks and the condition of the implanted fat on chest computed tomography (CT) 6 months later. The mean duration of postoperative air leaks was 1.05 ± 1.84 days in the 39 cases that received the pericardial fat covering technique only and 2.66 ± 3.42 days in the 12 cases that received the pericardial fat covering technique combined with fibrin glue. Prolonged alveolar air leaks occurred in 1 case and 2 cases, respectively. No cases required conversion to conventional methods, and there were no further adverse events. On follow-up chest CT approximately 62.7% of obvious engrafted fat survived. Using free pericardial fat pads as a sealant to control air leaks in pulmonary resection is safe and has good feasibility and potent efficacy. This new method can be an innovative technique for preventing prolonged air leaks. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Omitting chest tube drainage after thoracoscopic major lung resection.
Ueda, Kazuhiro; Hayashi, Masataro; Tanaka, Toshiki; Hamano, Kimikazu
2013-08-01
Absorbable mesh and fibrin glue applied to prevent alveolar air leakage contribute to reducing the length of chest tube drainage, length of hospitalization and the rate of pulmonary complications. This study investigated the feasibility of omitting chest tube drainage in selected patients undergoing thoracoscopic major lung resection. Intraoperative air leakages were sealed with fibrin glue and absorbable mesh in patients undergoing thoracoscopic major lung resection. The chest tube was removed just after tracheal extubation if no air leakages were detected in a suction-induced air leakage test, which is an original technique to confirm pneumostasis. Patients with bleeding tendency or extensive thoracic adhesions were excluded. Chest tube drainage was omitted in 29 (58%) of 50 eligible patients and was used in 21 (42%) on the basis of suction-induced air leakage test results. Male gender and compromised pulmonary function were significantly associated with the failure to omit chest tube drainage (both, P < 0.05). Regardless of omitting the chest tube drainage, there were no adverse events during hospitalization, such as subcutaneous emphysema, pneumothorax, pleural effusion or haemothorax, requiring subsequent drainage. Furthermore, there was no prolonged air leakage in any patients: The mean length of chest tube drainage was only 0.9 days. Omitting the chest tube drainage was associated with reduced pain on the day of the operation (P = 0.046). The refined strategy for pneumostasis allowed the omission of chest tube drainage in the majority of patients undergoing thoracoscopic major lung resection without increasing the risk of adverse events, which may contribute to a fast-track surgery.
Development of a fast curing tissue adhesive for meniscus tear repair.
Bochyńska, Agnieszka Izabela; Hannink, Gerjon; Janssen, Dennis; Buma, Pieter; Grijpma, Dirk W
2017-01-01
Isocyanate-terminated adhesive amphiphilic block copolymers are attractive materials to treat meniscus tears due to their tuneable mechanical properties and good adhesive characteristics. However, a drawback of this class of materials is their relatively long curing time. In this study, we evaluate the use of an amine cross-linker and addition of catalysts as two strategies to accelerate the curing rates of a recently developed biodegradable reactive isocyanate-terminated hyper-branched adhesive block copolymer prepared from polyethylene glycol (PEG), trimethylene carbonate, citric acid and hexamethylene diisocyanate. The curing kinetics of the hyper-branched adhesive alone and in combination with different concentrations of spermidine solutions, and after addition of 2,2-dimorpholinodiethylether (DMDEE) or 1,4-diazabicyclo [2.2.2] octane (DABCO) were determined using FTIR. Additionally, lap-shear adhesion tests using all compositions at various time points were performed. The two most promising compositions of the fast curing adhesives were evaluated in a meniscus bucket handle lesion model and their performance was compared with that of fibrin glue. The results showed that addition of both spermidine and catalysts to the adhesive copolymer can accelerate the curing rate and that firm adhesion can already be achieved after 2 h. The adhesive strength to meniscus tissue of 3.2-3.7 N was considerably higher for the newly developed compositions than for fibrin glue (0.3 N). The proposed combination of an adhesive component and a cross-linking component or catalyst is a promising way to accelerate curing rates of isocyanate-terminated tissue adhesives.
Use of a fibrin adhesive for conjunctival closure in trabeculectomy.
Martinez-de-la-Casa, José M; Rayward, Omar; Saenz-Frances, Federico; Mendez, Carmen; Bueso, Enrique Santos; Garcia-Feijoo, Julián
2013-08-01
To assess the safety and efficacy of a fibrin tissue adhesive (Tissucol Duo(®) ) used to close the conjunctiva in trabeculectomy. A nonrandomized prospective study including 57 patients with chronic simple glaucoma who underwent trabeculectomy surgery. All the trabeculectomies were conducted by the same surgeon using the same surgical technique with the exception that conjunctival closure was achieved by either running Nylon 10/0 suture (n = 29) or using the fibrin glue (n = 28). Preoperative and postoperative data were obtained on intraocular pressure (IOP), number of hypotensive medications used, self-reported discomfort and complications arising during and after surgery. No differences were detected between the two patient groups regarding the intraocular pressure reduction achieved during follow-up. In the first 2 weeks of follow-up, reported discomfort assessed using a visual analogue scale was significantly lower in the Tissucol Duo(®) group. Two patients in the Tissucol Duo(®) group suffered conjunctival dehiscence and suturing was required at 24 hours postsurgery. Remaining complications were similar in the two groups. The use of Tissucol Duo(®) seems to be a safe and efficient option for conjunctival closure in trabeculectomy that simplifies the surgical procedure and reduces patient discomfort in the immediate postoperative period. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.
Ito, Kiyoshi; Aoyama, Tatsuro; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro
2015-12-01
The nonpenetrating titanium clip has been successfully used in peripheral arterial bypass surgery. The purpose of this study was to evaluate the leakage pressures and patterns of nonpenetrating titanium clips using a simple model that mimicked spinal surgery. In addition, the authors describe their surgical experience with these clips and the follow-up results in 31 consecutive patients. The authors compared nonpenetrating titanium clips and expanded polytetrafluoroethylene (ePTFE) sutures in relation to the water pressure that could be tolerated by sutured ePTFE sheets, and the leakage pressure patterns were determined. The changes in leakage pressures at 5 minutes, 30 minutes, and 12 hours were examined when the clips and sutures were used in combination with the mesh-and-glue technique in an in vitro study. Thirty-one patients underwent spinal intradural procedures using nonpenetrating titanium clips to suture the dura maters using the meshand-glue technique, involving fibrin glue and polyglycolic acid-fibrin sheets. A significant difference was apparent between the ePTFE suture group and the nonpenetrating titanium clip group, with the latter showing a leakage pressure that could be sustained and was 1508% higher than that of the former (p = 0.001). In relation to leakage patterns, the nonpenetrating titanium clips did not make any suture holes in the ePTFE sheet and fluid leakage occurred between the clips, whereas fluid leakage was associated with the pressure elevation that occurred at the suture holes made by the ePTFE sutures. Of the 31 patients who underwent spinal intradural procedures using nonpenetrating titanium clips, 1 (3.2%) experienced cerebrospinal fluid (CSF) leakage postoperatively. No other complications-for example, allergic reactions, adhesions, or infections--were encountered. The interrupted placement of nonpenetrating titanium clips enables dural closure without creating any holes. These clips facilitate improvements in the initial leakage pressure and reduce postoperative CSF leakage following spinal surgery. The authors conclude that it is very beneficial to suture the spinal dura mater using nonpenetrating titanium clips given the anatomical characteristics of the spinal dura mater and the fact that the clips do not create suture holes.
Enterocutaneous fistula: are treatments improving?
Draus, John M; Huss, Sara A; Harty, Niall J; Cheadle, William G; Larson, Gerald M
2006-10-01
We studied the etiology, treatment, and outcome of enterocutaneous fistulas in 106 patients to evaluate our current practice and the impact of newer therapies-octreotide, wound vacuum-assisted closure (VAC), and fibrin glue-on clinical outcomes. Review of the literature and our own 1990 study indicate a mortality rate of 5% to 20% for enterocutaneous fistula, and a healing rate of 75% to 85% after definitive surgery. We reviewed all cases of gastrointestinal-cutaneous fistula from 1997 to 2005 at 2 large teaching hospitals. We identified 106 patients with enterocutaneous fistula; patients with irritable bowel disease and anorectal fistulas were excluded. The origin of the fistula was the small bowel in 67 patients, colon in 26, stomach in 8, and duodenum in 5. The etiology of the fistula was previous operation in 81 patients, trauma in 15, hernia mesh erosion in 6, diverticulitis in 2, and radiation in 2. Of the 106 patients in the study, 31 had a high output fistula (greater than 200 mL/day), 44 had a low output fistula, and, in 31 patients, the fistula output was low but there was no record of volume. Initial treatment was nonoperative except for patients with an abscess who needed urgent drainage. In 24 patients, the effect of octreotide was monitored: in 8 patients, fistula output declined; in 16 patients, octreotide was of no benefit. Fibrin glue was used in 8 patients and was of benefit to 1. The wound VAC was used in 13 patients: 12 patients still required operative repair of the fistula, whereas the fistula was healed in 1 patient. The main benefit of the VAC system was improved wound care in all patients before definitive surgery. Total parenteral nutrition was used in most patients to provide nutritional support. Operative repair was performed in 77 patients and was successful in 69 (89%), failing in 6 patients with persistent cancer or infection. Nonoperative treatment was used in 29 patients and resulted in healing in 60%. Of 106 patients, 7 (7%) died of fistula complications. The cause of death was persistence or recurrence of cancer in 4 patients and persistent sepsis in 3. Enterocutaneous fistula continues to be a serious surgical problem. The wound VAC and fibrin glue had anecdotal successes (n = 2), and one-third of patients responded to octreotide. We believe that octreotide should be tried in most patients and that the wound VAC has a role in selected patients. Although 7% overall mortality is lower than in previous studies, the number managed without operation (27%) remains the same. In addition to early control of sepsis, nutritional support, and wound care, a well-timed operation was the most effective treatment.
Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold?
Kim, Yong Sang; Choi, Yun Jin; Suh, Dong Suk; Heo, Dong Beom; Kim, Yong Il; Ryu, Jae-Sung; Koh, Yong Gon
2015-01-01
The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions. To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold. Cohort study; Level of evidence, 3. This study retrospectively evaluated 54 patients (56 knees) who were examined with second-look arthroscopy after MSC implantation for cartilage lesions in their OA knees. Patients were divided into 2 groups: 37 patients (39 knees) were treated with MSC implantation without a scaffold (group 1), and 17 patients (17 knees) underwent implantation of MSCs loaded in fibrin glue as a scaffold (group 2). Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed with the International Cartilage Repair Society (ICRS) grade. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes. At final follow-up (mean, 28.6 months; range, 24-34 months), the mean IKDC score and Tegner activity scale in each group significantly improved: group 1, from 38.1±7.7 to 62.0±11.7 (IKDC) and from 2.5±0.9 to 3.5±0.8 (Tegner); group 2, from 36.1±6.2 to 64.4±11.5 (IKDC) and from 2.2±0.8 to 3.8±0.8 (Tegner) (P<.001 for all). According to the overall ICRS cartilage repair grades, 9 of the 39 lesions (23%) in group 1 and 12 of the 17 lesions (58%) in group 2 achieved a grade of I or II. There was a significant difference in ICRS grades between the groups (P=.028). Overweight (body mass index≥27.5 kg/m2) and large lesion size (≥5.7 cm2) were significant predictors of poor clinical and arthroscopic outcomes in group 1 (P<.05 for both). There was a similar trend in group 2, but the differences were not significant, possibly owing to the smaller sample size. Clinical and arthroscopic outcomes of MSC implantation were encouraging for OA knees in both groups, although there were no significant differences in outcome scores between groups. However, at second-look arthroscopy, there were better ICRS grades in group 2. © 2014 The Author(s).
Cao, Wen; Chang, Ya-Fei; Zhao, Ai-Chao; Chen, Bang-Dang; Liu, Fen; Ma, Yi-Tong; Ma, Xiang
2017-08-01
The present study aimed to investigate the protective effects of rAAV9-CyclinA2 combined with fibrin glue (FG) in vivo in rats after myocardial infarction (MI). Ninety male Sprague-Dawley rats were randomized into 6 groups (15 in each group): sham, MI, rAAV9-green fluorescent protein (GFP) + MI, rAAV9-CyclinA2 + MI, FG + MI, and rAAV9-CyclinA2 + FG + MI. Packed virus (5 × 10 11 vg/ml) in 150 µl of normal saline or FG was injected into the infarcted myocardium at five locations in rAAV9-GFP + MI, rAAV9-CyclinA2 + MI, and rAAV9-CyclinA2 + FG + MI groups. The sham, MI, and FG + MI groups were injected with an equal volume of normal saline or FG at the same sites. Five weeks after injection, echocardiography was performed to evaluate the left ventricular function. The expressions of CyclinA2, proliferating cell nuclear antigen (PCNA), and phospho-histone-H3 (H3P), vascular density, and infarct area were assessed by Western blot, immunohistochemistry, immunofluorescence, and Masson staining. As a result, the combination of rAAV9-CyclinA2 and FG increased ejection fraction and fractional shortening compared with FG or rAAV9-CyclinA2 alone. The expression level of CyclinA2 was significantly higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI and FG + MI groups (70.1 ± 1.86% vs. 14.74 ± 2.02%, P < 0.01; or vs. 50.13 ± 3.80%; P < 0.01). A higher expression level of PCNA and H3P was found in the rAAV9-CyclinA2 + FG + MI group compared with other groups. Comparing with other experiment groups, collagen deposition and the infarct size significantly decreased in rAAV9-CyclinA2 + Fibrin + MI group. The vascular density was much higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI group. We concluded that fibrin glue combined with rAAV9-CyclinA2 was found to be effective in cardiac remodeling and improving myocardial protection.
A different type of 'glue ear': report of an unusual case of prominent ears.
Purcell, Elizabeth M; O'Neill, Ann C; Regan, Padraic J
2003-09-01
Prominent ears is a condition that can cause extreme psychological distress in young people. This cosmetic deformity can be corrected by otoplasty, an outpatient surgical procedure that is associated with a high rate of patient satisfaction. We report the unusual case of a teenage boy who had repeatedly applied cyanoacrylate adhesive ("superglue") to his postauricular skin in an attempt to pin back his prominent ears. This case of "glue ear" was ultimately resolved by successful otoplasty, although the residual effects of the glue resulted in delayed healing of the surgical wound.
Stafford, Giles H; Bunn, Jonathan R; Villar, Richard N
2011-01-01
We describe one- to three-year results of a novel use of fibrin glue in the treatment of cartilage damage by arthroscopy in the hip. This technique uses the microfracture technique and fibrin adhesive to bond delaminated articular cartilage to the underlying subchondral bone. This is generally performed in conjunction with treatment of underlying pathology such as femoroacetabular impingement. Patients were assessed using the modified Harris Hip Score (MHHS) pre- and post-operatively, and statistical significance determined by Student's t-test. We report the mid-term results of 43 patients with femoroacetabular impingement who have undergone this technique for re-attachment of delaminated chondral flaps. There was a statistically significant improvement in MHHS at a mean of 28 months (16 to 42 months) after surgery (p<0.0001). The MHHS for pain improved significantly from 21.8 (95% CI 19.0 to 24.7) pre-operatively to 35.8 (95% CI 32.6 to 38.9) post-operatively (p<0.0001). The MHHS for function also showed significant, although more modest, improvements from 40.0 (95% CI 37.7 to 42.3) pre-operatively to 43.6 (95% CI 41.4 to 45.8) post-operatively (p=0.0006). There were three patients who had early (within 12 months of the index procedure) revision arthroscopy for iliopsoas pathology. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive is a useful technique in the treatment of early cartilage damage. We have seen encouraging mid-term results, although further studies are warranted.
Chronic, otogenic, epidural pneumatocoele with delayed mass effect: case report.
Barbieri, F; Fiorino, F
2010-05-01
Mastoid hyperpneumatisation predisposes to intracranial pneumatocoele development, due to the risk of rupture of the thin, bony walls. Intracranial pneumatocoele may be precipitated by even minor head trauma or an abrupt change in middle-ear pressure, with the potential risk of infectious or compressive intracranial complications. A 19-year-old man with mastoid hyperpneumatisation developed a chronic intracranial-epidural pneumatocoele of traumatic origin in the right parieto-occipital area, in contiguity with the posterior mastoid cells. Eighteen months later, after a common cold, the patient developed signs of intracranial hypertension, due to the pneumatocoele spreading to the right epidural anterior fossa. A large right mastoidectomy extended to the retrosigmoid cells was performed, and a watertight seal applied over a large retrosigmoid cell using bovine pericardium and a mixture of bone powder and fibrin glue. The patient was discharged on post-operative day three with no symptoms. Ten days after surgery, computed tomography monitoring showed complete reabsorption of the pneumatocoele. In cases of chronic, otogenic, epidural pneumatocoele, the possibility of the sudden onset of serious complications suggests the need for early repair of the communication between the temporal bone and the intracranial compartments. Closure of the fistula using autogenic and/or allogenic materials is usually adequate to resolve the pneumatocoele.
Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.
Cheng, Yao; Ye, Mingxin; Xiong, Xianze; Peng, Su; Wu, Hong Mei; Cheng, Nansheng; Gong, Jianping
2016-02-15
Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. We searched The Cochrane Library (2015, Issue 7), MEDLINE (1946 to 26 August 2015), EMBASE (1980 to 26 August 2015), Science Citation Index Expanded (1900 to 26 August 2015), and Chinese Biomedical Literature Database (CBM) (1978 to 26 August 2015). We included all randomized controlled trials that compared fibrin sealant group (fibrin glue or fibrin sealant patch) versus control group (no fibrin sealant or placebo) in people undergoing pancreatic surgery. Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). We included nine trials involving 1095 participants who were randomized to the fibrin sealant group (N = 550) and the control group (N = 545) after pancreatic surgery. All of the trials were at high risk of bias. There was no evidence of differences in overall postoperative pancreatic fistula (fibrin sealant 29.6%; control 31.0%; RR 0.93, 95% CI 0.71 to 1.21; P = 0.58; nine studies; low-quality evidence), postoperative mortality (3.1% versus 2.1%; Peto OR 1.29, 95% CI 0.59 to 2.82; P = 0.53; eight studies; very low-quality evidence), overall postoperative morbidity (29.6% versus 28.9%; RR 1.04, 95% CI 0.82 to 1.32; P = 0.77; five studies), reoperation rate (8.7% versus 10.7%; RR 0.80, 95% CI 0.53 to 1.21; P = 0.29; five studies), or length of hospital stay (12.9 days versus 13.1 days; MD -0.73 days, 95% CI -2.20 to 0.74; P = 0.331; six studies) between the groups. The proportion of postoperative pancreatic fistula that was clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was inadequate evidence to establish the effect of fibrin sealants on clinically significant postoperative pancreatic fistula (9.4% versus 13.4%; RR 0.72, 95% CI 0.42 to 1.21; P = 0.21; three studies). Quality of life and cost effectiveness were not reported in any of the trials. Based on the current available evidence, fibrin sealants do not seem to prevent postoperative pancreatic fistula in people undergoing pancreatic surgery.
Terasaka, Shunsuke; Taoka, Toshiaki; Kuroda, Satoshi; Mikuni, Nobutaka; Nishi, Toru; Nakase, Hiroyuki; Fujii, Yukihiko; Hayashi, Yasuhiko; Murata, Jun-Ichi; Kikuta, Ken-Ichiro; Kuroiwa, Toshihiko; Shimokawa, Sachie; Houkin, Kiyohiro
2017-05-01
The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm 2 to <100 cm 2 . Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm 2 . To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure.
Successful human long-term application of in situ bone tissue engineering.
Horch, Raymund E; Beier, Justus P; Kneser, Ulrich; Arkudas, Andreas
2014-07-01
Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor-site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β-tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto-transplanted bone marrow aspirate from the iliac crest. The following post-operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio-venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain-free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor-site defect utilizing TE and RM techniques in human patients with long-term stability. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Campos, Josemberg Marins; Pereira, Eduardo Franca; Evangelista, Luis Fernando; Siqueira, Luciana; Neto, Manoel Galvão; Dib, Victor; Falcão, Marcelo; Arantes, Vitor; Awruch, Diego; Albuquerque, Walton; Ettinger, João; Ramos, Almino; Ferraz, Álvaro
2011-10-01
Gastrobronchial fistula (GBF) is a serious complication following bariatric surgery, whose treatment by thoracotomy and/or laparotomy involves a high morbidity rate. We present the outcomes of endoscopic management for GBF as a helpful technique for its healing process. This is a multicenter retrospective study of 15 patients who underwent gastric bypass (n = 10) and sleeve gastrectomy (n = 5) and presented GBF postoperatively (mean of 6.7 months). Ten patients developed lung abscess and were treated by antibiotic therapy (n = 10) and thoracotomy (n = 3). Abdominal reoperation was performed in nine patients for abscess drainage (n = 9) and/or ring removal (n = 4) and/or nutritional access (n = 6). The source of the GBF was at the angle of His (n = 14). Furthermore, 14 patients presented a narrowing of the gastric pouch treated by 20 or 30 mm aggressive balloon dilation (n = 11), stricturotomy or septoplasty (n = 10) and/or stent (n = 7). Fibrin glue was used in one patient. We performed, on average, 4.5 endoscopic sessions per patient. Endotherapy led to a 93.3% (14 out of 15) success rate in GBF closure with an average healing time of 4.4 months (range, 1-10 months), being shorter in the stent group (2.5 × 9.5 months). There was no recurrence during the average 27.3-month follow-up. A patient persisted with GBF, despite the fibrin glue application, and decided to discontinue it. GBF is a highly morbid complication, which usually arises late in the postoperative period. Endotherapy through different strategies is a highly effective therapeutic option and should be implemented early in order to shorten leakage healing time.
Technical Modifications for Intraoral Quadrangular Le Fort II Osteotomy.
Klug, Clemens; Cede, Julia
2017-02-01
The intraoral quadrangular Le Fort II osteotomy (IQLFIIO) represents a reliable surgical method in cases of midfacial deficiency with good functional, esthetic, and stable long-term results. In this technical note, we present 3 surgical modifications to previous reports: 1) inferior orbital rim osteotomy by angulated piezosurgical instruments, thereby avoiding the use of chisels in the orbital region; 2) osteosynthetic fixation only laterally at the zygomatic buttress with 2 L-shaped miniplates, thus avoiding paranasal osteosynthesis; and 3) advancement step camouflage in the lateral infraorbital region with a compound mass of autologous bone chips and fibrin glue with the intention to reduce bone block-associated side effects. Thirteen consecutive patients presenting with midfacial deficiency and Class III malocclusion were treated by IQLFIIO and mandibular osteotomy. In all cases, osteotomy and consecutive down fracture could be conducted as planned using the piezotome. No atypical fractures were encountered. No cases of infraorbital nerve anesthesia developed. Midfacial hypesthesia was found in 54% of the operated sides after 3 months, in 23% after 6 months, and in 13% after 12 months. The 5-month postoperative 3-dimensional scans revealed osseous healing at the infraorbital advancement step. Our results suggest that IQLFIIO can be conducted fully without chisels in the orbital region. Implementation of piezosurgery in IQLFIIO allows for safe bone cutting in the orbital region. Two miniplates and step camouflage with fibrin glue-stabilized bone chips were sufficient for osseous healing. Future studies will focus on quantitative soft to hard tissue changes that occur with IQLFIIO advancement. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Zong, Jian-Chun; Mosca, Michael J; Degen, Ryan M; Lebaschi, Amir; Carballo, Camila; Carbone, Andrew; Cong, Guang-Ting; Ying, Liang; Deng, Xiang-Hua; Rodeo, Scott A
2017-04-01
Bone marrow aspirate has been used in recent years to augment tendon-to-bone healing, including in rotator cuff repair. However, the healing mechanism in cell-based therapy has not been elucidated in detail. Sixteen athymic nude rats were randomly allocated to 2 groups: experimental (human mesenchymal stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing enthesis. Macrophages were identified using CD68 and CD163 staining, and proliferating cells were identified using proliferating cell nuclear antigen staining. More organized and stronger staining for collagen II and a higher abundance of SOX9 + cells were observed at the enthesis in the experimental group at 2 weeks. There was significantly higher Gli1 and Patched1 expression in the experimental group at the enthesis at 2 weeks and higher numbers of Ihh + cells in the enthesis of the experimental group vs control at both 2 weeks and 4 weeks postoperatively. There were more CD68 + cells localized to the tendon midsubstance at 2 weeks compared with 4 weeks, and there was a higher level of CD163 staining in the tendon midsubstance in the experimental group than in the control group at 4 weeks. Stem cell application had a positive effect on fibrocartilage formation at the healing rotator cuff repair site. Both SOX9 and Ihh signaling appear to play an important role in the healing process. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Comparative analysis of conventional and biological treatment in healing of bone disease.
Guo, Wen-Zhe; Di, Hui; Chu, Guo-Hua; Lu, Lu
2018-01-01
The healing of Bone tissue consists of a complex process. Hence, we designed our study to evaluate chondrial diseases, which are as they have a very low healing capacity. Seventy two elderly osteoarthritis (OA) and 54-paediatric juvenile idiopathic arthritis (JIA) patients were included. The group was divided as 24 OA patients and 18 JIA patients in each group. Group I received Hyualuronic acid and glucocorticoides. Group II received platelet rich plasma and fibrin glue. Group III received PRP, fibrin glue, and MSC. 40 control patients received only PRP treatment. Out of 72 OA patients 35 (48.6%) male and 37 (51.4%) female with mean age of 48 ± 6.5 years. 64 (88.9%) Patients had pain and swelling. 52 (72.2%) lacked flexibility. 42 (58.3%) had hypertrophy. 28 (38.9%) had less cartilage thickness. 34 (47.2%) were in grade 3, grade 2 has 28 (38.9%) and grade 1 has 10 (13.9%) patients respectively. Among 54 JIA patients 28 (51.9%) male and 26 (48.1%) female patients with mean, age 4.6 ± 3.8 years. 39 (72.2%) had pain and swelling. 32 (59.3%) lacked flexibility. 29 (53.7%) children's had functional disability. Group I patients showed 30% improvement with no statistical significance (P < 0.21). Group II showed 45% improvement with statistical significance (P < 0.01). In Group III 80%, improvement was observed with statistical significance (P < 0.001). In 40 control patients, 60% improvement was observed. In conclusion, use of these MSC, PRP, and PPP are safe and less cost effective for treating OA and JIA.
Biomaterials in the treatment of anal fistula: hope or hype?
Scoglio, Daniele; Walker, Avery S; Fichera, Alessandro
2014-12-01
Anal fistula (AF) presents a chronic problem for patients and colorectal surgeons alike. Surgical treatment may result in impairment of continence and long-term risk of recurrence. Treatment options for AFs vary according to their location and complexity. The ideal approach should result in low recurrence rates and minimal impact on continence. New technical approaches involving biologically derived products such as biological mesh, fibrin glue, fistula plug, and stem cells have been applied in the treatment of AF to improve outcomes and decrease recurrence rates and the risk of fecal incontinence. In this review, we will highlight the current evidence and describe our personal experience with these novel approaches.
Schantz, Jan-Thorsten; Brandwood, Arthur; Hutmacher, Dietmar Werner; Khor, Hwei Ling; Bittner, Katharina
2005-09-01
Biomimetic scaffolds offer great potentials in the development of bone analogs for tissue engineering. The studies presented in this paper focus specifically on the osteogenic potential of the novel PCL/CaP matrices and its degradation behavior. Biodegradable Polymer-ceramic Scaffolds were fabricated using the solid free form fabrication technology: Fused Deposition Modeling (FDM). The scaffold architecture was characterized by a honeycomb-like design and a complete interconnectivity of the pores. Human mesenchymal stem cells (MSCs) were seeded together with fibrin glue into PCL/CaP scaffolds and cultured in vitro for periods of up to eight weeks. Cellular adhesion, proliferation and osteogenic differentiation were assessed in these constructs using a range of histological and microscopic techniques. In additional experiments, degradation was assessed by measuring mass loss, diameter change, molecular weight change and by scanning electron micrographs. MSCs were able to adhere, migrate, and differentiate along the osteogenic lineage with in these scaffolds. The PCL/CaP scaffolds showed up to 27 fold increased degradation of compared to PCL scaffolds.
Successful embolization of iatrogenic ruptured coronary artery using Onyx: a new technique.
Asouhidou, I; Katsaridis, V
2014-12-01
Iatrogenic perforation of coronary artery is rare during percutaneous coronary intervention (PCI); however the complications are life-threatening. Patients in this clinical setting may be treated either by stent placement, closure of the perforation with fibrin glue or coils, or with emergency bypass surgery. Onyx, a new material that has been used successfully in cerebral arteries, represents a new and safe alternative. The advantage of Onyx is that it is easily injected through a microcatheter and it allows for a longer injection time having also the ability to reach difficult anatomical locations. We present the first case of successful embolization of a right coronary artery perforation during coronary angiography using Onyx.
New generation tissue sealants and hemostatic agents: innovative urologic applications.
Traver, Michael A; Assimos, Dean G
2006-01-01
Control of blood loss during urologic surgery is paramount to the success of patient recovery. Hemostatic agents and tissue sealants are used routinely to prevent excess blood loss and in reconstruction during surgical repair. Some of the available products include thrombin sealant, fibrin glue, bovine serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in mechanism, cost, and application. Complications can include allergic reactions or thromboembolism and the risk of contracting bovine spongiform encephalitis or hepatitis. Many new hemostatic agents are being developed and approved. The benefits and risks of use of these agents versus conventional treatment need to be considered on a case-by-case basis by the surgeon.
Biomaterials in the Treatment of Anal Fistula: Hope or Hype?
Scoglio, Daniele; Walker, Avery S.; Fichera, Alessandro
2014-01-01
Anal fistula (AF) presents a chronic problem for patients and colorectal surgeons alike. Surgical treatment may result in impairment of continence and long-term risk of recurrence. Treatment options for AFs vary according to their location and complexity. The ideal approach should result in low recurrence rates and minimal impact on continence. New technical approaches involving biologically derived products such as biological mesh, fibrin glue, fistula plug, and stem cells have been applied in the treatment of AF to improve outcomes and decrease recurrence rates and the risk of fecal incontinence. In this review, we will highlight the current evidence and describe our personal experience with these novel approaches. PMID:25435826
[Local fixation of antibiotics by fibrin spray : In bone defects with soft tissue involvement].
Janko, Maren; Nau, Christoph; Marzi, Ingo; Frank, Johannes
2017-02-01
In acute and chronic bone infections with concomitant soft tissue involvement the current gold standard is radical surgical debridement including explantation of the infected prosthetic devices. This is followed by initiation of systemic antibiotic therapy appropriate for the antibiogram. Several revision operations are often necessary to achieve complete healing. Additional treatment with local antibiotics or antibiotic-containing substances is routinely used in bone surgery. Apart from the typical procedures with commercially available products, we have conducted a study with 21 patients by application of local antibiotic treatment in combination with the fibrin glue spray technique and evaluated the results. Out of nine wounds of the lower extremities with bone involvement, total healing could be achieved in eight cases. We were also successful in two out of three very complex pelvic wounds; however, as expected the implant infections were complicated. Out of the seven desolate cases we were only able to achieve complete long-term healing in two cases. In the meantime we routinely use the described method in such special disastrous infection situations; however, this is carried out only in combination with established surgical procedures in sepsis surgery and anti-infection management.
Topical tissue plasminogen activator appears ineffective for the clearance of intraocular fibrin.
Zwaan, J; Latimer, W B
1998-06-01
To determine the efficacy of topical tissue plasminogen activator (tPA) for the resolution of postoperative or inflammatory intraocular fibrinous exudates. Each treatment consisted of drops of 1 mg/ml tPA given 9 times 5 minutes apart. Records were reviewed and the results at 24 and 48 hours were recorded. Sixty-two patients had a total of 94 treatments. Fibrin exudates following intraocular surgery in 34 patients were treated 44 times. In 6 patients there was a positive result. Fibrin associated with intraocular infection was treated in 9 patients. None showed clear improvement. Nineteen patients had a total of 34 treatments for poorly controlled intraocular pressure (IOP) after glaucoma surgery. Five patients showed adequate control of the IOP, 12 did not change, and 2 had a questionable improvement. Eleven patients had adequate IOP control after additional treatment. Seven required suture lysis, 2 ab interno bleb revision, and 2 YAG capsulotomy or iridotomy to reduce the IOP to an acceptable level. Within the limits of this retrospective study and taking into account that fibrin may resolve spontaneously, it appears that topical tPA drops are not effective for the liquefaction of intraocular fibrin after surgery or in association with intraocular inflammation. They did not improve IOP control after glaucoma surgery.
Optimization of Fibrin Glue Spray Systems for Ophthalmic Surgery
Chaurasia, Shyam S.; Champakalakshmi, Ravi; Angunawela, Romesh I.; Tan, Donald T.; Mehta, Jodhbir S.
2012-01-01
Purpose To optimize fibrin glue (FG) spray for ophthalmic surgery using two spray applicators, EasySpray and DuploSpray systems, by varying the distance from point of application and the pressure/flow rate, and to compare the adhesive strength of sutured and sutureless (FG sprayed) conjunctival graft surgery in a rabbit model. Methods FG was sprayed on a 0.2 mm-thick sheet of paper using EasySpray by variously combining application distances of 2.5, 5, 7.5, and 10 cm with pressures of 10, 15, and 20 psi. DuploSpray was used at the same distances but with varying flow rates of 1 and 2 L/min. Subsequently, FG was sprayed on porcine corneas and FG thickness was analyzed by histology. In addition, adhesive strength of the conjunctival graft (0.5 × 0.5 cm) attached to the rabbit cornea by sutured and sutureless surgery (FG spray) was compared using a tension meter. Results Histology measurements revealed that the FG thickness decreased with increases in distance and pressure of spray using the EasySpray applicator on paper and porcine corneal sections. The adhesive strength of the sutured conjunctival graft (41 ± 4.85 [kilopascal] KPa) was found to be higher than the graft attached by spraying (10 ± 2.3 KPa) and the sequential addition of FG (6 ± 0.714 KPa). Conclusions The EasySpray applicator formed a uniform spread of FG at a distance-pressure combination of 5 cm and 20 psi. The conjunctival graft attached with sutures had higher adhesive strength compared with grafts glued with a spray applicator. Although the adhesive strength of FG applied through the applicator was similar to the drop-wise sequential technique, the former was more cost effective because more samples could be sprayed compared with the sequential manual technique. Translational Relevance The standardization of the spray system for the application of FG in ophthalmology will provide an economical method for delivering consistent healing results after surgery. PMID:24049702
Xeroradiography and ultrasonography in the evaluation of a penile injury.
Oesterling, J E; Bromberg, W D; Albertsen, P C
1986-04-01
A 34-year-old white man presented with severe penile cellulitis following injection of epoxy glue into the shaft of the penis. Preoperative xeroradiography and ultrasonography localized the hardened masses of glue to the left corpus cavernosum and subcutaneous tissues. Under the guidance of intraoperative ultrasonography this foreign material was removed surgically. Postoperatively, the cellulitis resolved promptly and xeroradiography demonstrated no residual fragments. Although various modalities, including computerized tomography and roentgenography, are available to detect foreign bodies in soft tissues, xeroradiography and ultrasonography are ideally suited for use in the male external genitalia.
Fibrin sealant use for minimising peri-operative allogeneic blood transfusion
Carless, Paul A; Henry, David A; Anthony, Danielle M
2014-01-01
Background Fibrin sealants (also referred to as biological glue or fibrin tissue adhesives) have gained increasing popularity as interventions to improve peri-operative (intra- and post-operative) haemostasis and diminish the need for allogeneic red cell transfusion (blood from an unrelated donor). Objectives To examine the efficacy of fibrin sealants in reducing peri-operative blood loss and allogeneic red blood cell (RBC) transfusion. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1950 to 2008), EMBASE (1980 to 2008), manufacturer web sites (to March 2008), and bibliographies of relevant published articles. Selection criteria Controlled trials in which adult patients scheduled for elective surgery were randomised to fibrin sealant treatment or to a control group which did not receive fibrin sealant treatment. Trials were eligible if they reported data on the number of patients exposed to allogeneic red cell transfusion, the volume of blood transfused, or blood loss (assessed objectively). Data collection and analysis The primary outcomes measured were the: number of patients exposed to allogeneic red cells, amount of blood transfused, and blood loss. Other outcomes measured were: re-operation due to bleeding, infection, mortality, thrombotic events, and length of hospital stay. Treatment effects were pooled using a random-effects model. Main results Eighteen trials that included a total of 1406 patients reported data on peri-operative exposure to allogeneic RBC transfusion. Fibrin sealant treatment, on average, reduced the rate of exposure to allogeneic RBC transfusion by a relative 37% (relative risk (RR) 0.63, 95% confidence interval (CI) 0.45 to 0.88) and 7% in absolute terms (95% CI 2% to 13%). Fourteen trials, including a total of 853 patients, provided data for post-operative blood loss. In aggregate, fibrin sealant treatment reduced blood loss on average by around 161 ml per patient (95% CI 98.25 to 224.53 ml). In the context of orthopaedic surgery, fibrin sealant treatment reduced post-operative blood loss on average by around 223 ml per patient (95% CI 119.85 to 325.18 ml) and reduced the risk of exposure to allogeneic RBC transfusion by 32% (RR 0.68, 95% CI 0.51 to 0.89). Fibrin sealant treatment was not associated with an increased risk of wound infection (RR 0.61, 95% CI 0.24 to 1.58), any infection (RR 0.93, 95% CI 0.44 to 1.94), haematoma formation (RR 0.46, 95% CI 0.18 to 1.18), or death (RR 0.85, 95% CI 0.38 to 1.89). Hospital length of stay was not reduced in patients treated with fibrin sealant (weighted mean difference (WMD) −0.21 days, 95% CI −0.42 to 0.01 days). Authors’ conclusions Overall, the results suggest that fibrin sealants are efficacious in reducing both post-operative blood loss and peri-operative exposure to allogeneic RBC transfusion. Although treatment-effect heterogeneity was observed for these primary efficacy outcomes, heterogeneity was generally in terms of the size of effect rather than the direction of effect. Fibrin sealants appeared to demonstrate their greatest beneficial effects in the context of orthopaedic surgery, where blood loss is often substantial. Trials not involving orthopaedic surgery generally showed a trend toward decreased post-operative blood loss but the observed reductions were not clinically significant. The majority of trials included in this review were small, which raises concerns about the potential effects of publication bias. Funnel plot assessment indicates that there is some evidence of publication bias in the form of a missing population of small negative trials. We believe that large, methodologically rigorous, randomised controlled trials of fibrin sealants are needed. PMID:12804501
Endoscopic treatment of tracheocele in pediatric patients.
Berlucchi, Marco; Pedruzzi, Barbara; Padoan, Rita; Nassif, Nader; Stefini, Stefania
2010-01-01
Acquired tracheal pouch known also as tracheocele is a rare air-filled diverticulum of tracheal pars membranacea. This disease may be due to esophageal or tracheal surgery, orotracheal intubation, or increased intralunimal pressure through a weak area of tracheal wall. When symptomatic and medical therapy is insufficient, this disorder must be treated surgically. Several surgical methods ranging from open neck or thoracic surgery to endoscopic managements have been reported. We report the case history of a 7-year-old boy affected by recurrent pneumonia due to tracheal pouch. The patient underwent successful brushing of tracheocele plus fibrin glue application by rigid tracheobroncoscopy. Furthermore, particular emphasis on endoscopic treatments of tracheal diverticulum is also presented. Copyright 2010 Elsevier Inc. All rights reserved.
Tamaki, Masafumi; Ikeda, Mayumi; Norimura, Naoko; Miura, Kazumasa; Yoshizawa, Kiyoshi
2012-02-01
A 61-year-old female was diagnosed as having end-stage renal failure developed dyspnea soon after introduction of continuous ambulatory peritoneal dialysis (CAPD). Chest X-ray showed a right-side massive pleural effusion. Pleuro peritoneal communication was suspicious, because the hydrothorax significantly improved by the stop of CAPD. We performed video-assisted thoracic surgery. Using indigo carmine containing peritoneal dialysis fluid through a CAPD catheter, we found a fistula on the diaphragm from which blue dialysis solution flowed out like a fountain. The fistula of the diaphragm was directly closed with a surgical stapler and covered using cellulose oxidized (Surgicel) and fibrin glue. She could restart CAPD on postoperative days 7, and no recurrence of hydrothorax has been detected for 10 months after surgical treatment.
Pathophysiology and management of spontaneous intracranial hypotension--a review.
Syed, Nadir Ali; Mirza, Farhan Arshad; Pabaney, Aqueel Hussain; Rameez-ul-Hassan
2012-01-01
Spontaneous Intracranial Hypotension is a syndrome involving reduced intracranial pressure secondary to a dural tear which occurs mostly due to connective tissue disorders such as Marfans Syndrome, and Ehler Danlos Syndrome. Patients with dural ectasias leading to CSF leakage into the subdural or epidural space classically present with orthostatic headaches and cranial nerve deficits mostly seen in cranial nerves V-VIII. Diagnosis of SIH is confirmed with the aid of neuroimaging modalities of which Cranial MR imaging is most widely used. SIH can be treated conservatively or with epidural blood patches which are now widely being used to repair dural tears, and their effectiveness is being recognized. Recently epidural injection of fibrin glue has also been used which has been found to be effective in certain patients.
Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.
Weinand, Christian; Pomerantseva, Irina; Neville, Craig M; Gupta, Rajiv; Weinberg, Eli; Madisch, Ijad; Shapiro, Frederic; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P
2006-04-01
Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.
A novel injectable tissue adhesive based on oxidized dextran and chitosan.
Balakrishnan, Biji; Soman, Dawlee; Payanam, Umashanker; Laurent, Alexandre; Labarre, Denis; Jayakrishnan, Athipettah
2017-04-15
A surgical adhesive that can be used in different surgical situations with or without sutures is a surgeons' dream and yet none has been able to fulfill many such demanding requirements. It was therefore a major challenge to develop an adhesive biomaterial that stops bleeding and bond tissues well, which at the same time is non-toxic, biocompatible and yet biodegradable, economically viable and appealing to the surgeon in terms of the simplicity of application in complex surgical situations. With this aim, we developed an in situ setting adhesive based on biopolymers such as chitosan and dextran. Dextran was oxidized using periodate to generate aldehyde functions on the biopolymer and then reacted with chitosan hydrochloride. Gelation occurred instantaneously upon mixing these components and the resulting gel showed good tissue adhesive properties with negligible cytotoxicity and minimal swelling in phosphate buffered saline (PBS). Rheology analysis confirmed the gelation process by demonstrating storage modulus having value higher than loss modulus. Adhesive strength was in the range 200-400gf/cm 2 which is about 4-5 times more than that of fibrin glue at comparable setting times. The adhesive showed burst strength in the range of 400-410mm of Hg which should make the same suitable as a sealant for controlling bleeding in many surgical situations even at high blood pressure. Efficacy of the adhesive as a hemostat was demonstrated in a rabbit liver injury model. Histological features after two weeks were comparable to that of commercially available BioGlue®. The adhesive also demonstrated its efficacy as a drug delivery vehicle. The present adhesive could function without the many toxicity and biocompatibility issues associated with such products. Though there are many tissue adhesives available in market, none are free of shortcomings. The newly developed surgical adhesive is a 2-component adhesive system based on time-tested, naturally occurring polysaccharides such as chitosan and dextran which are both biocompatible and biodegradable. Simple polymer modification has been carried out on both polysaccharides so that when aqueous solutions of both are mixed, the solutions gel in less than 10s and forms an adhesive that seals a variety of incisions. The strength of the adhesive is over 5-times the strength of commercially available Fibrin glue and is more tissue compliant than BioGlue®. This adhesive biomaterial showed excellent tissue bonding, was hemostatic, biocompatible and biodegradable. The significance of this work lies on the features of the developed tissue adhesive that it stops bleeding, bond the tissues well, can act as a drug delivery vehicle and would appeal to the surgeon in terms of the simplicity of application in complex surgical situations. There is no need for special delivery systems for application of this adhesive. The two-component adhesive can be applied one over the other using syringes. There is also no need for light curing with UV or visible light and the gelation between the two components spontaneously takes place on application leading to excellent tissue bonding. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Dong, Jingjing; Cui, Geng; Bi, Long; Li, Jie; Lei, Wei
2013-01-01
In order to improve the mechanical and biological properties of calcium phosphate cement (CPC, nanometer-biomaterial) for bone reconstruction in the rabbit femoral defect model, fibrin glue (FG, the natural product, purified from the blood) was introduced at three different ratios. The CPC powder and the FG solution were mixed, respectively, at the powder/liquid (P/L) ratios (g/mL) of 1:1, 3:1, and 5:1 (g/mL), and pure CPC was used as a control. After being implanted into the femoral defect in rabbit, the healing process was evaluated by micro-computed tomography scan, biomechanical testing, and histological examination. By micro-computed tomography analysis, the P/L ratio of 1:1 (g/mL) group indicated the largest quantity of new bone formation at 4 weeks, 8 weeks, and 12 weeks after implantation, respectively. Bone volume per trabecular volume of the 1:1 group was highest in the four groups, which was 1.45% ± 0.42%, 7.35% ± 1.45%, and 29.10% ± 1.67% at 4 weeks, 8 weeks, and 12 weeks after the operation, respectively. In the biomechanical tests, the compressive strength and the elastic modulus of the three CPC–FG groups were much higher than those of the pure CPC group at the determined time point (P < 0.05). The histological evaluation also showed the best osseointegration in the 1:1 group at 4 weeks, 8 weeks, and 12 weeks after the operation, respectively. In the 1:1 group, the bone grew into the pore of the cement in the laminar arrangement and connected with the cement tightly at the 12th week after the operation. This present study indicated that the CPC–FG composite at the P/L ratio of 1:1 (g/mL) stimulated bone regeneration better than any other designed group, which suggested that CPC–FG at the P/L ratio of 1:1 has significant potential as the bioactive material for the treatment of bone defects. PMID:23576869
Rubin, Michel Risnic; Dantas, Paulo Elias C; Nishiwaki-Dantas, M Cristina; Felberg, Sergio
2011-01-01
To compare the efficacy of conjunctival autograft surgery with the attachment to the scleral bed using fibrin tissue adhesive or mononylon 10-0 suture after resection of primary pterygium. A comparative, prospective and randomized clinical trial was performed in 47 eyes of 47 patients with primary medial located pterygium. Group 1 (adhesive) was composed by 21 patients that underwent conjunctival autograft closure with fibrin tissue adhesive (Quixil™) and Group 2 (suture) was composed by 26 patients that underwent pterygium surgery with mononylon 10-0 (Ethicon(®)) suture (suture group) after pterygium excision. All surgeries were performed by the same surgeon. Patients were assessed on the preoperative period and on the 1(st), 14(th) and 21(st) postoperative days. They were followed-up with a questionnaire of ocular discomfort and by the surgical time spent, ocular hyperemia, complications and recurrence signals, being the recurrence also evaluated at the 6th postoperative month. Data were submitted to statistical analysis. A value of p<0.005 was considered statistically significant. The average surgical time was 19.05 ± 6.12 minutes in group 1 (glue) and 48.15 ± 7.13 minutes in the group 2 (suture) (p<0.001). The ocular discomfort scale analysis showed a lower score in the 1(st) (p<0.005), 7(th) (p<0.001) and 21(th) (p<0.001) postoperative days in group 1. Ocular hyperemia was less intense in all periods of this study in group 1 (p<0.001). Complications were one in each group and both were managed with clinical treatment until the 21(th) postoperative day. There was one recurrence in group 1 and two in group 2 until the 6(th) postoperative month. In the surgical management of primary pterygium, fibrin tissue adhesive attached the conjunctival autograft, decreased the surgical time and diminished the conjunctival hyperemia and ocular discomfort with similar recurrences on the postoperative period, compared to fixation with mononylon 10.0 suture, proving to be an excellent option for conjunctival autograft attachment in primary pterygium surgery.
Dural closure for the treatment of superficial siderosis.
Egawa, Satoru; Yoshii, Toshitaka; Sakaki, Kyohei; Inose, Hiroyuki; Kato, Tsuyoshi; Kawabata, Shigenori; Tomizawa, Shoji; Okawa, Atsushi
2013-04-01
Superficial siderosis (SS) of the CNS is a rare disease caused by repeated hemorrhages in the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord leads to the progression of neurological deficits. The causes of bleeding include prior intradural surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. Recently, surgical treatment of SS associated with dural defect has been reported. The authors of the present report describe 2 surgically treated SS cases and review the literature on surgically treated SS. The patients had dural defects with fluid-filled collections in the spinal canal. In both cases, the dural defects were successfully closed, and the fluid collection was resolved postoperatively. In one case, the neurological symptoms did not progress postoperatively. In the other case, the patient had long history of SS, and the clinical manifestations partially deteriorated after surgery, despite the successful dural closure. In previously reported surgically treated cases, the dural defects were closed by sutures, patches, fibrin glue, or muscle/fat grafting. Regardless of the closing method, dural defect closure has been shown to stop CSF leakage and subarachnoid hemorrhaging. Successfully repairing the defect can halt the disease progression in most cases and may improve the symptoms that are associated with CSF hypovolemia. However, the effect of the dural closure may be limited in patients with long histories of SS because of the irreversibility of the neural tissue damage caused by hemosiderin deposition. In patients with SS, it is important to diagnose and repair the dural defect early to minimize the neurological impairments that are associated with dural defects.
Alvarez, Carlos M; Urakov, Timur M; Vanni, Steven
2018-03-01
Pseudomeningocele is a rare but well-known complication of lumbar spine surgery, which arises in 0.068%-0.1% of individuals in large series of patients undergoing laminectomy and in up to 2% of patients with postlaminectomy symptoms. In symptomatic pseudomeningoceles, surgical reexploration and repair of the dural defect are typically necessary. Whereas the goals of pseudomeningocele repair, which are extirpation of the pseudomeningocele cavity and elimination of extradural dead space, can typically be achieved by primary closure performed using nonabsorbable sutures, giant pseudomeningoceles (> 8 cm) can require more elaborate repair in which fibrin glues, dural substitute, myofascial flaps, or all of the above are used. The authors present 2 cases of postsurgical symptomatic giant pseudomeningoceles that were repaired using a fast-resorbing polymer mesh-supported reconstruction technique, which is described here for the first time.
Bergeron, Eric; Roux, Alain; Demers, Jacques; Vanier, Laurent E; Moore, Lynne
2010-11-01
We present a rare case of a rectothecal fistula arising from an anterior sacral meningocele in a patient with Currarino syndrome. The patient was a 40-year-old woman presenting with cauda equina syndrome and ascending meningitis. The meningocele was removed using an anterior abdominal approach. A sigmoid resection was performed with rectal on-table antegrade lavage followed by closure of the rectal fistula, closure of the rectal stump, and proximal colostomy. Closure of the sacral deficit was carried out by suturing a strip of well-vascularized omentum and fibrin glue. We discuss the characteristics, management, and evolution of this unusual case. Prompt surgical management using an anterior approach, resection of the sac, closure of the sacral deficit, and fecal diversion resulted in a satisfactory outcome.
A method to screen and evaluate tissue adhesives for joint repair applications
2012-01-01
Background Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications. Method Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates) of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3). Serial measurements (n = 5) in different operation modes (OM) were performed to analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage tissue either in isolation (OM-2) or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives. Results Viability analysis of test tissue cylinders revealed vital cells (>80%) in cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4-fold). The screening of the different collagen formulations revealed a substance with significant higher adhesive strength on cartilage (14.8 kPa) and bone tissue (11.8 kPa) compared to fibrin and also considerable adhesive properties when filling defects with cartilage tissue (23.2 kPa). Conclusion The method confirmed adhesive properties of fibrin and demonstrated the dependence of adhesive properties and applied settings. Furthermore the method was suitable to screen for potential adhesives and to identify a promising candidate for cartilage and bone applications. The method can offer simple, replicable and efficient evaluation of adhesive properties in ex vivo specimens and may be a useful supplement to existing methods in clinical relevant settings. PMID:22984926
[Emergency Surgery and Treatments for Pneumothorax].
Kurihara, Masatoshi
2015-07-01
The primary care in terms of emergency for pneumothorax is chest drainage in almost cases. The following cases of pneumothorax and the complications need something of surgery and treatments. Pneumothorax with subcutaneous emphysema often needs small skin incisions around the drainage tube. Tension pneumothorax often needs urgent chest drainage. Pneumothorax with intractable air leakage often needs interventional treatments like endobroncheal occlusion (EBO) or thoracographic fibrin glue sealing method (TGF) as well as urgent thoracoscopic surgery. Pneumothorax with acute empyema also often needs urgent thoracoscopic surgery within 2 weeks if chest drainage or drug therapy are unsuccessful. It will probably become chronic empyema of thorax after then. Pneumothorax with bleeding needs urgent thoracoscopic surgery in case of continuous bleeding over 200 ml/2 hours. In any cases of emergency for pneumothorax, respiratory physicians should collaborate with respiratory surgeons at the 1st stage because it is important to timely judge conversion of surgical treatments from medical treatments.
Surgical Treatment of Anorectal Crohn Disease
Lewis, Robert T.; Bleier, Joshua I. S.
2013-01-01
Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario. PMID:24436656
AMIC Cartilage Repair in a Professional Soccer Player
Bark, S.; Riepenhof, H.; Gille, J.
2012-01-01
We report a case of a professional soccer player suffering from a traumatic cartilage lesion grade IV according to the Outerbridge classification at the femoral condyle treated with an enhanced microfracture technique (AMIC). Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen scaffold and fibrin glue. Because of the cartilage lesion (3 cm2), an AMIC procedure was performed followed by a rehabilitation program according to the protocols in the literature, (Steadman et al.; 2003). After 8 months of rehabilitation, the player returned to team training and after 10 months to competition. Altogether he returned to the same skill level for almost one year after the index operation. He is very satisfied with the clinical results after AMIC, which corresponds with the Lysholm score of 90 points at 12 months. PMID:23259120
[Research progress on the management of no packing after septoplasty].
Lu, Sheng; Zhang, Longcheng; Li, Jieen
2016-01-01
Packing the nose after septoplasty is common practice. The use of postoperative packing has been proposed to reduce the dead space between the subperichondrial flaps and minimize postoperative complications such as hemorrhage, septal hematoma, and formation of synechiae. Additionally, postoperative packing is thought to stabilize the remaining cartilaginous septum and minimize persistence or recurrence of septal deviation. Despite these theoretic advantages, evidence to support the use of postoperative packing is lacking. Additionally, nasal packing is not an innocuous procedure. The use of nasal packing actually cause these complications such as postop- erative pain, mucosal injury, bleeding, worsening of breathing due to sleep disorders, and postoperative infections. Routine use of anterior nasal packing after septoplasty should be challenged for not presenting proven benefit. As alternatives to traditional packing, septal suturing, septal stapler and fibrin glue have been used recently. The purpose of this article is to summarize the progress of traditional packing to no packing after septoplasty.
Andrião-Escarso, S H; Sampaio, S V; Cunha, O A; Marangoni, S; Oliveira, B; Giglio, J R
1997-07-01
A detailed procedure for the isolation of a new clotting enzyme from the venom of Bothrops jararacussu (common name jararacuçu) is described. The estimated mol. wt of the native protein was 30,100 but 37,500 after reduction by dithiothreitol. Two major close bands corresponding to pI 5.18 and 5.20 were detected by electrofocusing but, after methanolysis, a single band focused at pI 8.20. The mol. wt of the protein moiety of this glycoprotein was 28,500, showing V-V-G-A-D-N-C-N-F-N... as N-terminal sequence. The content of neutral sugar was 4.8% and that of total sugars 5.3%. This clotting factor degraded only the A alpha-chain of the fibrinogen molecule. The stability of the clot, when produced in the presence of aprotinin opens new uses for snake clotting enzymes in the production of fibrin glue.
Casani, Augusto; Nuti, Daniele; Franceschini, Stefano Sellari; Gaudini, Elisa; Dallan, Iacopo
2005-12-01
To determine the effects of transtympanic injections, with a mixture composed of gentamicin and fibrin tissue adhesive (FTA), on vestibular function of patients with intractable unilateral Menière's disease. This was an open, prospective study. The study was performed at 2 tertiary referral centers. Twenty-six patients affected by "definite" unilateral Menière's disease, unresponsive to medical therapy for at least 6 months, were enrolled. A buffered gentamicin solution mixed with FTA was injected in the middle ear until the development of bedside vestibular hypofunction signs and/or caloric weakness in the treated ear. Vestibular function was evaluated by 3 bedside vestibular tests (observation of spontaneous nystagmus, head shaking test, and head thrust test) and by a caloric test. Tests were performed on days 10 and 30 after completion of treatment. Tests were also performed 3, 6, and 12 months from completion of the gentamicin-FTA protocol. The effects of treatment were also assessed in terms of hearing levels, control of vertigo, and disability status. In 22 of the 26 patients, only 1 gentamicin-FTA injection was necessary to obtain 1 or more signs indicating a reduction of the vestibular function in the treated ear. Four patients needed another treatment because of the persistence of their incapacitating symptoms during the follow-up. Four patients needed more than 1 injection to obtain a vestibular hypofunction. None of the patients who received 1 or 2 injections presented hearing loss in direct temporal relationship to the treatment. A mixture of gentamicin and fibrin glue makes it possible to considerably reduce the number of administrations in patients with intractable unilateral Menière's disease. Spontaneous nystagmus, post head shaking nystagmus, and a head thrust sign are the clinical signs that indicate onset or progression of unilateral vestibular hypofunction. These signs were obtained with only 1 injection in 81% of patients.
Schaakxs, Dominique; Kalbermatten, Daniel F; Pralong, Etienne; Raffoul, Wassim; Wiberg, Mikael; Kingham, Paul J
2017-03-01
Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Sun, Ping; Cheng, Xiang; Deng, Shichang; Hu, Qinggang; Sun, Yi; Zheng, Qichang
2017-02-07
Chronic pain following mesh-based inguinal hernia repair is frequently reported, and has a significant impact on quality of life. Whether mesh fixation with glue can reduce chronic pain without increasing the recurrence rate is still controversial. To determine whether tissue adhesives can reduce postoperative complications, especially chronic pain, with no increase in recurrence rate, compared with sutures for mesh fixation in Lichtenstein hernia repair. We searched the following electronic databases with no language restrictions: the Cochrane Central Register of Controlled Trials (CENTRAL; issue 4, 2016) in the Cochrane Library (searched 11 May 2016), MEDLINE Ovid (1986 to 11 May 2016), Embase Ovid (1986 to 11 May 2016), Science Citation Index (Web of Science) (1986 to 11 May 2016), CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), VIP (a full-text database in China), Wanfang databases. We also checked reference lists of identified papers (included studies and relevant reviews). We included all randomised and quasi-randomised controlled trials comparing glue versus sutures for mesh fixation in Lichtenstein hernia repair. Cluster-RCTs were also eligible. Two review authors extracted data and assessed the risk of bias independently. Dichotomous outcomes were expressed as odds ratio (OR) with 95% confidence intervals (CI). Continuous outcomes were expressed as mean differences (MD) with 95% CIs. Twelve trials with a total of 1932 participants were included in this review. The overall postoperative chronic pain in the glue group was reduced by 37% (OR 0.63, 95% CI 0.44 to 0.91; 10 studies, 1418 participants, low-quality evidence) compared with the suture group. However, the results changed when we conducted subgroup analysis with regard to the type of mesh. Subgroup analysis of included studies using lightweight mesh showed the reduction of chronic pain was less profound and insignificant (OR 0.77, 95% CI 0.50 to 1.17). Subgroup analysis of included studies using heavyweight mesh resulted in a significant benefit from the fixation with glue (OR 0.38, 95% CI 0.17 to 0.82).Hernia recurrence was similar between the two groups (OR 1.44, 95% CI 0.63 to 3.28; 12 studies, 1932 participants, low-quality evidence). Fixation with glue was superior to suture regarding duration of the operation (MD -3.13, 95% CI -4.48 to -1.78; 9 studies, 1790 participants, low-quality evidence); haematoma (OR 0.52, 95% CI 0.31 to 0.86; 10 studies, 1384 participants, moderate-quality evidence); and recovery time to daily activities (MD -1.26, 95% CI -1.89 to -0.63; 3 studies, 403 participants, low-quality evidence).We also investigated adverse events. There were no significant differences between the two groups. For superficial wound infection pooled analyses showed OR 1.23, 95% CI 0.37 to 4.11; 7 studies, 763 participants (low-quality evidence); for mesh/deep infection OR 0.67, 95% CI 0.16 to 2.83; 8 studies, 1393 participants (low-quality evidence). Furthermore, we investigated seroma (a postoperative swelling caused by fluid) (OR 0.83, 95% CI 0.51 to 1.33); and persisting numbness (OR 0.81, 95% CI 0.57 to 1.14).Finally, six trials involving 1009 participants reported postoperative length of stay, resulting in non-significant difference between the two groups (MD -0.12, 95% CI: -0.35 to 0.10)Due to the lack of data, it was impossible to draw any distinction between synthetic glue and biological glue.Eight out of 12 trials showed high risk of bias in at least one of the investigated domains. Two studies were quasi-randomised controlled trials and the allocation sequence of one trial was not concealed. Nearly half of the included trials either did not provide adequate information or had high risk of bias regarding blinding processes. The risk of bias for incomplete outcome data of all the included studies varied from low to high risk of bias. Two trials did not report on some important outcomes. One study was funded by the manufacturer producing the fibrin sealant. Therefore, according to the 'Summary of findings' tables, the quality of the evidence (GRADE) for the outcomes is moderate to low. Based on the short-term results, glue may reduce postoperative chronic pain and not simultaneously increase the recurrence rate, compared with sutures for mesh fixation in Lichtenstein hernia repair. Glue may therefore be a sensible alternative to suture for mesh fixation in Lichtenstein repair. Larger trials with longer follow-up and high quality are warranted. The difference between synthetic glue and biological glue should also be assessed in the future.
Zhu, Shu; Travers, Richard J.; Morrissey, James H.
2015-01-01
Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) –bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 μg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ∼0.1 to 2 molecules per μm2. Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per µm2 and sensitive to O1A6 at 0 to 0.2 molecules per µm2. However, neither antibody reduced fibrin generation at ∼2 molecules per µm2 when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per µm2) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall. PMID:26136249
Thermal gelation and tissue adhesion of biomimetic hydrogels
Burke, Sean A; Ritter-Jones, Marsha; Lee, Bruce P; Messersmith, Phillip B
2008-01-01
Marine and freshwater mussels are notorious foulers of natural and manmade surfaces, secreting specialized protein adhesives for rapid and durable attachment to wet substrates. Given the strong and water-resistant nature of mussel adhesive proteins, significant potential exists for mimicking their adhesive characteristics in bioinspired synthetic polymer materials. An important component of these proteins is L-3,4-dihydroxylphenylalanine (DOPA), an amino acid believed to contribute to mussel glue solidification through oxidation and crosslinking reactions. Synthetic polymers containing DOPA residues have previously been shown to crosslink into hydrogels upon the introduction of oxidizing reagents. Here we introduce a strategy for stimuli responsive gel formation of mussel adhesive protein mimetic polymers. Lipid vesicles with a bilayer melting transition of 37 °C were designed from a mixture of dipalmitoyl and dimyristoyl phosphatidylcholines and exploited for the release of a sequestered oxidizing reagent upon heating from ambient to physiologic temperature. Colorimetric studies indicated that sodium-periodate-loaded liposomes released their cargo at the phase transition temperature, and when used in conjunction with a DOPA-functionalized poly(ethylene glycol) polymer gave rise to rapid solidification of a crosslinked polymer hydrogel. The tissue adhesive properties of this biomimetic system were determined by in situ thermal gelation of liposome/polymer hydrogel between two porcine dermal tissue surfaces. Bond strength measurements showed that the bond formed by the adhesive hydrogel (mean = 35.1 kPa, SD = 12.5 kPa, n = 11) was several times stronger than a fibrin glue control tested under the same conditions. The results suggest a possible use of this biomimetic strategy for repair of soft tissues. PMID:18458476
Pan, Hung-Chuan; Yang, Dar-Yu; Ho, Shu-Peng; Sheu, Meei-Ling; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou
2009-08-23
Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.
Hemostatic Modifications of the Bentall Procedure
Della Corte, Alessandro; Baldascino, Francesco; La Marca, Francesca; Scardone, Michelangelo; Nappi, Gianantonio; Cefarelli, Mariano; De Santo, Luca S.; Pepino, Paolo; Cotrufo, Maurizio; De Feo, Marisa
2012-01-01
Bleeding is an important predictor of morbidity and mortality rates after the Bentall operation. This study reports our recent experience with composite aortic root replacement via a slightly modified button-Bentall operation. Fifty-six consecutive patients underwent a Bentall operation on an elective basis from January 2008 through December 2009. In all cases, we used 2 modifications: we imbricated the pledgeted 2-0 polyester interrupted U stitches of the proximal suture line, and at that same suture line we sealed with fibrin glue the possible sources of oozing. The series featured high proportions of associated procedures (25%) and reoperations (23%). The mean cardiopulmonary bypass and aortic cross-clamp times were 166 ± 50 and 113 ± 27 min, respectively. No case of operative or hospital (30-day) death was observed. Postoperative drainage amounted to 705 mL (median) on the first postoperative day and 377 mL (mean) on the second. Surgical re-exploration for bleeding was needed in only 1 patient (1.8%). Postoperative acute kidney injury was observed in 5 patients, neurologic complications in 3, and respiratory insufficiency requiring prolonged mechanical ventilation in another 3. Both respiratory and renal complications were significantly associated with greater consumption of blood products (P=0.03 and P=0.001, respectively). We conclude that the combined use of imbricated proximal suture-line stitches and subsequent fibrin-sealant spraying were associated with no deaths and with low rates of bleeding and other adverse postoperative sequelae in our 2-year experience with the Bentall operation in an elective series of patients characterized by a difficult mixture of prognoses. PMID:22740732
Repairing the vibratory vocal fold.
Long, Jennifer L
2018-01-01
A vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration. Translational research. Rabbit adipose-derived mesenchymal stem cells (ASC) were embedded within a three-dimensional fibrin gel, forming the cell-based outer vocal fold replacement (COVR). Sixteen rabbits underwent unilateral resection of vocal fold epithelium and lamina propria, as well as reconstruction with one of three treatments: fibrin glue alone with healing by secondary intention, replantation of autologous resected vocal fold cover, or COVR implantation. After 4 weeks, larynges were examined histologically and with phonation. Fifteen rabbits survived. All tissues incorporated well after implantation. After 1 month, both graft types improved histology and vibration relative to injured controls. Extracellular matrix (ECM) of the replanted mucosa was disrupted, and ECM of the COVR implants remained immature. Immune reaction was evident when male cells were implanted into female rabbits. Best histologic and short-term vibratory outcomes were achieved with COVR implants containing male cells implanted into male rabbits. Vocal fold cover replacement with a stem cell-based tissue-engineered construct is feasible and beneficial in acute rabbit implantation. Wound-modifying behavior of the COVR implant is judged to be an important factor in preventing fibrosis. NA. Laryngoscope, 128:153-159, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
Mastoid cortex plasty using bone pate.
Yanagihara, Naoaki; Hinohira, Yasuyuki; Sato, Hidemitu
2002-07-01
To describe the surgical technique of mastoid cortex plasty using bone pate and its clinical significance. Retrospective. Tertiary medical center. Bone pate collected while drilling the mastoid cortex was mixed with fibrin glue to make a pate plate. The mastoid cortex defect was closed with a pate plate cut to the desired shape and size. Mastoid cortex plasty was included in the first-stage operation in 49 patients who underwent staged tympanoplasty. The second-stage operation was an inspection to see whether the mastoid cortex was reconstructed and the ingrowth of fibrous soft tissue was prevented. In 35 patients, the mastoid cortex was reconstructed completely, and soft tissue ingrowth into the mastoid cavity was blocked completely. In the remaining 14 patients, a defect of varying size occurred at the site of drainage-tube insertion. This defect was small enough to prevent soft tissue ingrowth into the mastoid cavity. Mastoid cortex plasty is a simple and rapid procedure for preventing postoperative deformity of the mastoid process and is valuable for restoring mastoid cavity function.
Carey, Joseph N; Sheckter, Clifford C; Watt, Andrew J; Lee, Gordon K
2013-08-01
Despite advances in nutritional supplementation, sepsis management, percutaneous drainage and surgical technique, enterocutaneous fistulae remain a considerable source of morbidity and mortality. Use of adjunctive modalities including negative pressure wound therapy and fibrin glue have been shown to improve the rapidity of fistula closure; however, the overall rate of closure remains poor. The challenge of managing chronic, high-output proximal enterocutaneous fistulae can be successfully achieved with appropriate medical management and intra-abdominal placement of pedicled rectus abdominis muscle flaps. We report two cases of recalcitrant high output enterocutaneous fistulae that were treated successfully with pedicled intra-abdominal rectus muscle flaps. Indications for pedicled intra-abdominal rectus muscle flaps include persistent patency despite a reasonable trial of non-operative intervention, failure of traditional operative interventions (serosal patch, Graham patch), and persistent electrolyte and nutritional abnormalities in the setting of a high-output fistula. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Evaluation of hydrogels for soft tissue adhesives in vitro and in vivo analyses
NASA Astrophysics Data System (ADS)
Yuan, Liu; Fan, Wenshuai; Han, Linyingjun; Guo, Changan; Yan, Zuoqin; Zhu, Meifang; Mo, Xiumei
2018-03-01
In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson's trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.
2007-01-01
Stable films containing CdS quantum dots of mean size 3.4 nm embedded in a solid host matrix are prepared using a room temperature chemical route of synthesis. CdS/synthetic glue nanocomposites are characterized using high resolution transmission electron microscopy, infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Significant blue shift from the bulk absorption edge is observed in optical absorption as well as photoacoustic spectra indicating strong quantum confinement. The exciton transitions are better resolved in photoacoustic spectroscopy compared to optical absorption spectroscopy. We assign the first four bands observed in photoacoustic spectroscopy to 1se–1sh, 1pe–1ph, 1de–1dhand 2pe–2phtransitions using a non interacting particle model. Nonlinear absorption studies are done using z-scan technique with nanosecond pulses in the off resonant regime. The origin of optical limiting is predominantly two photon absorption mechanism.
Scattering of glue by glue on the light-cone worldsheet. II. Helicity conserving amplitudes
NASA Astrophysics Data System (ADS)
Chakrabarti, D.; Qiu, J.; Thorn, C. B.
2006-08-01
This is the second of a pair of articles on scattering of glue by glue, in which we give the light-cone gauge calculation of the one-loop on-shell helicity conserving scattering amplitudes for gluon-gluon scattering (neglecting quark loops). The 1/p+ factors in the gluon propagator are regulated by replacing p+ integrals with discretized sums omitting the p+=0 terms in each sum. We also employ a novel ultraviolet regulator that is convenient for the light-cone worldsheet description of planar Feynman diagrams. The helicity conserving scattering amplitudes are divergent in the infrared. The infrared divergences in the elastic one-loop amplitude are shown to cancel, in their contribution to cross sections, against ones in the cross section for unseen bremsstrahlung gluons. We include here the explicit calculation of the latter, because it assumes an unfamiliar form due to the peculiar way discretization of p+ regulates infrared divergences. In resolving the infrared divergences we employ a covariant definition of jets, which allows a transparent demonstration of the Lorentz invariance of our final results. Because we use an explicit cutoff of the ultraviolet divergences in exactly four spacetime dimensions, we must introduce explicit counterterms to achieve this final covariant result. These counterterms are polynomials in the external momenta of the precise order dictated by power counting. We discuss the modifications they entail for the light-cone worldsheet action that reproduces the bare planar diagrams of the gluonic sector of QCD. The simplest way to do this is to interpret the QCD string as moving in six spacetime dimensions.
Zhu, Shu; Travers, Richard J; Morrissey, James H; Diamond, Scott L
2015-09-17
Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) -bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 μg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ∼0.1 to 2 molecules per μm(2). Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per µm(2) and sensitive to O1A6 at 0 to 0.2 molecules per µm(2). However, neither antibody reduced fibrin generation at ∼2 molecules per µm(2) when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per µm(2)) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall. © 2015 by The American Society of Hematology.
Observation of laser-driven shock propagation by nanosecond time-resolved Raman spectroscopy
NASA Astrophysics Data System (ADS)
Yu, Guoyang; Zheng, Xianxu; Song, Yunfei; Zeng, Yangyang; Guo, Wencan; Zhao, Jun; Yang, Yanqiang
2015-01-01
An improved nanosecond time-resolved Raman spectroscopy is performed to observe laser-driven shock propagation in the anthracene/epoxy glue layer. The digital delay instead of optical delay line is introduced for sake of unlimited time range of detection, which enables the ability to observe both shock loading and shock unloading that always lasts several hundred nanoseconds. In this experiment, the peak pressure of shock wave, the pressure distribution, and the position of shock front in gauge layer were determined by fitting Raman spectra of anthracene using the Raman peak shift simulation. And, the velocity of shock wave was calculated by the time-dependent position of shock front.
Suzuki, Keitaro; Shinya, Masaru; Kitagawa, Michihiro
2006-04-01
We performed in vivo and in vitro adhesion experiments on the use of photocrosslinkable chitosan (PC) for healing of the myometrium and the amniotic membrane to test its usefulness in the perinatal field. To determine the adhesion conditions of PC in the healing of the myometrium and amniotic membrane, we applied two concentrations (30 and 50 mg/mL) of PC to the postpartum amniotic membrane, and radiated it with ultraviolet (UV) light for 10, 20, 30 or 60 s. Next, we created incisions of three sizes (pinhole, 5 mm and 10 mm), and performed PC adhesion followed by pressure application experiments. Subsequently, we laparotomized 12-day-pregnant rats under anesthesia, created a 5-mm incision, applied PC and closed the abdomen. We removed the uterus at 20 days of pregnancy, and histologically examined the site of PC application. The optimal adhesion conditions of PC were 50 mg/mL, and the optimal time of UV irradiation was 30 s or longer. In pressure application experiments, the bonding strength of PC was so high that even 10-mm incisions withstood a mean pressure of 92 mmH2O. The bonding strength of PC was significantly higher than that of fibrin glue that was tested in parallel. Histological examination of the rat myometrium showed a mild foreign body reaction with no inflammatory findings, confirming the usefulness of PC. PC is a wound-healing drug, an improvement on the naturally occurring polysaccharide chitosan, and is safer and has a higher bonding strength than biological adhesives including fibrin, making it promising for fetal surgical and perinatal applications.
Epstein, Nancy E
2015-01-01
Typically, fibrin sealants (FSs) and fibrin glues (FGs) are used to strengthen dural repairs during spinal surgery. In 2014, Epstein demonstrated that one FS/FG, Tisseel (Baxter International Inc., Westlake Village, CA, USA) equalized the average times to drain removal and length of stay (LOS) for patients with versus without excess bleeding (e.g. who did not receive Tisseel) undergoing multilevel laminectomies with 1-2 level noninstrumented fusions (LamF).[6]. Here Tisseel was utilized to promote hemostasis for two populations; 39 patients undergoing average 4.4 level lumbar laminectomies with average 1.3 level noninstrumented fusions (LamF), and 48 patients undergoing average 4.0 level laminectomies alone (Lam). We compared the average operative time, estimated blood loss (EBL), postoperative drainage, LOS, and transfusion requirements for the LamF versus Lam groups. The average operative times, EBL, postoperative drainage, LOS, and transfusion requirements were all greater for LamF versus Lam patients; operative times (4.1 vs. 3.0 h), average EBL (192.3 vs. 147.9 cc), drainage (e.g. day 1; 199.6 vs. 167.4 cc; day 2; 172.9 vs. 63.9 cc), average LOS (4.6 vs. 2.5 days), and transfusion requirements (11 LamF patients; 18 Units [U] RBC versus 2 Lam patients; 3 U RBC). Utilizing Tisseel to facilitate hemostasis in LamF versus Lam still resulted in greater operative times, EBL, postoperative average drainage, LOS, and transfusion requirements for patients undergoing the noninstrumented fusions. Although Tisseel decreases back bleeding within the spinal canal, it does not reduce blood loss from LamF decorticated transverse processes.
Tisseel utilized as hemostatic in spine surgery impacts time to drain removal and length of stay.
Epstein, Nancy E
2014-01-01
Although fibrin sealants (FSs) and fibrin glues (FGs) are predominantly utilized to strengthen repairs of cerebrospinal fluid (CSF) fistulas (deliberate/traumatic) during spinal surgery, they are also increasingly utilized to achieve hemostasis. Here, we investigated whether adding Tisseel (Baxter International Inc., Westlake Village, CA, USA), utilized to address increased bleeding during multilevel lumbar laminectomies with non-instrumented fusions, would reduce or equalize the time to drain removal and length of stay (LOS) without contributing to infections or prolonging time to fusion. Prospectively, 39 patients underwent multilevel laminectomies and 1-2 level non-instrumented (in situ) fusions to address stenosis/olisthesis; 22 who demonstrated increased intraoperative bleeding received Tisseel, while 17 without such bleeding did not. The 22 receiving versus 17 not receiving Tisseel, with similar clinical parameters, underwent comparable average multilevel laminectomies (4.36 and 4.25) and 1-2 level fusions (1.4 vs. 1.29 levels). As anticipated, for those receiving Tisseel, the average intraoperative estimated blood loss (EBL), total postoperative blood loss, and total perioperative transfusion requirements [red blood cells (RBC), fresh frozen plasma (FFP), platelets] were higher. However, Tisseel had the added benefit of equalizing the time to postoperative drain removal [e.g. 3.41 days (with) vs. 3.38 days (without)] and LOS [e.g. 5.86 days (with) vs. 5.82 days (without)] without increasing the infection rates (e.g. one superficial infection per group) or average times to fusion (e.g. 5.9 vs. 5.5 months). Adding Tisseel for increased bleeding during multilevel laminectomies/in situ fusions contributed to hemostasis by equalizing the average times to drain removal/LOS compared to patients without increased bleeding and not requiring Tisseel.
Vidal-Pérez, Óscar; Flores-Siguenza, Luis; Valentini, Mauro; Astudillo-Pombo, Emiliano; Fernández-Cruz, Laureano; García-Valdecasas, Juan Carlos
2016-01-01
In recent years, several publications have shown that new adhesives and sealants, like Tissucol(®), applied in thyroid space reduce local complications after thyroidectomies. To demonstrate the effectiveness of fibrin glue Tissucol(®) in reducing the post-operative hospital stay of patients operated on for differentiated thyroid carcinoma in which total thyroidectomy with central and unilateral node neck dissection was performed (due to the debit drains decrease), with consequent cost savings. A prospective randomised study was conducted during the period between May 2009 and October 2013 on patients with differentiated thyroid carcinoma with cervical nodal metastases, and subjected to elective surgery. Two groups were formed: one in which Tissucol(®) was used (case group) and another where it was not used (control group). Patients were operated on by surgeons specifically dedicated to endocrine surgical pathology, using the same surgical technique in all cases. A total of 60 total thyroidectomies with lymph node dissection were performed, with 30 patients in the case group, and 30 patients in control group. No statistically significant differences were observed in most of the studied variables. However, the case group had a shorter hospital stay than the control group with a statistically significant difference (p<0.05). Implementation of Tissucol(®) has statistically and significantly reduced the hospital stay of patients undergoing total thyroidectomy with neck dissection, which represents a significant reduction in hospital costs. This decrease in hospital stay has no influence on the occurrence of major complications related to the intervention. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Sung, H W; Huang, D M; Chang, W H; Huang, R N; Hsu, J C
1999-09-15
Bioadhesives are used for tissue adhesion and hemostasis in surgery. A gelatin-resorcinol mixture crosslinked with formaldehyde (GRF glue) and/or glutaraldehyde (GRG) is used for this purpose. Although the bonding strength of the GRF glue to tissue is satisfactory, concerns about the cytotoxicity of formaldehyde are reported in the literature. It was suggested that the cytotoxicity problem of the GRF glue may be overcome by changing its crosslinking method. The study was therefore undertaken to assess the feasibility of using an epoxy compound (GRE glue), a water-soluble carbodiimide (GAC glue), or genipin (GG glue) to crosslink with a gelatin hydrogel as new bioadhesives. GRF glue and GRG glue were used as controls. The results of our cytotoxicity study suggested that the cellular compatibility of the GAC and GG glues was superior to the GRF, GRG, and GRE glues. The gelation time for the GG glue was relatively longer than the GRF and GRG glues, while no gelation time could be determined for the GAC glue. Additionally, it took approximately 17 h for the GRE glue to become adhesive. The GRF and GRG glues had the greatest bonding strengths to tissue among all test adhesives, while the bonding strengths of the GAC and GG glues were comparable. In contrast, there was almost no bonding strength to tissue for the GRE glue. However, the GRF and GRG glues were less flexible than the GAC and GG glues. Subsequent to the bonding strength measurement, each test adhesive was found to adhere firmly to the tissue surface and underwent cohesive failure during the bond breaking. In conclusion, the GRF and GRG glues may be used as tissue adhesives when their ability to bind tissue rapidly and tightly is required; the GAC and GG glues are preferable when the adhesive action must be accompanied with minimal cytotoxicity and stiffness; and the GRE glue is not suitable for bioadhesion in clinical applications. Copyright 1999 John Wiley & Sons, Inc.
Dextran and gelatin based photocrosslinkable tissue adhesive.
Wang, Tao; Nie, Jun; Yang, Dongzhi
2012-11-06
A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.
Guo, Jinshan; Kim, Gloria B.; Shan, Dingying; Kim, Jimin P.; Hu, Jianqing; Wang, Wei; Hamad, Fawzi G.; Qian, Guoying; Rizk, Elias B.; Yang, Jian
2016-01-01
For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge to developing such an adhesive was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management. PMID:27770631
Photoactivated methods for enabling cartilage-to-cartilage tissue fixation
NASA Astrophysics Data System (ADS)
Sitterle, Valerie B.; Roberts, David W.
2003-06-01
The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.
Traumatic laryngotracheal stenosis--an alternative surgical technique.
Syal, Rajan; Tyagi, Isha; Goyal, Amit
2006-02-01
Reconstruction of combined laryngotracheal stenosis requires complex techniques including resection and incorporation of grafts and stents that can be performed as single or multistaged procedure. A complicated case of traumatic laryngotracheal stenosis was managed by us, surgical technique is discussed. A 16-year-old male presented with Stage-3 laryngotracheal stenosis of grade-3 to 4 (>70% of the complete obstruction of tracheal lumen) of 5 cm segment of the larynx and trachea. Restoration of the critical functions of respiration and phonation was achieved in this patient by resection anastomosis of the trachea and with subglottic remodeling. Resection of 5 cm long segment of trachea and primary anastomosis in this case would have created tension at the site of anastomosis. So we did tracheal resection of 3 cm segment of trachea along with subglottic remodeling instead of removing the 5 cm segment of stenosed laryngotracheal region and doing thyrotracheal anastomosis. In complicated long segment, laryngotracheal stenosis, tracheal resection and subglottic remodeling with primary anastomosis can be an alternative approach. Fibrin glue can be used to support free bone/cartilage grafts in laryngotracheal reconstructions.
Injectible candidate sealants for fetal membrane repair: Bonding and toxicity in vitro
Bilic, Grozdana; Brubaker, Carrie; Messersmith, Phillip B.; Mallik, Ajit S.; Quinn, Thomas M.; Haller, Claudia; Done, Elisa; Gucciardo, Leonardo; Zeisberger, Steffen M.; Zimmermann, Roland; Deprest, Jan; Zisch, Andreas H.
2010-01-01
Objective This study was undertaken to test injectible surgical sealants that are biocompatible with fetal membranes, eventually for closure of iatrogenic membrane defects. Study Design Dermabond, Histoacryl, Tissucol fibrin glue, and three types of in situ forming poly(ethylene glycol)-based polymer hydrogels were tested for acute toxicity upon direct contact with fetal membranes for 24h. For determination of elution toxicity, extracts of sealants were incubated on amnion cell cultures for 72h. Bonding and toxicity was assessed through morphological and/or biochemical analysis. Results Extracts of all adhesives were non-toxic for cultured cells. However, only Tissucol and one type of poly(ethylene glycol)-based hydrogel, mussel-mimetic tissue adhesive, showed efficient, non-disruptive, non-toxic bonding to fetal membranes. Mussel-mimetic tissue adhesive applied over membrane defects created with a 3.5 mm trocar accomplished leak-proof closure that withstood membrane stretch in an in vitro model. Conclusion A synthetic hydrogel-type tissue adhesive emerged as potential sealing modality for iatrogenic membrane defects that merits further evaluation in vivo. PMID:20096254
Caged Molecular Glues as Photoactivatable Tags for Nuclear Translocation of Guests in Living Cells.
Arisaka, Akio; Mogaki, Rina; Okuro, Kou; Aida, Takuzo
2018-02-21
We developed dendritic caged molecular glues ( Caged Glue-R) as tags for nucleus-targeted drug delivery, whose multiple guanidinium ion (Gu + ) pendants are protected by an anionic photocleavable unit (butyrate-substituted nitroveratryloxycarbonyl; BA NVOC). Negatively charged Caged Glue-R hardly binds to anionic biomolecules because of their electrostatic repulsion. However, upon exposure of Caged Glue-R to UV light or near-infrared (NIR) light, the BA NVOC groups of Caged Glue-R are rapidly detached to yield an uncaged molecular glue ( Uncaged Glue-R) that carries multiple Gu + pendants. Because Gu + forms a salt bridge with PO 4 - , Uncaged Glue-R tightly adheres to anionic biomolecules such as DNA and phospholipids in cell membranes by a multivalent salt-bridge formation. When tagged with Caged Glue-R, guests can be taken up into living cells via endocytosis and hide in endosomes. However, when the Caged Glue-R tag is photochemically uncaged to form Uncaged Glue-R, the guests escape from the endosome and migrate into the cytoplasm followed by the cell nucleus. We demonstrated that quantum dots (QDs) tagged with Caged Glue-R can be delivered efficiently to cell nuclei eventually by irradiation with light.
Wang, Pengfei; Wang, Jian; Zhang, Wenbo; Li, Yousheng; Li, Jieshou
2009-03-01
Intra-abdominal sepsis and hemorrhagic shock have been found to impair the healing of intestinal anastomoses. The present study examined whether fibrin glue (FG) and recombinant human growth hormone (GH) can improve intestinal primary anastomotic healing in a pig model of traumatic shock associated with peritonitis. Further, the study was designed to investigate the probable mechanism of these agents. Female anesthetized pigs were divided into five groups. Group sham (n = 7), pigs without traumatic shock had small bowel resection anastomoses; group control (n = 14), pigs had bowel resection anastomoses 24 h after abdominal gunshot plus exsanguination/resuscitation; group FG (n = 14); group GH (n = 14); group FG/GH (n = 14), pigs received FG, recombinant GH, or both, respectively. Recombinant GH was given daily for 7 days. Blood samples were collected daily for measurement of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha levels. Investigations also included adhesion formation, anastomotic bursting pressure, tensile strength, hydroxyproline (HP) content, myeloperoxidase (MPO), tumor necrosis factor (NF)-kappaB activity, and histology analysis 10 days later. A second experiment (n = 20 subjects assigned to each of the five groups) was designed to study survival during the first 20 postoperative days. Traumatic shock associated with peritonitis led to significant decreases in intestinal anastomotic bursting pressures, tensile strengths, and tissue hydroxyproline content, along with severe adhesion formation, increases in MPO activity and NF-kappaB activity, and plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Both FG and recombinant GH treatment led to early significant increases in plasma levels of TNF-alpha and IL-6. At the same time, FG alone, unlike recombinant GH alone, led to significant increases in anastomotic bursting pressures, tensile strength, and tissue HP content, along with decreases in anastomotic MPO and NF-kappaB activity and later plasma levels of TNF-a and IL-6. The FG group also developed more marked neoangiogenesis and collagen deposition on histology analysis. However, FG and recombinant GH synergistically effected improved anastomotic healing, abolishing the infaust effects promoted by recombinant GH. Adhesion formation after intestinal anastomosis could not be lowered by FG alone or by the combination of FG and recombinant GH. Both FG alone and FG/GH, in contrast to GH alone and control treatment, significantly prolonged the survival time of experimental animals. We found that FG, but not recombinant GH, could lower the risk of anastomotic leakage, improve intestinal anastomotic healing, and prolong survival in a pig model of traumatic shock associated with peritonitis. Both FG and recombinant GH synergistically effected improved intestinal anastomotic healing. It was suggested that GH could be used locally to promote intestinal anastomotic healing in intra-abdominal peritonitis.
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... Animal glue. Animal glue may be safely used as a component of articles intended for use in producing... the provisions of this section. (a) Animal glue consists of the proteinaceous extractives obtained...
Serum aluminium levels in glue-sniffer adolescent and in glue containers.
Akay, Cemal; Kalman, Süleyman; Dündaröz, Ruşen; Sayal, Ahmet; Aydin, Ahmet; Ozkan, Yalçin; Gül, Hüsamettin
2008-05-01
Glue sniffing is a serious medical problem among teenagers. Various chemical substances such as toluene and benzene containing glues have been reported to be toxic. It has been demonstrated that some toxic metals such as lead are elevated in the blood of solvent-addicted patients. Whereas aluminium is an element that has toxic effects on neurological, hematopoetic system and bone metabolism. We want to determine the serum levels of aluminium in glue-sniffer adolescents in comparison with healthy subjects. In addition, we compared aluminium levels of different commercial glue preparations (i.e. metal and plastic containers), to determine which type of container is better for less aluminium toxicity. We measured serum levels of aluminium in 37 glue-sniffer and 37 healthy subjects using atomic absorption spectrophotometry. The average duration of glue-sniffer was 3.8 +/- 0.8 years. We also measured aluminium levels of 10 commercial glue preparations that seven of them with metal and three with plastic containers. We found that serum levels of aluminium were 63.29 +/- 13.20 ng/ml and 36.7 +/- 8.60 ng/ml in glue-sniffer and in control subjects, respectively (P < 0.001). The average aluminium level in the glues was 8.6 +/- 3.24 ng/g in the preparations with metal containers, whereas 3.03 +/- 0.76 ng/g with plastic containers (P < 0.001). Therefore, to decrease the incidence of aluminium toxicity in glue-sniffers, it may be a good step to market of glue preparations in plastic instead of metal containers.
Zamolodchikov, Daria
2012-01-01
Alzheimer disease is characterized by the presence of increased levels of the β-amyloid peptide (Aβ) in the brain parenchyma and cerebral blood vessels. This accumulated Aβ can bind to fibrin(ogen) and render fibrin clots more resistant to degradation. Here, we demonstrate that Aβ42 specifically binds to fibrin and induces a tighter fibrin network characterized by thinner fibers and increased resistance to lysis. However, Aβ42-induced structural changes cannot be the sole mechanism of delayed lysis because Aβ overlaid on normal preformed clots also binds to fibrin and delays lysis without altering clot structure. In this regard, we show that Aβ interferes with the binding of plasminogen to fibrin, which could impair plasmin generation and fibrin degradation. Indeed, plasmin generation by tissue plasminogen activator (tPA), but not streptokinase, is slowed in fibrin clots containing Aβ42, and clot lysis by plasmin, but not trypsin, is delayed. Notably, plasmin and tPA activities, as well as tPA-dependent generation of plasmin in solution, are not decreased in the presence of Aβ42. Our results indicate the existence of 2 mechanisms of Aβ42 involvement in delayed fibrinolysis: (1) through the induction of a tighter fibrin network composed of thinner fibers, and (2) through inhibition of plasmin(ogen)–fibrin binding. PMID:22238323
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of the...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of the...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of the...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of the...
Comparison of fibrin clots derived from peripheral blood and bone marrow.
Shoji, Takeshi; Nakasa, Tomoyuki; Yoshizuka, Masaaki; Yamasaki, Takuma; Yasunaga, Yuji; Adachi, Nobuo; Ochi, Mitsuo
2017-03-01
Autologous fibrin clots derived from peripheral blood (pb-fibrin clot) and bone marrow (bm-fibrin clot) are thought to be effective for tissue regeneration. However, there is no report detailing the amount of growth factors in pb-/bm-fibrin clot. In this study we evaluated the amount of growth factors in human pb-/bm-fibrin clot, and prove the validity of fibrin clot for clinical use. Human pb-/bm-fibrin clots were obtained during surgery. In the first experiment, enzyme-linked immunosorbent assay (ELISA) was performed for detecting the amount of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor basic (bFGF), hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-β), platelet derived-growth factors-AB (PDGF-AB), and stromal cell-derived factor-1 (SDF-1). In the second experiment, the efficacy of fibrin clot on the osteogenic differentiation and fibroblast proliferation was evaluated. Pb-/bm-fibrin clots were incubated in human osteoblast derived from mesenchymal stromal cells (MSCs) or human skin fibroblast. Alizarin red staining and real-time PCR (COL1A1, RUNX2) were performed for the detection of osteogenic potential. Cell-growth assay (WST-8) and real-time PCR (COL1A1) were also performed for the detection of the potential of fibroblast proliferation. ELISA analysis revealed that the amount of VEGF, HGF, bFGF, IGF-1, and SDF-1 of bm-fibrin clot group is higher than that of pb-fibrin clot group with statistical differences. Besides, we confirmed that bm-fibrin clot has much potential for the osteogenic differentiation and fibroblast proliferation. The positive outcomes confirm the efficacy of pb-/bm-fibrin clot, and bm-fibrin clot was proved to have much potential for tissue regeneration compared with pb-fibrin clot. The current study showed the potential of a strategy for regenerative medicine using bm-fibrin clot.
Fibronectin alters the rate of formation and structure of the fibrin matrix.
Ramanathan, Anand; Karuri, Nancy
2014-01-10
Plasma fibronectin is a vital component of the fibrin clot; however its role on clot structure is not clearly understood. The goal of this study was to examine the influence of fibronectin on the kinetics of formation, structural characteristics and composition of reconstituted fibrin clots or fibrin matrices. Fibrin matrices were formed by adding thrombin to 1, 2 or 4 mg/ml fibrinogen supplemented with 0-0.4 mg/ml fibronectin. The rate of fibrin matrix formation was then monitored by measuring light absorbance properties at different time points. Confocal microscopy of fluorescein conjugated fibrinogen was used to visualize the structural characteristics of fibrin matrices. The amount of fibronectin in fibrin matrices was determined through electrophoresis and immunoblotting of solubilized matrices. Fibronectin concentration positively correlated with the initial rate of fibrin matrix formation and with steady state light absorbance values of fibrin matrices. An increase in fibronectin concentration resulted in thinner and denser fibers in the fibrin matrices. Electrophoresis and immunoblotting showed that fibronectin was covalently and non-covalently bound to fibrin matrices and in the form of high molecular weight multimers. The formation of fibronectin multimers was attributed to cross-linking of fibronectin by trace amounts Factor XIIIa. These findings are novel because they link results from light absorbance studies to microcopy analyses and demonstrate an influence of fibronectin on fibrin matrix structural characteristics. This data is important in developing therapies that destabilize fibrin clots. Copyright © 2014. Published by Elsevier Inc.
Compounds from silicones alter enzyme activity in curing barnacle glue and model enzymes.
Rittschof, Daniel; Orihuela, Beatriz; Harder, Tilmann; Stafslien, Shane; Chisholm, Bret; Dickinson, Gary H
2011-02-17
Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties. Altered curing of natural glues has potential in fouling management.
Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes
Rittschof, Daniel; Orihuela, Beatriz; Harder, Tilmann; Stafslien, Shane; Chisholm, Bret; Dickinson, Gary H.
2011-01-01
Background Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. Methodology/Principal Findings GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Conclusions/Significance Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties. Altered curing of natural glues has potential in fouling management. PMID:21379573
Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.
Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung
2015-12-01
Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.
Bandura, Patrick; Rawnaq, Tamina; Holzknecht, Annette; Cetin, Emine; Reemts, Petra; Zoi, Panagiota; Schwärzler, Peter
2018-02-01
AVMs are rare tumorous vascular lesions derived from placental tissue that may present with massive post-partum hemorrhage (PPH) causing potentially life-threatening anemic shock. Current treatment options include the embolization of uterine arteries and emergency postpartum hysterectomy. We present a new form of minimally invasive, highly specific sonographically guided treatment in the form of the application of a human fibrin sealant leading to the instant cease of blood loss. A management protocol was established and a case series of 14 patients is presented. Diagnosis by endovaginal color Doppler sonography is followed by the sonographically guided application of biological glue (TISSEEL ® ), thus allowing for super-selective occlusion of the feeding vessels. The procedure was technically successful in all 14 patients, 3 of whom (21 %) had a repeated procedure after 4 - 7 days. The mean age (yrs.) of the patients was 31 (25 - 40), the gravity was median 2 (1 - 5) and the parity was median 1 (0 - 4), the lowest Hb value was on average 9.35 ± 2.25 (5.2 - 14.2) g/dl, the lowest Ht was on average 30.82 ± 6.02 (18 - 41 %). Spectral Doppler analysis revealed an average of 80.71 ± 11.2 (66 - 115) cm/sec for the maximal detectable PSV. In the period of 4 - 55 months after treatment, 7 patients (50 %) had 8 successful pregnancies and 2 miscarriages. In PPH there is vital interest in timely diagnosis of the underlying cause, thus allowing fertility-sparing, minimally invasive and super-selective emergency treatment. In AVMs causing PPH, a positive impact on perinatal morbidity and mortality may be achieved by sonographically guided application of this biological glue. © Georg Thieme Verlag KG Stuttgart · New York.
Use of radiation in biomaterials science
NASA Astrophysics Data System (ADS)
Benson, Roberto S.
2002-05-01
Radiation is widely used in the biomaterials science for surface modification, sterilization and to improve bulk properties. Radiation is also used to design of biochips, and in situ photopolymerizable of bioadhesives. The energy sources most commonly used in the irradiation of biomaterials are high-energy electrons, gamma radiation, ultraviolet (UV) and visible light. Surface modification involves placement of selective chemical moieties on the surface of a material by chemical reactions to improve biointeraction for cell adhesion and proliferation, hemocompatibility and water absorption. The exposure of a polymer to radiation, especially ionizing radiation, can lead to chain scission or crosslinking with changes in bulk and surface properties. Sterilization by irradiation is designed to inactivate most pathogens from the surface of biomedical devices. An overview of the use of gamma and UV radiation to improve surface tissue compatibility, bulk properties and surface properties for wear resistance, formation of hydrogels and curing dental sealants and bone adhesives is presented. Gamma and vacuum ultraviolet (VUV) irradiated ultrahigh molecular weight polyethylene (UHMWPE) exhibit improvement in surface modulus and hardness. The surface modulus and hardness of UHMWPE showed a dependence on type of radiation, dosage and processing. VUV surface modified e-PTFE vascular grafts exhibit increases in hydrophilicity and improvement towards adhesion of fibrin glue.
Repair of Inaccessible Ventral Dural Defect in Thoracic Spine: Double Layered Duraplasty
Lee, Dong-Hyun; Park, Jeong-Ill; Park, Ki-Su; Cho, Dae-Chul; Sung, Joo-Kyung
2016-01-01
We propose a double layered (intradural and epidural patch) duraplasty that utilizes Lyoplant and Duraseal. We examined a 47-year-old woman after decompression for thoracic ossification of posterior longitudinal ligament was performed in another hospital. On postoperative day 7, she complained of weakness in both legs. Postoperative magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) collection with cord compression. In the operative field, we found 2 large dural defects on the ventral dura mater. We performed a conventional fat graft with fibrin glue. However, the patient exhibited neurologic deterioration, and a postoperative MRI again showed CSF collection. We performed dorsal midline durotomy and inserted a intradural and epidural Lyoplant patch. She immediately experienced diminishing back pain postoperatively. Her visual analog scale and motor power improved markedly. Postoperative MRIs performed at 2 and 16 months showed no spinal cord compression or CSF leakage to the epidural space. We describe a new technique for double layered duraplasty. Although we do not recommend this technique for all dural repairs, double-layered duraplasty may be useful for repairing large inaccessible dural tears in cases of persistent CSF leakage refractory to conventional management. PMID:27437022
Laparoscopic left hepatectomy in swine: a safe and feasible technique.
Zhang, Hua; Liu, Tao; Wang, Yue; Liu, Hai-Feng; Zhang, Jian-Tao; Wu, Yan-Shuang; Lei, Lei; Wang, Hong-Bin
2014-01-01
A purely laparoscopic four-port approach was created for left hepatectomy in pigs. A polyethylene loop was placed on the left two hepatic lobes for traction and lift. Next, penetrating ligation of the lobes using of a double row of silk sutures was performed to control bleeding. A direct hepatic transection was completed using a monopolar hook electrode without meticulous dissection of the left hepatic vein. The raw surface of the liver was coagulated and sealed with fibrin glue. Lobes were retrieved through an enlarged portal. Laparoscopic hepatic lobectomy was completed in all pigs without the use of specialized instruments and with a mean operative time of 179 ± 9 min. No significant perioperative complications were observed. The average weight of each resected lobe was 180 ± 51 g. Complete blood count as well as serum organics and enzyme levels normalized after about 2 weeks. During necropsy, adhesion of the hepatic raw surface to the gastric wall and omentum were observed. No other abnormalities were identified. This minimally invasive left hepatectomy technique in swine could serve as a useful model for investigating liver diseases and regeneration, and offer preclinical information to improve hepatobiliary surgical procedures.
Crypto-glandular fistulous paraproctites--is the surgical prophylaxis of reccurences imperative?
Radionov, M; Ziya, D D; Sechanov, I
2013-01-01
It is done an analysis of 191 patients operated on for crypto-glandular chronic fistulous paraproctitis. The age of the patients vary 21 to 76 years and the male:female proportion is 2,25 to 1. In 164 patients it was first operation for fistula-in-ano and in 27 cases it was a consecutive one for reccurence. There was intervened a concomitant other disease of the anal channel which pathogenetically predispose the development of fistula in 54 (28%) cases. The patients were discharged 1-3 days after surgery. Ambulant control and ligature procedures up to the 30th day were done. A follow up was done of 118 patients (68%) for period of 3 to 12 months. In all the followed up patients was registered full continence and good tonus of the anal sphincters. Recurrences were registered in 8 cases with fibrin glue occlusion of the fistula. There are no registered cases of recurrences by the followed up patients after fistulotomy and excision-ligature methods. The authors review in the discussion the pathogenetical predisposition for paraproctitis in consequence of other diseases of the anal channel and the necessity of surgical prophylaxis of recurrences.
Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace
2018-01-01
Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.
Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace
2018-01-01
Background: Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Methods: Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso–Beattie–Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Results: Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Conclusions: Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery. PMID:29497572
Use of duraseal in repair of cerebrospinal fluid leaks.
Chin, Christopher J; Kus, Lukas; Rotenberg, Brian W
2010-10-01
The purpose of our article is to review the use of the DuraSeal Sealant System (Confluent Surgical Inc., Waltham, MA) in the repair of complex cerebrospinal fluid (CSF) leaks in endoscopic skull-base surgery. Retrospective chart review. London Health Sciences Centre. A database of endoscopic skull-base cases between 2007 and 2009 that involved CSF leakage repaired with DuraSeal was created. Demographic data and operative reports were collected and analyzed qualitatively. Recurrence of CSF leak after repair. Five cases were identified that met study criteria. In four of the five cases, the repair was successful. There were no complications related to DuraSeal use. Comparison to a subset of patients using Tisseel Fibrin Sealant (Baxter, Toronto, ON) for repair did not show a significant difference in failure rate (χ2 = 0.029, p = .858). There are a variety of techniques described to repair CSF rhinorrhea, with various studies demonstrating the advantages of using tissue glues in CSF leak repairs. We used DuraSeal in five patients to enhance graft strength and form a watertight seal. The system was effective in the majority of patients. Our study is the first to report on endoscopic endonasal repair of CSF leaks using DuraSeal.
Low cytotoxic tissue adhesive based on oxidized dextran and epsilon-poly-L-lysine.
Hyon, Suong-Hyu; Nakajima, Naoki; Sugai, Hajime; Matsumura, Kazuaki
2014-08-01
A novel adhesive hydrogel consisting of dextran and epsilon-poly(L-lysine) (dextran-PL) with multiple biomedical applications was developed. Periodate oxidation in aqueous media almost stoichiometrically introduces aldehyde groups in dextran molecules, and aldehyde dextran can react with the primary amino groups in epsilon-PL (ɛ-PL) at neutral pH to form a hydrogel. The gelation time of the hydrogel can be easily controlled by the extent of oxidation in dextran and of the acylation in ɛ-PL by anhydrides. The shear adhesion strength of dextran-PL was 10 times higher than that of fibrin glue, when wet collagen sheets were selected as test specimens. The cytotoxicity of aldehyde dextran and ɛ-PL were 1000 times lower than that of glutaraldehyde and poly(allylamine). The considerably low cytotoxicity of aldehyde dextran could be ascribed to its low reactivity with amine species when compared with glutaraldehyde. In contrast, a high reactivity of amino groups in ɛ-PL was observed when compared with glycine, L-lysine, and gelatin, which could be explained by their poor dissociation at neutral pH, thus leading to low cytotoxicity. © 2013 Wiley Periodicals, Inc.
A Giant Lumbar Pseudomeningocele in a Patient with Neurofibromatosis Type 1: A Case Report.
Dobran, Mauro; Iacoangeli, Maurizio; Ruscelli, Paolo; Della Costanza, Martina; Nasi, Davide; Scerrati, Massimo
2017-01-01
This is a rare case of giant lumbar pseudomeningocele with intra-abdominal extension in patient with neurofibromatosis type 1 (NF1). The patient's clinical course is retrospectively reviewed. A 34-year-old female affected by NF1 was referred to our institution for persistent low back pain and MRI diagnosis of pseudomeningocele located at L3 level with paravertebral extension. From the first surgical procedure by a posterior approach until the relapse of the pseudomeningocele documented by MRI, the patient underwent two subsequent posterior surgical procedures to repair the dural sac defect with fat graft and fibrin glue. One month after the third operation, the abdominal MRI showed a giant intra-abdominal pseudomeningocele causing compression of visceral structures. The patient was asymptomatic. The pseudomeningocele was treated with an anterior abdominal approach and the use of the acellular dermal matrix (ADM) sutured directly on the dural defect on the anterolateral wall of the spinal canal. After six months of follow-up the MRI showed no relapse of the pseudomeningocele. Our case highlights the possible use of ADM as an effective and safe alternative to the traditional fat graft to repair challenging and large dural defects.
Fibrin mechanical properties and their structural origins.
Litvinov, Rustem I; Weisel, John W
2017-07-01
Fibrin is a protein polymer that is essential for hemostasis and thrombosis, wound healing, and several other biological functions and pathological conditions that involve extracellular matrix. In addition to molecular and cellular interactions, fibrin mechanics has been recently shown to underlie clot behavior in the highly dynamic intra- and extravascular environments. Fibrin has both elastic and viscous properties. Perhaps the most remarkable rheological feature of the fibrin network is an extremely high elasticity and stability despite very low protein content. Another important mechanical property that is common to many filamentous protein polymers but not other polymers is stiffening occurring in response to shear, tension, or compression. New data has begun to provide a structural basis for the unique mechanical behavior of fibrin that originates from its complex multi-scale hierarchical structure. The mechanical behavior of the whole fibrin gel is governed largely by the properties of single fibers and their ensembles, including changes in fiber orientation, stretching, bending, and buckling. The properties of individual fibrin fibers are determined by the number and packing arrangements of double-stranded half-staggered protofibrils, which still remain poorly understood. It has also been proposed that forced unfolding of sub-molecular structures, including elongation of flexible and relatively unstructured portions of fibrin molecules, can contribute to fibrin deformations. In spite of a great increase in our knowledge of the structural mechanics of fibrin, much about the mechanisms of fibrin's biological functions remains unknown. Fibrin deformability is not only an essential part of the biomechanics of hemostasis and thrombosis, but also a rapidly developing field of bioengineering that uses fibrin as a versatile biomaterial with exceptional and tunable biochemical and mechanical properties. Copyright © 2016 Elsevier B.V. All rights reserved.
Elastic Behavior and Platelet Retraction in Low- and High-Density Fibrin Gels
Wufsus, Adam R.; Rana, Kuldeepsinh; Brown, Andrea; Dorgan, John R.; Liberatore, Matthew W.; Neeves, Keith B.
2015-01-01
Fibrin is a biopolymer that gives thrombi the mechanical strength to withstand the forces imparted on them by blood flow. Importantly, fibrin is highly extensible, but strain hardens at low deformation rates. The density of fibrin in clots, especially arterial clots, is higher than that in gels made at plasma concentrations of fibrinogen (3–10 mg/mL), where most rheology studies have been conducted. Our objective in this study was to measure and characterize the elastic regimes of low (3–10 mg/mL) and high (30–100 mg/mL) density fibrin gels using shear and extensional rheology. Confocal microscopy of the gels shows that fiber density increases with fibrinogen concentration. At low strains, fibrin gels act as thermal networks independent of fibrinogen concentration. Within the low-strain regime, one can predict the mesh size of fibrin gels by the elastic modulus using semiflexible polymer theory. Significantly, this provides a link between gel mechanics and interstitial fluid flow. At moderate strains, we find that low-density fibrin gels act as nonaffine mechanical networks and transition to affine mechanical networks with increasing strains within the moderate regime, whereas high-density fibrin gels only act as affine mechanical networks. At high strains, the backbone of individual fibrin fibers stretches for all fibrin gels. Platelets can retract low-density gels by >80% of their initial volumes, but retraction is attenuated in high-density fibrin gels and with decreasing platelet density. Taken together, these results show that the nature of fibrin deformation is a strong function of fibrin fiber density, which has ramifications for the growth, embolization, and lysis of thrombi. PMID:25564864
NASA Astrophysics Data System (ADS)
Poley, L.; Bloch, I.; Edwards, S.; Friedrich, C.; Gregor, I.-M.; Jones, T.; Lacker, H.; Pyatt, S.; Rehnisch, L.; Sperlich, D.; Wilson, J.
2016-05-01
The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive used initially between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). However, this glue has several disadvantages, which motivated the search for an alternative. This paper presents a study of six ultra-violet (UV) cure glues and a glue pad for possible use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, thermal conduction and shear strength. Samples were thermally cycled, radiation hardness and corrosion resistance were also determined. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives than silver loaded glue. Results from electrical tests of first prototype modules constructed using these glues are presented.
Technical manual for manufacturing autologous fibrin tissue adhesive.
Park, J J; Cintron, J R; Siedentop, K H; Orsay, C P; Pearl, R K; Nelson, R L; Abcarian, H
1999-10-01
The aim of this article is to provide a concise and simple technical manual for manufacturing autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing for surgery. All materials and equipment needed to manufacture ethanol-based autologous fibrin tissue adhesive are listed. In addition, step-by-step instructions are provided to allow for easy and rapid fibrin adhesive production. Ethanol-based autologous fibrin tissue adhesive can be manufactured in under 60 minutes. Furthermore, at our institution the startup cost for manufacturing ethanol-based autologous fibrin tissue adhesive was under $2,500.00. Ethanol-based autologous fibrin tissue adhesive is a safe, reliable, and easily manufactured autologous fibrin tissue adhesive that can be made by a trained technician in any blood bank, pharmacy, or surgical laboratory.
Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment.
Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro
2016-03-24
The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.
Hatano, Junichi; Okuro, Kou; Aida, Takuzo
2016-01-04
PGlue(PZ), a pyrazoline (PZ)-based fluorescent adhesive which can be generated spatiotemporally in living systems, was developed. Since PGlue(PZ) carries many guanidinium ion (Gu(+)) pendants, it strongly adheres to various oxyanionic substrates through a multivalent salt-bridge interaction. PGlue(PZ) is given by bioorthogonal photopolymerization of a Gu(+)-appended monomer (Glue(TZ)), bearing tetrazole (TZ) and olefinic termini. Upon exposure to UV light, Glue(TZ) transforms into a nitrileimine (NI) intermediate (Glue(NI)), which is eligible for 1,3-dipolar polycycloaddition. However, Glue(NI) in aqueous media can concomitantly be deactivated into Glue(WA) by the addition of water, and the polymerization hardly occurs unless Glue(NI) is concentrated. We found that, even under high dilution, Glue(NI) is concentrated on oxyanionic substrates to a sufficient level for the polymerization, so that their surfaces can be point-specifically functionalized with PGlue(PZ) by the use of a focused beam of UV light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Bio-inspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair
Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Miranda-Nieves, David; Mu, Luye; Lin, Charles
2015-01-01
Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, we have developed a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate. Negatively charged alginate was used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ~30w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures. PMID:26227833
Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair.
Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Miranda Nieves, David; Mu, Luye; Langer, Robert S; Lin, Charles; Karp, Jeffrey M
2015-11-18
Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.
Rostagno, A A; Schwarzbauer, J E; Gold, L I
1999-03-01
Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the current studies, using proteolytic and recombinant proteins representing both the N- and C-terminal fibrin-binding regions, we localized and characterized the C-terminal fibrin-binding site, compared the relative fibrin-binding activities of both sites and determined the contribution of each site to the fibrin-binding activity of intact Fn. By fibrin-affinity chromatography, a protein composed of the 10F1 repeat through to the C-terminus of Fn (10F1-COOH), expressed in COS-1 cells, and 10F1-12F1, produced in Saccharomyces cerevisiae, displayed fibrin-binding activity. However, since 10F1 and 10F1.11F1 were not active, the presence of 12F1 is required for fibrin binding. A proteolytic fragment of 14.4 kDa, beginning 14 residues N-terminal to 10F1, was isolated from the fibrin-affinity matrix. Radio-iodinated 14.4 kDa fibrin-binding peptide/protein (FBP) demonstrated a dose-dependent and saturable binding to fibrin-coated wells that was both competitively inhibited and reversed by unlabelled 14.4 kDa FBP. Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively. The higher fibrin-binding affinity of the N-terminus was substantiated by the ability of both a recombinant 4F1.5F1 and a monoclonal antibody (mAb) to this site to maximally inhibit biotinylated Fn binding to fibrin by 80%, and by blocking the 90% inhibitory activity of a polyclonal anti-Fn, by absorption with the 25.9 kDa FBP. We propose that whereas the N-terminal site appears to contribute to most of the binding activity of native Fn to fibrin, the specific binding of the C-terminal site may strengthen this interaction.
Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.
Rostagno, A A; Schwarzbauer, J E; Gold, L I
1999-01-01
Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the current studies, using proteolytic and recombinant proteins representing both the N- and C-terminal fibrin-binding regions, we localized and characterized the C-terminal fibrin-binding site, compared the relative fibrin-binding activities of both sites and determined the contribution of each site to the fibrin-binding activity of intact Fn. By fibrin-affinity chromatography, a protein composed of the 10F1 repeat through to the C-terminus of Fn (10F1-COOH), expressed in COS-1 cells, and 10F1-12F1, produced in Saccharomyces cerevisiae, displayed fibrin-binding activity. However, since 10F1 and 10F1.11F1 were not active, the presence of 12F1 is required for fibrin binding. A proteolytic fragment of 14.4 kDa, beginning 14 residues N-terminal to 10F1, was isolated from the fibrin-affinity matrix. Radio-iodinated 14.4 kDa fibrin-binding peptide/protein (FBP) demonstrated a dose-dependent and saturable binding to fibrin-coated wells that was both competitively inhibited and reversed by unlabelled 14.4 kDa FBP. Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively. The higher fibrin-binding affinity of the N-terminus was substantiated by the ability of both a recombinant 4F1.5F1 and a monoclonal antibody (mAb) to this site to maximally inhibit biotinylated Fn binding to fibrin by 80%, and by blocking the 90% inhibitory activity of a polyclonal anti-Fn, by absorption with the 25.9 kDa FBP. We propose that whereas the N-terminal site appears to contribute to most of the binding activity of native Fn to fibrin, the specific binding of the C-terminal site may strengthen this interaction. PMID:10024513
Biomaterials for Improved Wound Healing
2013-10-01
is silver sulphadiazine (SSD) [6-7]. SSD possesses a broad spectrum of activity against gram- positive and gram-negative bacteria as well as fungi [8... polyethylene glycol-based fibrin gel (PEGylated fibrin gel) induces vasculogenesis both in vitro and in vivo [20]. To exploit the inherent ability of fibrin as...Loaded Chitosan Microspheres Impregnated in Polyethylene Glycol Fibrin Gels (SSD-CSM-PEGylated fibrin gels) and Adipose Derived Stem Cells embedded
Thelwell, Craig; Williams, Stella C.; Silva, Marta M. C. G.; Szabó, László; Kolev, Krasimir
2011-01-01
Regulation of tissue-type plasminogen activator (tPA) depends on fibrin binding and fibrin structure. tPA structure/function relationships were investigated in fibrin formed by high or low thrombin concentrations to produce a fine mesh and small pores, or thick fibers and coarse structure, respectively. Kinetics studies were performed to investigate plasminogen activation and fibrinolysis in the 2 types of fibrin, using wild-type tPA (F-G-K1-K2-P, F and K2 binding), K1K1-tPA (F-G-K1-K1-P, F binding), and delF-tPA (G-K1-K2-P, K2 binding). There was a trend of enzyme potency of tPA > K1K1-tPA > delF-tPA, highlighting the importance of the finger domain in regulating activity, but the differences were less apparent in fine fibrin. Fine fibrin was a better surface for plasminogen activation but more resistant to lysis. Scanning electron and confocal microscopy using orange fluorescent fibrin with green fluorescent protein-labeled tPA variants showed that tPA was strongly associated with agglomerates in coarse but not in fine fibrin. In later lytic stages, delF-tPA-green fluorescent protein diffused more rapidly through fibrin in contrast to full-length tPA, highlighting the importance of finger domain-agglomerate interactions. Thus, the regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time. PMID:20966169
Zhao, Wenxue; Han, Qianqian; Lin, Hang; Sun, Wenjie; Gao, Yuan; Zhao, Yannan; Wang, Bin; Wang, Xia; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu
2009-05-01
Appropriate three-dimensional (3D) scaffolds and signal molecules could accelerate tissue regeneration and wound repair. In this work, we targeted human basic fibroblast growth factor (bFGF), a potent angiogenic factor, to a fibrin scaffold to improve therapeutic angiogenesis. We fused bFGF to the Kringle4 domain (K4), a fibrin-binding peptide from human plasminogen, to endow bFGF with specific fibrin-binding ability. The recombinant K4bFGF bound specifically to the fibrin scaffold so that K4bFGF was delivered in a site-specific manner, and the fibrin scaffold provided 3D support for cell migration and proliferation. Subcutaneous implantation of the fibrin scaffolds bound with K4bFGF but not with bFGF induced neovascularization. Immunohistochemical analysis showed significantly more proliferation cells in the fibrin scaffolds incorporated with K4bFGF than in those with bFGF. Moreover, the regenerative tissues were integrated well with the fibrin scaffolds, suggesting its good biocompatibility. In summary, targeted delivery of K4bFGF could potentially improve therapeutic angiogenesis.
In-situ AFM measurement of single fibrin fiber stiffness before and after addition of Factor XIII
NASA Astrophysics Data System (ADS)
Houser, John; O'Brien, E. Timothy; Lord, Susan T.; Superfine, Richard; Falvo, Michael R.
2008-10-01
Fibrin fibers are the main structural component of blood clots. Ligation of fibrin by native Factor XIII (FXIII) serves to fine tune the mechanical properties of the clot. Mechanical alteration is important because a clot must be stiff enough to resist forces from blood flow but compliant enough to prevent embolism (fracture). Cone and Plate measurements of fibrin gels, which represent the vast majority of mechanical measurements on fibrin, show that FXIII increases clot stiffness. More recently, measurements on individual fibrin fibers show that they exhibit remarkable extensibility, breaking at strains up to 300%. As of yet, the origin of this extensibility is not fully understood. The different responses of ligated and unligated fibrin fibers can give us clues as to it's mechanism of extension. We use a combined fluorescence/atomic force microscope to stretch individual, isolated, fibrin fibers and then compare force extension curves of the same fiber before and after addition of FXIII. We found up to a 3.5-fold increase in fiber stiffness after addition of FXIII. We also show stiffening of individual fibrin fibers after crosslinking by gluteraldehyde.
Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment
Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro
2016-01-01
The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma. PMID:27009516
Research on preparation of phosphate-modified animal glue binder for foundry use
NASA Astrophysics Data System (ADS)
Wang, Tian-Shu; Liu, Wei-Hua; Li, Ying-Min
2018-03-01
In this paper, three phosphates were used as modifiers to modify animal glue binder. The structural characteristics and thermal properties of animal glue binder treated with phosphates were studied by Fourier transform-infrared spectroscopy, gel permeation chromatography and derivative thermogravimetric analysis. The results showed that the modified animal glue binder had better sand tensile strength and lower viscosity than untreated animal glue binder. The best modification process was as follows: the optimal amount of sodium carbonate was 4 wt% to animal glue; the optimal weight ratio of the modifiers was sodium pyrophosphate : sodium tripolyphosphate : sodium hexametaphosphate : animal glue = 3 : 3 : 4 : 100, and the optimal reaction should be performed at 80°C for a reaction time of 120 min. A final tensile strength of approximately 3.20 MPa was achieved and the viscosity value was approximately 880 mPa s.
Sylman, Joanna L; Daalkhaijav, Uranbileg; Zhang, Ying; Gray, Elliot M; Farhang, Parsa A; Chu, Tiffany T; Zilberman-Rudenko, Jevgenia; Puy, Cristina; Tucker, Erik I; Smith, Stephanie A; Morrissey, James H; Walker, Travis W; Nan, Xiaolin L; Gruber, András; McCarty, Owen J T
2017-05-01
In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation. Fibrin formation was initiated with tissue factor, ellagic acid (EA), or LC polyP in the presence of inhibitors of FXI and FXII. Our data demonstrated that inhibition of FXI decreased the rate of fibrin formation and fiber network density, and increased the fibrin network strength and rate of fibrinolysis when gelation was initiated via the contact activation pathway with EA. FXII inhibition decreased the fibrin formation and fibrin density, and increased the fibrinolysis rate only when fibrin formation was initiated via the contact activation pathway with LC polyP. Overall, we demonstrate that inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin.
Safety of Synthetic Glue Used for Laparoscopic Prolapse Treatment.
Sarasa Castelló, Núria; Toth, Alexandra; Canis, Michel; Botchorishvilli, Revaz
2017-12-29
We detected mesh erosion and serious postoperative complications in 3 women after performing laparoscopic promontofixation (LPF) using glue for mesh fixation. Glue, largely used in hernia surgery repair, is proposed by some gynecologic surgeons because it saves time and is easier to use than traditional sutures. We report 3 cases of postoperative complications after LPF in which glue had been used and provide research in the published literature about the use of glue in LPF. A research of glue use in gynecology mesh fixation was performed through PubMed on October 2016. The search was done using the Medical Subject Heading terms "POP" & "Laparoscopy" & "surgical Mesh" and the word either "glue" or "adhesive. Only 2 articles were found: Willecocq et al [1] and Estrade et al [2]. Neither study focused on postoperative complications. In this publication, we accurately edited video surgeries with an instructive purpose. University Hospital of Clermont-Ferrand, France. Patient A, a 65-year-old woman, complained of pelvic pain and vaginal discharge 1 month after LPF (polypropylene mesh and glue had been used). Wall mesh exposure and purulent discharge were noted. She received antibiotics and underwent mesh ablation surgery; debris of the glue was easily identified. Patient B, a 65-year-old lady with previous hysterectomy consulted for a bulging feeling in her vagina (classification: cystocele +2; rectocele +3 stage). An LPF was performed using polypropylene soft nonabsorbable mesh and glue. One month later, an apical defect of vaginal epithelialization was detected; she received long estrogenic local treatment but had to undergo surgery when presenting malodorous discharge and mesh exposure. The exposed mesh was removed, and pieces of glue were identified, having avoided mesh attachment. Patient C had a previous abdominal hysterectomy and promontofixation using a polyester mesh with glue. She consulted to us for vaginal mesh erosion covered with purulent discharge 3.5 years after LPF in another center. At the surgery, 1 cm of the prosthesis was identified in the vagina, dissected, and sutured. One year later, she consulted for dyspareunia and purulent discharge; vaginal rigid mesh exposure with an epithelization defect and inflammatory signs was seen. During laparoscopy, prosthetic exposition and glue debris on the prosthesis were identified. In all 3 cases, debris of glue were identified in the no integrated mesh area. The suggested reasons of exposure can be the excessive amount of surgical glue applied. Moreover, a large amount of glue may be impairing tissue ingrowth through the mesh pores, causing low fibrosis and poor tissue integration [3]. Glue seems to prevent fibrosis from occurring. Its use in pelvic organ prolapse laparoscopic mesh fixation should be done with caution. No prospective studies reporting long-term comorbidities and results have been published. Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.
Ahmann, Katherine A.; Weinbaum, Justin S.; Johnson, Sandra L.
2010-01-01
Completely biological tissue replacements can be fabricated by entrapping cells in a molded fibrin gel. Over time, the fibrin is degraded and replaced with cell-produced extracellular matrix. However, the relationship between fibrin degradation and matrix deposition has not been elucidated. We developed techniques to quantify fibrin degradation products (FDP) and examine plasmin activity in the conditioned medium from fibrin-based constructs. Fibrin-based tissue constructs fabricated with vascular smooth muscle cells (vSMC) were cultured for 5 weeks in the presence of varied concentrations of the fibrinolysis inhibitor ɛ-aminocaproic acid and cellularity, and deposited collagen and elastin were measured weekly. These data revealed that increasing concentrations of ɛ-aminocaproic acid led to delayed and diminished FDP production, lower vSMC proliferation, and decreased collagen and elastin deposition. FDP were shown to have a direct biological effect on vSMC cultures and vSMC within the fibrin-based constructs. Supplementing construct cultures with 250 or 500 μg/mL FDP led to 30% higher collagen deposition than the untreated controls. FDP concentrations as high as 250 μg/mL were estimated to exist within the constructs, indicating that FDP generation during remodeling of the fibrin-based constructs exerted direct biological activity. These results help explain many of the positive outcomes reported with fibrin-based tissue constructs in the literature, as well as demonstrate the importance of regulating plasmin activity during their fabrication. PMID:20536358
Starmans, Lucas W E; van Mourik, Tiemen; Rossin, Raffaella; Verel, Iris; Nicolay, Klaas; Grüll, Holger
2015-06-01
Fibrin deposition plays an important role in the formation of mature tumor stroma and provides a facilitating scaffold for tumor angiogenesis. This study investigates the potential of the (111)In-labeled fibrin-binding peptide EPep for SPECT imaging of intratumoral fibrin deposition. (111)In-EPep and negative control (111)In-NCEPep were synthesized and characterized in vitro. In vivo SPECT images and ex vivo biodistribution profiles and autoradiographs were obtained in a fibrin-rich BT-20 breast cancer mouse model. Furthermore, biodistribution profiles were obtained in the fibrin-poor MDA-MD-231 model. In vitro, (111)In-EPep displayed significantly more binding than (111)In-NCEPep toward human and mouse derived fibrin. SPECT/CT images displayed a marked SPECT signal in the tumor area for BT-20 tumor bearing mice injected with EPep but not for mice injected with NCEPep. Biodistribution profiles of BT-20 tumor bearing mice 3 h post-tracer injection showed significantly higher tumor uptake for EPep with respect to NCEPep (0.39 ± 0.14 and 0.11 ± 0.03% ID g(-1), respectively), whereas uptake in other organs was similar for EPep and NCEPep. Autoradiography of BT-20 tumor sections displayed a high signal for EPep which colocalized with intratumoral fibrin deposits. Histological evaluation of MDA-MB-231 tumor sections displayed no significant tumor stroma and only minute fibrin deposits. Biodistribution profiles in MDA-MB-231 tumor bearing mice 3 h post-injection showed EPep tumor uptake (0.14 ± 0.04% ID g(-1)) which was significantly lower with respect to EPep BT-20 tumor uptake, indicating fibrin-specificity of EPep tumoral uptake. In conclusion, this work demonstrates the potential of EPep SPECT imaging for visualization of tumoral fibrin deposition.
Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts
Rahman, Saeed Ur; Ryoo, Hyun-Mo
2017-01-01
Cementum is a mineralized layer on the tooth’s root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (−900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation. PMID:29120400
ERIC Educational Resources Information Center
Roy, Ken
2010-01-01
While glue guns are very useful, there are safety issues. Regardless of the temperature setting, glue guns can burn skin. The teacher should demonstrate and supervise the use of glue guns and have a plan should a student get burned. There should be an initial first aid protocol in place, followed by a visit to the school nurse. An accident report…
NASA Astrophysics Data System (ADS)
Barbosa, F.; Bessuille, J.; Chudakov, E.; Dzhygadlo, R.; Fanelli, C.; Frye, J.; Hardin, J.; Kelsey, J.; Patsyuk, M.; Schwarz, C.; Schwiening, J.; Stevens, J.; Shepherd, M.; Whitlatch, T.; Williams, M.
2017-12-01
The GlueX DIRC (Detection of Internally Reflected Cherenkov light) detector is being developed to upgrade the particle identification capabilities in the forward region of the GlueX experiment at Jefferson Lab. The GlueX DIRC will utilize four existing decommissioned BaBar DIRC bar boxes, which will be oriented to form a plane roughly 4 m away from the fixed target of the experiment. A new photon camera has been designed that is based on the SuperB FDIRC prototype. The full GlueX DIRC system will consist of two such cameras, with the first planned to be built and installed in 2017. We present the current status of the design and R&D, along with the future plans of the GlueX DIRC detector.
Park, Chan Ho; Oh, Joung-Hwan; Jung, Hong-Moon; Choi, Yoonnyoung; Rahman, Saeed Ur; Kim, Sungtae; Kim, Tae-Il; Shin, Hong-In; Lee, Yun-Sil; Yu, Frank H; Baek, Jeong-Hwa; Ryoo, Hyun-Mo; Woo, Kyung Mi
2017-10-01
Cementum formation on the exposed tooth-root surface is a critical process in periodontal regeneration. Although various therapeutic approaches have been developed, regeneration of integrated and functional periodontal complexes is still wanting. Here, we found that the OCCM30 cementoblasts cultured on fibrin matrix express substantial levels of matrix proteinases, leading to the degradation of fibrin and the apoptosis of OCCM30 cells, which was reversed upon treatment with a proteinase inhibitor, ε-aminocaproic acid (ACA). Based on these findings, ACA-releasing chitosan particles (ACP) were fabricated and ACP-incorporated fibrin (fibrin-ACP) promoted the differentiation of cementoblasts in vitro, as confirmed by bio-mineralization and expressions of molecules associated with mineralization. In a periodontal defect model of beagle dogs, fibrin-ACP resulted in substantial cementum formation on the exposed root dentin in vivo, compared to fibrin-only and enamel matrix derivative (EMD) which is used clinically for periodontal regeneration. Remarkably, the fibrin-ACP developed structural integrations of the cementum-periodontal ligament-bone complex by the Sharpey's fiber insertion. In addition, fibrin-ACP promoted alveolar bone regeneration through increased bone volume of tooth roof-of-furcation defects and root coverage. Therefore, fibrin-ACP can promote cementogenesis and osteogenesis by controlling biodegradability of fibrin, implicating the feasibility of its therapeutic use to improve periodontal regeneration. Cementum, the mineralized layer on root dentin surfaces, functions to anchor fibrous connective tissues on tooth-root surfaces with the collagenous Sharpey's fibers integration, of which are essential for periodontal functioning restoration in the complex. Through the cementum-responsible fiber insertions on tooth-root surfaces, PDLs transmit various mechanical responses to periodontal complexes against masticatory/occlusal stimulations to support teeth. In this study, periodontal tissue regeneration was enhanced by use of modified fibrin biomaterial which significantly promoted cementogenesis within the periodontal complex with structural integration by collagenous Sharpey's fiber insertions in vivo by controlling fibrin degradation and consequent cementoblast apoptosis. Furthermore, the modified fibrin could improve repair and regeneration of tooth roof-of-furcation defects, which has spatial curvatures and geometrical difficulties and hardly regenerates periodontal tissues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen/fibrin degradation products assay. 864.7320 Section 864.7320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....7320 Fibrinogen/fibrin degradation products assay. (a) Identification. A fibrinogen/fibrin degradation...
The Non-catalytic B Subunit of Coagulation Factor XIII Accelerates Fibrin Cross-linking*
Souri, Masayoshi; Osaki, Tsukasa; Ichinose, Akitada
2015-01-01
Covalent cross-linking of fibrin chains is required for stable blood clot formation, which is catalyzed by coagulation factor XIII (FXIII), a proenzyme of plasma transglutaminase consisting of catalytic A (FXIII-A) and non-catalytic B subunits (FXIII-B). Herein, we demonstrate that FXIII-B accelerates fibrin cross-linking. Depletion of FXIII-B from normal plasma supplemented with a physiological level of recombinant FXIII-A resulted in delayed fibrin cross-linking, reduced incorporation of FXIII-A into fibrin clots, and impaired activation peptide cleavage by thrombin; the addition of recombinant FXIII-B restored normal fibrin cross-linking, FXIII-A incorporation into fibrin clots, and activation peptide cleavage by thrombin. Immunoprecipitation with an anti-fibrinogen antibody revealed an interaction between the FXIII heterotetramer and fibrinogen mediated by FXIII-B and not FXIII-A. FXIII-B probably binds the γ-chain of fibrinogen with its D-domain, which is near the fibrin polymerization pockets, and dissociates from fibrin during or after cross-linking between γ-chains. Thus, FXIII-B plays important roles in the formation of a ternary complex between proenzyme FXIII, prosubstrate fibrinogen, and activator thrombin. Accordingly, congenital or acquired FXIII-B deficiency may result in increased bleeding tendency through impaired fibrin stabilization due to decreased FXIII-A activation by thrombin and secondary FXIII-A deficiency arising from enhanced circulatory clearance. PMID:25809477
Hickerson, William L; Nur, Israel; Meidler, Roberto
2011-01-01
The objective of the present study was to compare the mechanical, kinetic, and biochemical properties of fibrin clots produced using EVICEL Fibrin Sealant (Human) and TISSEEL Fibrin Sealant. The stiffness/elasticity and strength of fibrin clots formed with EVICEL and TISSEEL were assessed using applied mechanical force and thromboelastography (TEG). The factor XIII content of the fibrin clots was also evaluated. Mean Young modulus and tensile strength of the fibrin clots produced by EVICEL were significantly higher than those of clots produced by TISSEEL (P < 0.05 for both). The mean time to initial clot formation and mean time to the predefined level of clot formation were numerically shorter for EVICEL compared with TISSEEL. Furthermore, mean maximal amplitude of the clots formed with EVICEL was significantly greater than that for the clots formed with TISSEEL. Mean concentration of factor XIII for the EVICEL fibrinogen samples tested was 9 IU/ml compared with undetectable concentrations of factor XIII for the TISSEEL fibrinogen samples. Fibrin clots formed with EVICEL have a much higher resistance to stretching and tensile strength and are more capable of maintaining their structure against applied force than those formed with TISSEEL. EVICEL also allows more rapid development of fibrin clots than TISSEEL. This superior clot strength and resilience obtained with EVICEL relative to TISSEEL may be due in large part to the presence of factor XIII.
Fibrin Formation, Structure and Properties
Weisel, John W.; Litvinov, Rustem I.
2017-01-01
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin. PMID:28101869
Evidence from Multiple Species that Spider Silk Glue Component ASG2 is a Spidroin
Collin, Matthew A.; Clarke, Thomas H.; Ayoub, Nadia A.; Hayashi, Cheryl Y.
2016-01-01
Spiders in the superfamily Araneoidea produce viscous glue from aggregate silk glands. Aggregate glue coats prey-capture threads and hampers the escape of prey from webs, thereby increasing the foraging success of spiders. cDNAs for Aggregate Spider Glue 1 (ASG1) and 2 (ASG2) have been previously described from the golden orb-weaver, Nephila clavipes, and Western black widow, Latrodectus hesperus. To further investigate aggregate glues, we assembled ASG1 and ASG2 from genomic target capture libraries constructed from three species of cob-web weavers and three species of orb-web weavers, all araneoids. We show that ASG1 is unlikely to be a glue, but rather is part of a widespread arthropod gene family, the peritrophic matrix proteins. For ASG2, we demonstrate its remarkable architectural and sequence similarities to spider silk fibroins, indicating that ASG2 is a member of the spidroin gene family. Thus, spidroins have diversified into glues in addition to task-specific, high performance fibers. PMID:26875681
Spiders Tune Glue Viscosity to Maximize Adhesion.
Amarpuri, Gaurav; Zhang, Ci; Diaz, Candido; Opell, Brent D; Blackledge, Todd A; Dhinojwala, Ali
2015-11-24
Adhesion in humid conditions is a fundamental challenge to both natural and synthetic adhesives. Yet, glue from most spider species becomes stickier as humidity increases. We find the adhesion of spider glue, from five diverse spider species, maximizes at very different humidities that matches their foraging habitats. By using high-speed imaging and spreading power law, we find that the glue viscosity varies over 5 orders of magnitude with humidity for each species, yet the viscosity at maximal adhesion for each species is nearly identical, 10(5)-10(6) cP. Many natural systems take advantage of viscosity to improve functional response, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic organic salts that determines water uptake in the glue. We therefore anticipate that manipulation of polymer-salts interaction to control viscosity can provide a simple mechanism to design humidity responsive smart adhesives.
Barbosa, F.; Bessuille, J.; Chudakov, E.; ...
2017-02-03
We present the GlueX DIRC (Detection of Internally Reflected Cherenkov light) detector that is being developed to upgrade the particle identification capabilities in the forward region of the GlueX experiment at Jefferson Lab. The GlueX DIRC will utilize four existing decommissioned BaBar DIRC bar boxes, which will be oriented to form a plane roughly 4 m away from the fixed target of the experiment. A new photon camera has been designed that is based on the SuperB FDIRC prototype. The full GlueX DIRC system will consist of two such cameras, with the first planned to be built and installed inmore » 2017. In addition, we present the current status of the design and R&D, along with the future plans of the GlueX DIRC detector.« less
Gallet, B; Zemour, G; Saudemont, J P; Renard, P; Hillion, M L; Hiltgen, M
1995-01-01
Systemic embolism is an unusual complication of endoscopic obturation of gastroesophageal varices with glue. This report describes a case of cerebral embolism after this procedure. Intracardiac glue within the left atrium was demonstrated by echocardiography. Cardiac fluoroscopy demonstrated an abnormal vessel connecting periesophageal veins with the right upper pulmonary vein. Cardiac surgery was performed. Intracardiac glue was removed and the entering orifice of the abnormal vessel in the right upper pulmonary vein was sutured. To our knowledge, this is the first reported case of intracardiac glue after variceal obturation. Echocardiography is useful in the diagnosis of this rare complication.
Bidault, Laurent; Deneufchatel, Marie; Vancaeyzeele, Cédric; Fichet, Odile; Larreta-Garde, Véronique
2013-11-11
A fibrin hydrogel at physiological concentration (5 mg/mL) was associated with polyvinyl alcohol (PVA) inside an interpenetrating polymer networks (IPN) architecture. Previously, PVA has been modified with methacrylate functions in order to cross-link it by free-radical polymerization. The fibrin network was synthesized by the enzymatic hydrolysis of fibrinogen by thrombin. The resulting self-supported materials simultaneously exhibit the properties of the fibrin hydrogel and those of the synthetic polymer network. Their storage modulus is 50-fold higher than that of the fibrin hydrogel and they are completely rehydratable. These materials are noncytotoxic toward human fibroblast and the fibrin present on the surface of PVAm-based IPNs favors cell development.
The effect of fibrin on cultured vascular endothelial cells.
Kadish, J L; Butterfield, C E; Folkman, J
1979-01-01
The normal cobblestone monolayer architecture of cultured vascular endothelium becomes rapidly disorganized after contact of the cell layer with a fibrin clot. The cells of a confluent endothelial monolayer separate into individual migratory cells in 4--6 hr after contact with fibrin. The effect is reversible in that removal of the fibrin clot results in resumption of the normal morphology within about 2 hr. No other cell type tested exhibits the same change in organization when exposed to fibrin. A similar morphological change in endothelium does occur after the cell layer is overlaid with a collagen fibril gel but a gel of methylcellulose has no effect. It is proposed that the change in behavior of endothelial cells in response to contact with fibrin may represent a cellular component of fibrinolysis. The implications of this finding for the pathophysiology of disease states involving intravascular fibrin deposition are discussed.
Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.
Zubairova, Laily D; Nabiullina, Roza M; Nagaswami, Chandrasekaran; Zuev, Yuriy F; Mustafin, Ilshat G; Litvinov, Rustem I; Weisel, John W
2015-12-04
Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.
Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots
Zubairova, Laily D.; Nabiullina, Roza M.; Nagaswami, Chandrasekaran; Zuev, Yuriy F.; Mustafin, Ilshat G.; Litvinov, Rustem I.; Weisel, John W.
2015-01-01
Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis. PMID:26635081
Houser, John R; Hudson, Nathan E; Ping, Lifang; O'Brien, E Timothy; Superfine, Richard; Lord, Susan T; Falvo, Michael R
2010-11-03
Fibrin fibers form the structural scaffold of blood clots and perform the mechanical task of stemming blood flow. Several decades of investigation of fibrin fiber networks using macroscopic techniques have revealed remarkable mechanical properties. More recently, the microscopic origins of fibrin's mechanics have been probed through direct measurements on single fibrin fibers and individual fibrinogen molecules. Using a nanomanipulation system, we investigated the mechanical properties of individual fibrin fibers. The fibers were stretched with the atomic force microscope, and stress-versus-strain data was collected for fibers formed with and without ligation by the activated transglutaminase factor XIII (FXIIIa). We observed that ligation with FXIIIa nearly doubled the stiffness of the fibers. The stress-versus-strain behavior indicates that fibrin fibers exhibit properties similar to other elastomeric biopolymers. We propose a mechanical model that fits our observed force extension data, is consistent with the results of the ligation data, and suggests that the large observed extensibility in fibrin fibers is mediated by the natively unfolded regions of the molecule. Although some models attribute fibrin's force-versus-extension behavior to unfolding of structured regions within the monomer, our analysis argues that these models are inconsistent with the measured extensibility and elastic modulus. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Mondal, Nandan Kumar; Ghosh, Sreenita; Ray, Manas Ranjan
2011-04-03
Genotoxicity of glue sniffing/huffing and tobacco use has been examined in 302 street boys (median age 13 years) and 50 age-matched control school boys who were neither tobacco nor glue users. All the street boys were tobacco users. In addition, 155 were addicted to gasp an industrial adhesive popularly known as 'Golden glue'. Micronucleus (MN) frequency was determined as a measure of chromosomal breakage in exfoliated buccal epithelial cells (BECs) and DNA double strand breaks were quantitatively assessed by counting γ-H2AX foci using immunofluorescence microscopy. Micronucleated cell frequencies (MCFs) in BEC of glue non-addicted (only tobacco) and addicted (tobacco plus glue) street boys were 1.87 ± 1.06‰ and 4.04 ± 2.55‰ respectively, which were significantly higher than that of control (0.32 ± 0.11‰, p<0.0001). Similarly, the numbers γ-H2AX foci in nuclei of BEC were 2.3- and 5.2-times more than control in glue non-addicted and addicted street boys respectively (p<0.0001). Spearman's rank correlation revealed a strong positive association between years of glue addiction with MCFs and γ-H2AX foci numbers, and the association between glue addiction and chromosomal and DNA damage remained positive and significant after controlling income, spending on addiction and loss of appetite as potential confounders in multivariate logistic regression analysis. Thus, addiction to tobacco among the street children in India is associated with chromosomal and DNA damage in BECs and the severity of these changes is significantly increased by the habit of sniffing/huffing of industrial glue. Copyright © 2011 Elsevier B.V. All rights reserved.
SAZONOVA, I. Y.; MCNAMEE, R. A.; HOUNG, A. K.; KING, S. M.; HEDSTROM, L.; REED, G. L.
2013-01-01
Summary Background: Given the worldwide epidemic of cardiovascular diseases, a more effective means of dissolving thrombi that cause heart attacks, could markedly reduce death, disability and healthcare costs. Plasminogen activators (PAs) such as streptokinase (SK) and tissue plasminogen activator (TPA) are currently used to dissolve fibrin thrombi. SK is cheaper and more widely available, but it appears less effective because it lacks TPA’s fibrin-targeted properties that focus plasminogen activation on the fibrin surface. Objective: We examined whether re-programming SK’s mechanism of action would create PAs with greater fibrin-targeting and potency than TPA. Methods and Results: When fibrinogen consumption was measured in human plasma, reprogrammed molecules SKΔ1 and SKΔ59 were 5-fold and > 119-fold more fibrin-dependent than SK (P < 0.0001), and 2-fold and > 50-fold more fibrin-dependent than TPA (P < 0.001). The marked fibrin-targeting of SKΔ59 was due to the fact that: (i) it did not generate plasmin in plasma, (ii) it was rapidly inhibited by α2-antiplasmin, and (iii) it only processed fibrin-bound plasminogen. To assess the fibrin-targeting and therapeutic potential of these PAs in vivo, a novel ‘humanized’ fibrinolysis model was created by reconstituting plasminogen-deficient mice with human plasminogen. When compared with TPA, SKΔ1 and SKΔ59 were 4-fold (P < 0.0001) and 2-fold (P < 0.003) more potent at dissolving blood clots in vivo, respectively, on a mass-dose basis and 2–3 logs more potent than TPA (P < 0.0001) when doses were calibrated by standard activity assays. Conclusion: These experiments suggest that reprogramming SK’s mechanism of action markedly enhances fibrin-targeting and creates, in comparison with TPA, activators with greater fibrinolytic potency. PMID:19566545
Sazonova, I Y; McNamee, R A; Houng, A K; King, S M; Hedstrom, L; Reed, G L
2009-08-01
Given the worldwide epidemic of cardiovascular diseases, a more effective means of dissolving thrombi that cause heart attacks, could markedly reduce death, disability and healthcare costs. Plasminogen activators (PAs) such as streptokinase (SK) and tissue plasminogen activator (TPA) are currently used to dissolve fibrin thrombi. SK is cheaper and more widely available, but it appears less effective because it lacks TPA's fibrin-targeted properties that focus plasminogen activation on the fibrin surface. We examined whether re-programming SK's mechanism of action would create PAs with greater fibrin-targeting and potency than TPA. When fibrinogen consumption was measured in human plasma, reprogrammed molecules SKDelta1 and SKDelta59 were 5-fold and > 119-fold more fibrin-dependent than SK (P < 0.0001), and 2-fold and > 50-fold more fibrin-dependent than TPA (P < 0.001). The marked fibrin-targeting of SKDelta59 was due to the fact that: (i) it did not generate plasmin in plasma, (ii) it was rapidly inhibited by alpha2-antiplasmin, and (iii) it only processed fibrin-bound plasminogen. To assess the fibrin-targeting and therapeutic potential of these PAs in vivo, a novel 'humanized' fibrinolysis model was created by reconstituting plasminogen-deficient mice with human plasminogen. When compared with TPA, SKDelta1 and SKDelta59 were 4-fold (P < 0.0001) and 2-fold (P < 0.003) more potent at dissolving blood clots in vivo, respectively, on a mass-dose basis and 2-3 logs more potent than TPA (P < 0.0001) when doses were calibrated by standard activity assays. These experiments suggest that reprogramming SK's mechanism of action markedly enhances fibrin-targeting and creates, in comparison with TPA, activators with greater fibrinolytic potency.
Cha, Han Gyu; Shin, Ho Seong; Kang, Moon Seok; Nam, Seung Min
2012-01-01
Background The most common complication of latissimus dorsi myocutaneous flap in breast reconstruction is seroma formation in the back. Many clinical studies have shown that fibrin sealant reduces seroma formation. We investigated any statistically significant differences in postoperative drainage and seroma formation when utilizing the fibrin sealant on the site of the latissimus dorsi myocutaneous flap harvested for immediate breast reconstruction after skin-sparing partial mastectomy. Methods A total of 46 patients underwent immediate breast reconstruction utilizing a latissimus dorsi myocutaneous island flap. Of those, 23 patients underwent the procedure without fibrin sealant and the other 23 were administered the fibrin sealant. All flaps were elevated with manual dissection by the same surgeon and were analyzed to evaluate the potential benefits of the fibrin sealant. The correlation analysis and Mann-Whitney U test were used for analyzing the drainage volume according to age, weight of the breast specimen, and body mass index. Results Although not statistically significant, the cumulative drainage fluid volume was higher in the control group until postoperative day 2 (530.1 mL compared to 502.3 mL), but the fibrin sealant group showed more drainage beginning on postoperative day 3. The donor site comparisons showed the fibrin sealant group had more drainage beginning on postoperative day 3 and the drain was removed 1 day earlier in the control group. Conclusions The use of fibrin sealant resulted in no reduction of seroma formation. Because the benefits of the fibrin sealant are not clear, the use of fibrin sealant must be fully discussed with patients before its use as a part of informed consent. PMID:23094246
Thrombin generation and fibrin formation under flow on biomimetic tissue factor-rich surfaces.
Onasoga-Jarvis, A A; Puls, T J; O'Brien, S K; Kuang, L; Liang, H J; Neeves, K B
2014-01-01
Blood flow regulates coagulation and fibrin assembly by controlling the rate of transport of zymogens, enzymes and plasma proteins to and from the site of an injury. The objective of this work was to define the hemodynamic conditions under which fibrin can form under flow on tissue factor (TF)-rich substrates. TF-coated silica beads (~ 800 nm) were patterned into 18-85-μm spots. Normal pooled plasma and factors VIII, IX and XI deficient plasmas were perfused over the beads coated with 0.08, 0.8 and 8 molecules-TF μm(-2) at shear rates of 50-1000 s(-1) . Fibrin deposition and thrombin generation were measured by fluorescence microscopy in a hydrodynamic focusing microfluidic device. Fibrin deposition was supported on patterned bead spots, but not planar TF substrates at the same surface TF concentration. There was a threshold spot size and a shear rate dependent TF concentration that was necessary to support fibrin polymerization. FVIII and FIX had minor effects on fibrin dynamics at 8 molecules-TF μm(-2) , but were essential at 0.8 molecules-TF μm(-2) . The absence of FXI influenced thrombin generation and fibrin deposition at both 0.8 and 8 molecules-TF μm(-2) . These results show that fibrin deposition requires perturbations in the flow field that protect reactions from dilution by flow under venous and arterial conditions. FVIII and FIX have a modest effect on fibrin deposition at high TF concentrations, but are necessary for fibrin deposition at low TF concentrations. FXI amplifies thrombin generation under flow at both low and high TF concentrations. © 2013 International Society on Thrombosis and Haemostasis.
Effect of fibrin sealant in positioning and stabilizing microvascular pedicle: A comparative study.
Kim, Jeong Tae; Kim, Youn Hwan; Kim, Sang Wha
2017-07-01
Fibrin sealants have had applications in hemostasis, cohesion, and promotion of healing in plastic surgery. In this article, we review cases where fibrin sealant was used to stabilize microvascular pedicles and compared with previous free flaps performed without fibrin sealant. Between 2008 and 2010, 62 consecutive patients underwent free tissue transfer for reconstruction; this involved 33 latissimus dorsi perforator flaps, 14 thoracodorsal artery perforator flaps, 9 latissimus dorsi myocutaneous flaps, 3 lateral thoracic artery perforator flaps, and 3 transverse rectus abdominis myocutaneous flaps, used in head and neck reconstruction, lower limb reconstructions, breast reconstructions, and facial palsy reconstruction. Following microvascular anastomosis, the microvascular pedicles were placed in the optimal position, and fibrin sealant was used to fix and stabilize them. The complications, such as venous thrombosis, arterial thrombosis, hematoma, and vascular pedicle kinking, were compared with that of 672 previous free flaps without fibrin sealant for stabilizing microvascular pedicles. Among the 62 free tissue transfers using fibrin sealant, there was only one complication involving flap failure (1.6%), in this case due to venous thrombosis. Analysis of 672 free flaps performed without application of fibrin sealant revealed 24 complications (3.6%), due to 3 venous thrombosis, 1 arterial thrombosis, 4 vascular pedicel compression due to hematoma, and 16 pedicle kinking. However, the comparison of complications between the free flap using fibrin sealant and the free flap without fibrin sealant were not statistically significant (P = 0.65). Fibrin sealant can be used to prevent vascular kinking and to position anastomosed vessels after successful micro-anastomosis and allow the reconstructive surgeon to overcome challenging situations of vascular pedicle related complications © 2016 Wiley Periodicals, Inc. Microsurgery 37:406-409, 2017. © 2016 Wiley Periodicals, Inc.
Fibrin structural and diffusional analysis suggests that fibers are permeable to solute transport.
Leonidakis, Kimon Alexandros; Bhattacharya, Pinaki; Patterson, Jennifer; Vos, Bart E; Koenderink, Gijsje H; Vermant, Jan; Lambrechts, Dennis; Roeffaers, Maarten; Van Oosterwyck, Hans
2017-01-01
Fibrin hydrogels are promising carrier materials in tissue engineering. They are biocompatible and easy to prepare, they can bind growth factors and they can be prepared from a patient's own blood. While fibrin structure and mechanics have been extensively studied, not much is known about the relation between structure and diffusivity of solutes within the network. This is particularly relevant for solutes with a size similar to that of growth factors. A novel methodological approach has been used in this study to retrieve quantitative structural characteristics of fibrin hydrogels, by combining two complementary techniques, namely confocal fluorescence microscopy with a fiber extraction algorithm and turbidity measurements. Bulk rheological measurements were conducted to determine the impact of fibrin hydrogel structure on mechanical properties. From these measurements it can be concluded that variations in the fibrin hydrogel structure have a large impact on the rheological response of the hydrogels (up to two orders of magnitude difference in storage modulus) but only a moderate influence on the diffusivity of dextran solutes (up to 25% difference). By analyzing the diffusivity measurements by means of the Ogston diffusion model we further provide evidence that individual fibrin fibers can be semi-permeable to solute transport, depending on the average distance between individual protofibrils. This can be important for reducing mass transport limitations, for modulating fibrinolysis and for growth factor binding, which are all relevant for tissue engineering. Fibrin is a natural biopolymer that has drawn much interest as a biomimetic carrier in tissue engineering applications. We hereby use a novel combined approach for the structural characterization of fibrin networks based on optical microscopy and light scattering methods that can also be applied to other fibrillar hydrogels, like collagen. Furthermore, our findings on the relation between solute transport and fibrin structural properties can lead to the optimized design of fibrin hydrogel constructs for controlled release applications. Finally, we provide new evidence for the fact that fibrin fibers may be permeable for solutes with a molecular weight comparable to that of growth factors. This finding may open new avenues for tailoring mass transport properties of fibrin carriers. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Evaluation of 111In-labeled EPep and FibPep as tracers for fibrin SPECT imaging.
Starmans, Lucas W E; van Duijnhoven, Sander M J; Rossin, Raffaella; Berben, Monique; Aime, Silvio; Daemen, Mat J A P; Nicolay, Klaas; Grüll, Holger
2013-11-04
Fibrin targeting is an attractive strategy for nuclear imaging of thrombosis, atherosclerosis and cancer. Recently, FibPep, an (111)In-labeled fibrin-binding peptide, was established as a tracer for fibrin SPECT imaging and was reported to allow sensitive detection of minute thrombi in mice using SPECT. In this study, we developed EPep, a novel (111)In-labeled fibrin-binding peptide containing the fibrin-binding domain of the clinically verified EP-2104R peptide, and sought to compare the potential of EPep and FibPep as tracers for fibrin SPECT imaging. In vitro, both EPep and FibPep showed high stability in serum, but were less stable in liver and kidney homogenate assays. Both peptide probes displayed comparable affinities toward human and mouse derived fibrin (Kd ≈ 1 μM), and similarly to FibPep, EPep showed fast blood clearance, low nontarget uptake and high thrombus uptake (6.8 ± 1.2% ID g(-1)) in a mouse carotid artery thrombosis model. Furthermore, EPep showed a similar affinity toward rat derived fibrin (Kd ≈ 1 μM), displayed high thrombus uptake in a rat carotid artery thrombosis model (0.74 ± 0.39% ID g(-1)), and allowed sensitive detection of thrombosis in rats using SPECT. In contrast, FibPep displayed a significantly lower affinity toward rat derived fibrin (Kd ≈ 14 μM) and low uptake in rat thrombi (0.06 ± 0.02% ID g(-1)) and did not allow clear visualization of carotid artery thrombosis in rats using SPECT. These results were confirmed ex vivo by autoradiography, which showed a 7-fold higher ratio of activity in the thrombus over the contralateral carotid artery for EPep in comparison to FibPep. These findings suggest that the FibPep binding fibrin epitope is not fully homologous between humans and rats, and that preclinical rat models of disease should not be employed to gauge the clinical potential of FibPep. In conclusion, both peptides showed approximately similar metabolic stability and affinity toward human and mouse derived fibrin, and displayed high thrombus uptake in a mouse carotid artery thrombosis model. Therefore, both EPep and FibPep are promising fibrin targeted tracers for translation into clinical settings to serve as novel tools for molecular imaging of fibrin.
Ugur, M G; Balat, O; Ozturk, E; Bekerecioglu, M; Dikensoy, E
2012-07-01
To discuss common pitfalls in diagnosis and management of distal vaginal agenesis, and summarize 10 years of experience among 11 patients using an interposition full-thickness graft and fibrin glue. Eleven patients with distal vaginal agenesis were evaluated and managed with an interposition full-thickness graft to bridge the gap between the upper vagina and the introitus. Associated renal abnormalities and complications including infection, total lack of skin graft take, stress urinary incontinence, partial graft loss, vaginal stricture and graft uptake were all investigated. The mean age of the patients was 12.91 (standard deviation 1.22) years. All patients had primary amenorrhoea, cryptomenorrhea, and cyclical or constant pelvic pain. None of the patients had associated urological abnormalities, and there were no cases of infection, total lack of skin graft take, stress urinary incontinence, partial graft loss or vaginal stricture. Graft uptake was 100% in 10 of the 11 patients. Four patients have subsequently married and report a satisfactory sex life. Accurate diagnosis of distal vaginal agenesis and careful pre-operative set-up, including evaluation of associated anomalies, bowel preparation, available vaginal stents and a multidisciplinary approach for the potential need for grafts, may be key to success. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
[Severe Bleeding from the Middle Ear Cavity after Myringotomy: Review Based on a Case Report].
Hofmann, Veit M; Niehues, Stefan M; Albers, Andreas E; Pudszuhn, Annett
2017-03-01
Report of a rare case of severe bleeding from the middle ear cavity after myringotomy. On the basis of the case report, the procedure for such bleeding is discussed in the context of the literature. A 6-year-old boy received a revision myringotomy in an ambulant setting. During the procedure a severe bleeding occurred. The external auditory canal was adequately packed. The patient was extubated and transferred to the clinic as an emergency. Computer tomography of the temporal bone showed the anatomical variant of a dehiscent high jugular bulb, which had been injured. Because no rebleeding occurred, the packing of the ear canal was removed and an explorative tympanoscopy was performed on the third postoperative day. When the tympanomeatal flap was lifted, the defect in the jugular bulb was found. The lesion was covered with Tutopatch ® pads and fibrin glue and the auditory canal was packed again. After removal of the packing three weeks postoperatively a properly healed situs was found. No further measures were taken. The injury of a dehiscent jugular bulb in the course of ear surgeries leads to a massive hemorrhage. The case describes the diagnostic and therapeutic procedure for this relatively rare but severe complication. © Georg Thieme Verlag KG Stuttgart · New York.
MIDI face-lift and tricuspidal SMAS-flap.
Panfilov, Dimitrije E
2003-01-01
Looking tired is enough for many 40-50-years-olds to ask a plastic surgeon for prophylactic rejuvenation. They want to achieve good and long lasting effects with harmonious features, small scars, and--as they are still very active in their professional and private lives--a quick recovery is very important to them. We have developed a modification of the short-scar face-lift with solid deep support. We call it the MIDI face-lift. MIDI stands for Minimal, Invasive, Deep, Intensive. Technical details are as follows. Two half Z-plasties were performed at each end of modest skin excision, supra-auriculary and retro-auriculary, to avoid even suture edges. By doing so we achieve very unobtrusive scarring. For solid SMAS tension we perform SMAS-plication, simple SMAS-flap, or tricuspidal SMAS-flap. This is an overview of 200 patients we treated over three years. By applying tumescent local anesthesia with adrenaline and ornipressin, and fibrin glue at the end of the procedure, we can the draining so that 96% of our patients were outpatients. Technical details will be discussed as well as complications, adjuvant and alternative procedures. The satisfaction of our patients was high (88%) and no major complications have occurred. Only three out of 200 patients had to undergo revisionary surgery.
Villiger, P; Ryan, E A; Owen, R; O'Kelly, K; Oberholzer, J; Al Saif, F; Kin, T; Wang, H; Larsen, I; Blitz, S L; Menon, V; Senior, P; Bigam, D L; Paty, B; Kneteman, N M; Lakey, J R T; Shapiro, A M James
2005-12-01
Islet transplantation is being offered increasingly for selected patients with unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need for surgery, but is associated with potential risk of bleeding. Between 1999 and 2005, we performed 132 percutaneous transhepatic islet transplants in 67 patients. We encountered bleeding in 18/132 cases (13.6%). In univariate analysis, the risk of bleeding in the absence of effective track ablation was associated with an increasing number of procedures (2nd and 3rd procedures with an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR 4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45 U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A multivariate analysis further confirmed the cumulative transplant procedure number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk factors for bleeding. Effective mechanical sealing of the intrahepatic portal catheter tract with thrombostatic coils and tissue fibrin glue completely prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude that bleeding after percutaneous islet implantation is an avoidable complication provided the intraparenchymal liver tract is sealed effectively.
Adhesion modulation using glue droplet spreading in spider capture silk
Zhang, Ci; Blackledge, Todd A.
2017-01-01
Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture spiral silk is composed of an axial fibre of flagelliform silk covered with glue droplets that are arranged in a beads-on-a-string morphology that allows multiple droplets to simultaneously extend and resist pull off. Previous studies showed that the adhesion of capture silk is responsive to environmental humidity, increasing up to an optimum humidity that varied among different spider species. The maximum adhesion was hypothesized to occur when the viscoelasticity of the glue optimized contributions from glue spreading and bulk cohesion. In this study, we show how glue droplet shape during peeling contributes significantly to capture silk adhesion. Both overspreading and underspreading of glue droplets reduces adhesion through changes in crack propagation and failure regime. Understanding the mechanism of stimuli-responsive adhesion of spider capture silk will lead to new designs for smarter adhesives. PMID:28490605
Adhesion modulation using glue droplet spreading in spider capture silk.
Amarpuri, Gaurav; Zhang, Ci; Blackledge, Todd A; Dhinojwala, Ali
2017-05-01
Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture spiral silk is composed of an axial fibre of flagelliform silk covered with glue droplets that are arranged in a beads-on-a-string morphology that allows multiple droplets to simultaneously extend and resist pull off. Previous studies showed that the adhesion of capture silk is responsive to environmental humidity, increasing up to an optimum humidity that varied among different spider species. The maximum adhesion was hypothesized to occur when the viscoelasticity of the glue optimized contributions from glue spreading and bulk cohesion. In this study, we show how glue droplet shape during peeling contributes significantly to capture silk adhesion. Both overspreading and underspreading of glue droplets reduces adhesion through changes in crack propagation and failure regime. Understanding the mechanism of stimuli-responsive adhesion of spider capture silk will lead to new designs for smarter adhesives. © 2017 The Author(s).
Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*
Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas
2014-01-01
Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443
The disulfide isomerase ERp57 is required for fibrin deposition in vivo.
Zhou, J; Wu, Y; Wang, L; Rauova, L; Hayes, V M; Poncz, M; Essex, D W
2014-11-01
ERp57 is required for platelet function; however, whether ERp57 contributes to fibrin generation is unknown. Using an inhibitory anti-ERp57 antibody (mAb1), Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice, and mutants of ERp57, we analyzed the function of ERp57 in laser-induced thrombosis. Fibrin deposition was decreased in Pf4-Cre/ERp57(fl/fl) mice, consistent with a role for platelet ERp57 in fibrin generation. Fibrin deposition was further decreased with infusion of mAb1 and in Tie2-Cre/ERp57(fl/fl) mice, consistent with endothelial cells also contributing to fibrin deposition. Infusion of eptibifatide inhibited platelet and fibrin deposition, confirming a role for platelets in fibrin deposition. Infusion of recombinant ERp57 corrected the defect in fibrin deposition but not platelet accumulation, suggesting a direct effect of ERp57 on coagulation. mAb1 inhibited thrombin generation in vitro, consistent with a requirement for ERp57 in coagulation. Platelet accumulation was decreased to similar extents in Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice and normal mice infused with mAb1. Infusion of completely inactivated ERp57 or ERp57 with a non-functional second active site inhibited fibrin deposition and platelet accumulation, indicating that the isomerase activity of the second active site is required for these processes. ERp57 regulates thrombosis via multiple targets. © 2014 International Society on Thrombosis and Haemostasis.
Yokota, M; Basi, D L; Herzberg, M C; Meyer, M W
2001-01-01
In Streptococcus sanguinis (sanguis) induced experimental endocarditis, we sought evidence that the development of aortic valvular vegetation depends on the availability of fibrin. Endocarditis was induced in New Zealand white rabbits by catheter placement into the left ventricle and inoculation of the bacteria. Fibrin was localized in the developing vegetation with 99mTechnetium (Tc)-labeled anti-fibrin antibody one or three days later. When rabbit anti-fibrin antibody was given intravenously on day 1, the mass of aortic valvular vegetation was significantly reduced at day 3; infusion of non-specific rabbit IgG showed no effect. The 99mTc-labeled anti-fibrin antibody also labeled kidneys that showed macroscopic subcapsular hemorrhage. To learn if the deposition of fibrin in the kidneys was a consequence of endocarditis required a comparison of farm-bred and specific pathogen-free rabbits before and after the induction of endocarditis. Before induction, the kidneys of farm-bred rabbits were labeled, but specific pathogen-free rabbits were free of labeling and signs of macroscopic hemorrhage. After 3 days of endocarditis, kidneys of 10 of 14 specific pathogen-free rabbits labeled with 99mTc-labeled anti-fibrin antibody and showed hemorrhage. Kidney lesions were suggested to be a frequent sequellae of S. sanguinis infective endocarditis. For the first time, fibrin was shown to be required for the continued development of aortic valvular vegetations.
Bacakova, Marketa; Pajorova, Julia; Stranska, Denisa; Hadraba, Daniel; Lopot, Frantisek; Riedel, Tomas; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie
2017-01-01
Protein-coated resorbable synthetic polymeric nanofibrous membranes are promising for the fabrication of advanced skin substitutes. We fabricated electrospun polylactic acid and poly(lactide- co -glycolic acid) nanofibrous membranes and coated them with fibrin or collagen I. Fibronectin was attached to a fibrin or collagen nanocoating, in order further to enhance the cell adhesion and spreading. Fibrin regularly formed a coating around individual nanofibers in the membranes, and also formed a thin noncontinuous nanofibrous mesh on top of the membranes. Collagen also coated most of the fibers of the membrane and randomly created a soft gel on the membrane surface. Fibronectin predominantly adsorbed onto a thin fibrin mesh or a collagen gel, and formed a thin nanofibrous structure. Fibrin nanocoating greatly improved the attachment, spreading, and proliferation of human dermal fibroblasts, whereas collagen nanocoating had a positive influence on the behavior of human HaCaT keratinocytes. In addition, fibrin stimulated the fibroblasts to synthesize fibronectin and to deposit it as an extracellular matrix. Fibrin coating also showed a tendency to improve the ultimate tensile strength of the nanofibrous membranes. Fibronectin attached to fibrin or to a collagen coating further enhanced the adhesion, spreading, and proliferation of both cell types.
Bacakova, Marketa; Pajorova, Julia; Stranska, Denisa; Hadraba, Daniel; Lopot, Frantisek; Riedel, Tomas; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie
2017-01-01
Protein-coated resorbable synthetic polymeric nanofibrous membranes are promising for the fabrication of advanced skin substitutes. We fabricated electrospun polylactic acid and poly(lactide-co-glycolic acid) nanofibrous membranes and coated them with fibrin or collagen I. Fibronectin was attached to a fibrin or collagen nanocoating, in order further to enhance the cell adhesion and spreading. Fibrin regularly formed a coating around individual nanofibers in the membranes, and also formed a thin noncontinuous nanofibrous mesh on top of the membranes. Collagen also coated most of the fibers of the membrane and randomly created a soft gel on the membrane surface. Fibronectin predominantly adsorbed onto a thin fibrin mesh or a collagen gel, and formed a thin nanofibrous structure. Fibrin nanocoating greatly improved the attachment, spreading, and proliferation of human dermal fibroblasts, whereas collagen nanocoating had a positive influence on the behavior of human HaCaT keratinocytes. In addition, fibrin stimulated the fibroblasts to synthesize fibronectin and to deposit it as an extracellular matrix. Fibrin coating also showed a tendency to improve the ultimate tensile strength of the nanofibrous membranes. Fibronectin attached to fibrin or to a collagen coating further enhanced the adhesion, spreading, and proliferation of both cell types. PMID:28223803
Fibrinogen inhibits fibroblast-mediated contraction of collagen
Nien, Yih-Dar; Han, Yuan-Ping; Tawil, Bill; Chan, Linda S.; Tuan, Tai-Lan; Garner, Warren L.
2008-01-01
Extracellular matrix changes in composition and organization as it transitions from the provisional matrix of the fibrin/platelet plug to collagen scar in healed wounds. The manner in which individual matrix proteins affect these activities is not well established. In this article we describe the interactions of two important extracellular matrix components, fibrin and collagen, using an in vitro model of wound contraction, the fibroblast-populated collagen lattice. We utilized different fibrinogen sources and measured tissue reorganization in floating and tensioned collagen lattices. Our results showed that both fibrin and fibrinogen decreased the contraction of fibroblast populated collagen lattices in a dose-dependent manner. Polymerization of fibrinogen to fibrin using thrombin had no effect on this inhibition. Further, there was no effect due to changes in protein concentration, alternate components of the fibrin sealant, or the enzymatic action of thrombin. These results suggest that the initial stability of the fibrin provisional matrix is due to the fibrin, because this protein appears to inhibit contraction of the matrix. This may be important in the early phases of wound healing when clot stability is vital for hemostasis. Later, as fibrin is replaced by collagen, wound contraction can occur. PMID:12950643
Fibrin facilitates both innate and T cell-mediated defense against Yersinia pestis.1
Luo, Deyan; Lin, Shiuan; Parent, Michelle A.; Kanevsky, Isis Mullarky; Szaba, Frank M.; Kummer, Lawrence W.; Duso, Debra K.; Tighe, Michael; Hill, Jim; Gruber, Andras; Mackman, Nigel; Gailani, David; Smiley, Stephen T.
2013-01-01
The gram-negative bacterium Yersinia pestis causes plague, a rapidly progressing and often fatal disease. The formation of fibrin at sites of Y. pestis infection supports innate host defense against plague, perhaps by providing a non-diffusible spatial cue that promotes the accumulation of inflammatory cells expressing fibrin-binding integrins. This report demonstrates that fibrin is an essential component of T cell-mediated defense against plague but can be dispensable for antibody-mediated defense. Genetic or pharmacologic depletion of fibrin abrogated innate and T cell-mediated defense in mice challenged intranasally with Y. pestis. The fibrin-deficient mice displayed reduced survival, increased bacterial burden, and exacerbated hemorrhagic pathology. They also showed fewer neutrophils within infected lung tissue and reduced neutrophil viability at sites of liver infection. Depletion of neutrophils from wild type mice weakened T cell-mediated defense against plague. The data suggest that T cells combat plague in conjunction with neutrophils, which require help from fibrin in order to withstand Y. pestis encounters and effectively clear bacteria. PMID:23487423
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brown, Elvie; Hu, Dehong; Abu-Lail, Nehal
2013-02-19
Nanocrystalline cellulose, a new bio-nanomaterial is utilized as a reinforcing material for biocompatible fibrin matrix to form into a nanocomposite for small-diameter replacement vascular graft application (SDRVG). The periodate oxidation of NCC, which provided it with a reactive carbonyl group, allowed molecular interaction between NCC and fibrin. Such interaction resulted into an effective mechanical reinforcement indicated by the improvement of max. force, elongation at break and modulus when oxidized NCC (ONCC) was incorporated into fibrin. The nanocomposite’s mechanical properties can be manipulated to conform to the native blood vessel by varying the ONCC to fibrin ratio and/or by controlling themore » degree of oxidation of NCC. Using atomic force microscopy had provided fundamental information on the effects of molecular interactions to the nanolevel mechanical properties of NCC/fibrin nanocomposites. This fundamental information established the positive feasibility and commenced continuing investigation for the practical SDRVG application of NCC/fibrin nanocomposite.« less
Double Coaxial Microcatheter Technique for Glue Embolization of Renal Arteriovenous Malformations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Uchikawa, Yoko, E-mail: jauchikawa@gmail.com; Mori, Kensaku, E-mail: moriken@md.tsukuba.ac.jp; Shiigai, Masanari, E-mail: m-41gai@yahoo.co.jp
PurposeTo demonstrate the technical benefit of the double coaxial microcatheter technique for embolization of renal arteriovenous malformations (AVMs) with n-butyl cyanoacrylate and iodized oil (glue).Materials and MethodsSix consecutive patients (1 man and 5 women; mean age 61 years; range 44–77 years) with renal AVMs were included. Five patients had hematuria, and one had a risk of heart failure due to a large intrarenal arteriovenous shunt. All patients underwent transarterial embolization using glue and the double coaxial microcatheter technique with outer 2.6F and inner 1.9F microcatheters. After glue injection, the inner microcatheter was retracted, while the outer microcatheter was retained. We assessed themore » complications and clinical outcomes of this technique.ResultsTechnical success was achieved in all patients. In 9 sessions, 34 feeding arteries were embolized with glue using the double coaxial microcatheter technique, 1 was embolized with glue using a single microcatheter, and 2 were embolized with coils. The double coaxial microcatheter technique was useful for selecting small tortuous feeding arteries, preventing glue reflux to the proximal arteries, and approaching multiple feeding arteries without complete retraction of the microcatheters. As a minor complication, glue migrated into the venous system in four patients without any sequelae. In all patients, favorable clinical outcomes, including hematuria cessation in five patients and improvement of the large intrarenal arteriovenous shunt in one patient, were obtained without deterioration of renal function.ConclusionGlue embolization with the double coaxial microcatheter technique was useful for treating renal AVMs with multiple tortuous feeding arteries.« less
Scaffold architecture and fibrin gels promote meniscal cell proliferation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pawelec, K. M., E-mail: pawelec.km@gmail.com, E-mail: jw626@cam.ac.uk; Best, S. M.; Cameron, R. E.
2015-01-01
Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.
... with other blood proteins to form fibrin. Fibrin strands form a net that entraps more platelets and ... that is normally dissolved in blood, into long strands of fibrin that radiate from the clumped platelets ...
Kang, Ran; Li, Haisheng; Lysdahl, Helle; Quang Svend Le, Dang; Chen, Menglin; Xie, Lin; Bünger, Cody
2017-01-01
In an attempt to find an ideal closure method during annulus defect repair, we evaluate the use of medical glue by mechanical and biocompatible test. Cyanoacrylate medical glue was applied together with a multilayer microfiber/nanofiber polycaprolactone scaffold and suture in annulus repair. Continuous axial loading and fatigue mechanical test was performed. Furthermore, the in vitro response of mesenchymal stem cell (MSC) to the glue was evaluated by cell viability assay. The in vivo response of annulus tissue to the glue and scaffold was also studied in porcine lumbar spine; histological sections were evaluated after 3 months. Cyanoacrylate glue significantly improved the closure effect in the experimental group with failure load 2825.7 ± 941.6 N, compared to 774.1 ± 281.3 N in the control group without glue application (p < 0.01). The experimental group also withstood the fatigue test. No toxic effect was observed by in vitro cell culture and in vivo implantation. On the basis of this initial evaluation, the use of cyanoacrylate medical glue improves closure effect with no toxicity in annulus defect repair. This method of annulus repair merits further effectiveness study in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 14-20, 2017. © 2015 Wiley Periodicals, Inc.
Microporous nanofibrous fibrin-based scaffolds for craniofacial bone tissue engineering
NASA Astrophysics Data System (ADS)
Osathanon, Thanaphum
The fibrotic response of the body to synthetic polymers limits their success in tissue engineering and other applications. Though porous polymers have demonstrated improved healing, difficulty in controlling their pore sizes and pore interconnections has clouded the understanding of this phenomenon. In this study, a novel method to fabricate natural polymer/calcium phosphate composite scaffolds and immobilized alkaline phosphatase fibrin scaffolds with tightly controllable pore size, pore interconnection has been investigated. Microporous, nanofibrous fibrin scaffolds (FS) were fabricated using sphere-templating method. Calcium phosphate/fibrin composite scaffolds were created by solution deposition of calcium phosphate on fibrin surfaces or by direct incorporation of nanocrystalline hydroxyapatite (nHA). The SEM results showed that fibrin scaffolds exhibited a highly porous and interconnected structure. Osteoblast-like cells, obtained from murine calvaria, attached, spread and showed a polygonal morphology on the surface of the biomaterial. Multiple cell layers and fibrillar matrix deposition were observed. Moreover, cells seeded on mineralized fibrin scaffolds (MFS) exhibited significantly higher alkaline phosphatase activity as well as osteoblast marker gene expression compared to FS and nHA incorporated fibrin scaffolds (nHA/FS). These fibrin-based scaffolds were degraded both in vitro and in vivo. Furthermore, these scaffolds promoted bone formation in a mouse calvarial defect model and the bone formation was enhanced by addition of rhBMP-2. The second approach was to immobilize alkaline phosphatase (ALP) on fibrin scaffolds. ALP enzyme was covalently immobilized on the microporous nanofibrous fibrin scaffolds using 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (EDC). The SEM results demonstrated mineral deposition on immobilized ALP fibrin scaffolds (ALP/FS) when incubated in medium supplemented with beta-glycerophosphate, suggesting that the immobilized ALP enzyme was active. Mineral deposition was also observed in cells seeded on immobilized ALP/FS. Furthermore, cells seeded on immobilized ALP/FS exhibited higher osteoblast marker gene expression compared to those on control FS. Upon implantation in mouse calvarial defect, the immobilized ALP/FS treated group had slightly higher bone volume in the defect compared to empty defect control and FS alone. In conclusion, the enhanced biological responses both in vitro and in vivo demonstrated the potential application of these novel microporous nanofibrous fibrin-based scaffolds for bone tissue engineering.
Ming, Mo-yu; Cai, Shuang-qi; Chen, Yi-Qiang
2015-01-01
Background Pleural abrasion has been widely used to control the recurrence of primary spontaneous pneumothorax (PSP). However, controversy still exists regarding the advantages and disadvantages of pleural abrasion compared with other interventions in preventing the recurrence of PSP. Methods The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 15, 2014 to identify randomized controlled trials (RCTs) that compared the effects of pleural abrasion with those of other interventions in the treatment of PSP. The study outcomes included the PSP recurrence rate and the occurrence rate of adverse effects. Results Mechanical pleural abrasion and apical pleurectomy after thoracoscopic stapled bullectomy exhibited similarly persistent postoperative air leak occurrence rates (p = 0.978) and 1-year PSP recurrence rates (p = 0.821), whereas pleural abrasion led to reduced residual chest pain and discomfort (p = 0.001) and a smaller rate of hemothorax (p = 0.036) than did apical pleurectomy. However, the addition of minocycline pleurodesis to pleural abrasion did not reduce the pneumothorax recurrence rate compared with apical pleurectomy (3.8% for both procedures) but was associated with fewer complications. There was no statistical difference in the pneumothorax recurrence rate between mechanical pleural abrasion and chemical pleurodesis with minocycline on either an intention-to-treat basis (4 of 42 versus 0 of 42, p = 0.12; Fisher exact test) or after exclusions (2 of 40 versus 0 of 42, p = 0.24; Fisher exact test). Pleural abrasion plus minocycline pleurodesis also did not reduce the pneumothorax recurrence rate compared with pleural abrasion alone (p = 0.055). Moreover, pleural abrasion plus minocycline pleurodesis was associated with more intense acute chest pain. The postoperative overall recurrence rate in patients who underwent staple line coverage with absorbable cellulose mesh and fibrin glue was similar to that with mechanical abrasion after thoracoscopic bullectomy (13.8% vs. 14.2%, respectively; p = 0.555), but staple line coverage resulted in less postoperative residual pain than mechanical abrasion (0.4% vs.3.2%; p<0.0001). Pleural abrasion after thoracoscopic wedge resection did not decrease the recurrence of pneumothorax compared with wedge resection alone (p = 0.791), but the intraoperative bleeding and postoperative pleural drainage rates were higher when pleural abrasion was performed. Conclusions In addition to resulting in the same pneumothorax recurrence rate, thoracoscopic pleural abrasion with or without minocycline pleurodesis is safer than apical pleurectomy in the treatment of PSP. However, minocycline pleurodesis with or without pleural abrasion is not any more effective than pleural abrasion alone. Moreover, additional mechanical abrasion is not safer than additional staple line coverage with absorbable cellulose mesh and fibrin glue after thoracoscopic bullectomy because of increased postoperative pain. Additionally, pleural abrasion after thoracoscopic wedge resection should not be recommended for routine application due to the greater incidence of adverse effects than wedge resection alone. However, further large-scale, well-designed RCTs are needed to confirm the best procedure. PMID:26042737
Three-dimensional structure and cytokine distribution of platelet-rich fibrin.
Bai, Meng-Yi; Wang, Ching-Wei; Wang, Jyun-Yi; Lin, Ming-Fang; Chan, Wing P
2017-02-01
Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.
Stein-Merlob, Ashley F.; Kessinger, Chase W.; Erdem, S. Sibel; Zelada, Henry; Hilderbrand, Scott A.; Lin, Charles P.; Tearney, Guillermo J.; Jaff, Michael R.; Reed, Guy L.; Henke, Peter K.; McCarthy, Jason R.; Jaffer, Farouc A.
2015-01-01
Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies. PMID:26516370
Botnar, René M; Brangsch, Julia; Reimann, Carolin; Janssen, Christian H P; Razavi, Reza; Hamm, Bernd; Makowski, Marcus R
2018-05-30
The incidence of abdominal aortic aneurysms (AAAs) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of AAAs. This study evaluated the potential of a fibrin-specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of AAAs. AAAs spontaneously developed in ApoE -/- mice following the infusion of angiotensin-II (Ang-II, 1 μg/kg -1 ·per minute). An established fibrin-specific molecular MR probe (EP2104R, 10 μmol/kg -1 ) was administered after 1 to 4 weeks following Ang-II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (Philips Healthcare, Netherlands). The development of AAA-associated fibrin-rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high-resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast-to-noise-ratios (CNRs) and R1-relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry ( R 2 =0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy ( R 2 =0.78 and 0.72). The fibrin-specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced AAAs. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Biggerstaff, J; Amirkhosravi, A; Francis, J L
1997-10-01
Fibrin forms part of the stroma essential for growth of solid tumors. Anticoagulants reduce primary tumor growth and tumor metastasis in murine and some human tumors. These effects may be partly mediated by reduction of intra-tumor fibrin, although there are no quantitative data to support this hypothesis. We therefore evaluated the effect of warfarin on fibrin deposition in a subcutaneously (s.c.) implanted murine tumor using confocal laser scanning microscopy (CLSM). AJ mice received no treatment (n = 6) or sodium warfarin (3.5 mg/L in drinking water, n = 5). All animals received 2 x 10(6) syngeneic Neuro2a neuroblastoma cells s.c. After 14 days, primary tumors were excised and placed in liquid nitrogen. Warfarin treatment resulted in a small, but significant (P < 0.05), decrease in wet tumor weight. Frozen sections (20 microns) were incubated with goat anti-mouse fibrin(ogen) or normal goat serum (isotypic control) and stained with FITC-conjugated rabbit anti-goat antibody. Using a Multiprobe 2001 CLSM (Molecular Dynamics, Sunnyvale, CA), 20 serial optical sections were taken from five, randomly chosen, high power fields (60x objective) for each slide. A threshold excluded all fluorescence except that from structural components within the tumor stroma (fibrin). The volume of fibrin in each section series was determined, and the percentage of tumor volume occupied by fibrin calculated. Intra- and inter-assay variation were assessed on serial frozen tumor sections from an untreated animal. The percentage fibrin volume was not significantly different among or within experiments, indicating that the procedure was reproducible. In controls, the median (range) volume occupied by fibrin was 8.1% (2.4-22.3%), whereas in anticoagulated animals, this was reduced to 3.7% (0.4-14.0%; P < 0.001). This is the first quantitative demonstration that warfarin reduces fibrin deposition in solid tumors. We conclude that three-dimensional CLSM is useful for the quantitation of tissue antigens and that the technique may have clinical value.
Mendez, Julio J.; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum; Steinbacher, Derek M.; Leffell, David J.; Niklason, Laura E.
2014-01-01
Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608
Chronic glue sniffing with transient central hypothyroidism and hypergonadotropism.
Chen, Hua-Fen; Chen, Shwe-Winn; Chen, Peter; Su, Mei-Chin; See, Ting-Ting; Lee, Hsin-Yu
2003-12-01
Neuropsychiatric, gastrointestinal and muscular disorders associated with glue sniffing have been widely reported, but endocrinologic abnormalities of glue exposure are rarely mentioned in the literature. We report a 26-year old male patient, a chronic glue sniffer, who presented with weakness of both lower limbs. On physical examination, he had reduced muscle strength of his 4 limbs, especially in his lower limbs. Laboratory examination revealed hypokalemia with hyperchloremic metabolic acidosis. His thyroid function showed low TSH, T4, T3, free T4 and reverse T3 level. Other pituitary functions were normal apart from high FSH and LH level. TSH response to TRH stimulation was normal, but there was impaired T3 response to TRH. MRI of pituitary showed no significant changes. He continued glue sniffing after discharge. He repeatedly came to our hospital for recurrent hypokalemic paralysis. His serum T4 and free T4 level were low when he had certain amount of glue sniffing and it returned to normal after he stopped sniffing or sniffed less amount of glue. His serum T3 concentrations were normal most of the times thereafter. His FSH and LH level were persistently elevated, even after he did not sniff glue for 2 weeks. Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism. Toluene, a neurotoxic organic solvent, is present in glues. Being highly lipophilic, it can easily enter and is retained within the lipid-rich nervous system after being inhaled. Like other organic solvents, toluene has been shown to affect dopaminergic and adrenergic turnover within various parts of the brain. The effects on these neurotransmitters could lead to abnormal secretion of pituitary hormones resulting in transient central hypothyroidism and abnormal gonadotropin levels. Long-term harmful effect of central hypothyroidism and chronic influence of abnormal gonadotropins to reproduction function needs further observation.
Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation.
Mammadova-Bach, Elmina; Ollivier, Véronique; Loyau, Stéphane; Schaff, Mathieu; Dumont, Bénédicte; Favier, Rémi; Freyburger, Geneviève; Latger-Cannard, Véronique; Nieswandt, Bernhard; Gachet, Christian; Mangin, Pierre H; Jandrot-Perrus, Martine
2015-07-30
Fibrin, the coagulation end product, consolidates the platelet plug at sites of vascular injury and supports the recruitment of circulating platelets. In addition to integrin αIIbβ3, another as-yet-unidentified receptor is thought to mediate platelet interaction with fibrin. Platelet glycoprotein VI (GPVI) interacts with collagen and several other adhesive macromolecules. We evaluated the hypothesis that GPVI could be a functional platelet receptor for fibrin. Calibrated thrombin assays using platelet-rich plasma (PRP) showed that tissue factor-triggered thrombin generation was impaired in GPVI-deficient patients and reduced by the anti-GPVI Fab 9O12. Assays on reconstituted PRP and PRP from fibrinogen-deficient patients revealed a fibrinogen-dependent enhancement of thrombin generation, which relied on functional GPVI. The effect of GPVI was found to depend on fibrin polymerization. A binding assay showed a specific interaction between GPVI-Fc and fibrin, inhibited by the Fab 9O12. This Fab also reduced platelet adhesion to fibrin at low (300 s(-1)) and high (1500 s(-1)) wall shear rates. Platelets adherent to fibrin displayed shape change, exposure of procoagulant phospholipids, and the formation of small clots. When hirudinated blood was perfused at 1500 s(-1) over preformed fibrin-rich clots, the Fab 9O12 decreased the recruitment of platelets by up to 85%. This study identifies GPVI as a platelet receptor for polymerized fibrin with 2 major functions: (1) amplification of thrombin generation and (2) recruitment of circulating platelets to clots. These so-far-unrecognized properties of GPVI confer on it a key role in thrombus growth and stabilization. © 2015 by The American Society of Hematology.
Bagó, Juli R.; Pegna, Guillaume J.; Okolie, Onyi; Hingtgen, Shawn D.
2016-01-01
Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types. PMID:26803410
Cole, Heather A.; Ohba, Tetsuro; Nyman, Jeffry S.; Hirotaka, Haro; Cates, Justin M. M.; Flick, Matthew J.; Degen, Jay L.; Schoenecker, Jonathan G.
2015-01-01
Objective Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related co-morbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Methods Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αMβ2 binding motif. Results Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αMβ2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αMβ2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Conclusion Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. PMID:24664548
Alves, Christina S.; Konstantopoulos, Konstantinos
2012-01-01
Fibrin(ogen) mediates sustained tumor cell adhesion and survival in the pulmonary vasculature, thereby facilitating the metastatic dissemination of tumor cells. CD44 is the major functional fibrin receptor on colon carcinoma cells. Growth factors, such as platelet-derived growth factor (PDGF), induce post-translational protein modifications, which modulate ligand binding activity. In view of the roles of PDGF, fibrin(ogen) and CD44 in cancer metastasis, we aimed to delineate the effect of PDGF on CD44-fibrin recognition. By immunoprecipitating CD44 from PDGF-treated and untreated LS174T colon carcinoma cells, which express primarily CD44v, we demonstrate that PDGF enhances the adhesion of CD44v-coated beads to immobilized fibrin. Enzymatic inhibition studies coupled with flow-based adhesion assays and autoradiography reveal that PDGF augments the binding of CD44v to fibrin by significantly attenuating the extent of CD44 sulfation primarily on chondroitin and dermatan sulfate chains. Surface plasmon resonance assays confirm that PDGF enhances the affinity of CD44v-fibrin binding by markedly reducing its dissociation rate while modestly increasing the association rate. PDGF mildly reduces the affinity of CD44v-hyaluronan binding without affecting selectin-CD44v recognition. The latter is attributed to the fact that CD44v binds to selectins via sialofucosylated O-linked residues independent of heparan, dermatan and chondroitin sulfates. Interestingly, PDGF moderately reduces the sulfation of CD44s and CD44s-fibrin recognition. Collectively, these data offer a novel perspective into the mechanism by which PGDF regulates CD44-dependent binding of metastatic colon carcinoma cells to fibrin(ogen). PMID:23056168
Arulmoli, Janahan; Wright, Heather J.; Phan, Duc T.T.; Sheth, Urmi; Que, Richard A.; Botten, Giovanni A.; Keating, Mark; Botvinick, Elliot L.; Pathak, Medha M.; Zarembinski, Thomas I.; Yanni, Daniel S.; Razorenova, Olga V.; Hughes, Christopher C.W.; Flanagan, Lisa A.
2017-01-01
Human neural stem/progenitor cells (hNSPCs) are good candidates for treating central nervous system (CNS) trauma since they secrete beneficial trophic factors and differentiate into mature CNS cells; however, many cells die after transplantation. This cell death can be ameliorated by inclusion of a biomaterial scaffold, making identification of optimal scaffolds for hNSPCs a critical research focus. We investigated the properties of fibrin-based scaffolds and their effects on hNSPCs and found that fibrin generated from salmon fibrinogen and thrombin stimulates greater hNSPC proliferation than mammalian fibrin. Fibrin scaffolds degrade over the course of a few days in vivo, so we sought to develop a novel scaffold that would retain the beneficial properties of fibrin but degrade more slowly to provide longer support for hNSPCs. We found combination scaffolds of salmon fibrin with interpenetrating networks (IPNs) of hyaluronic acid (HA) with and without laminin polymerize more effectively than fibrin alone and generate compliant hydrogels matching the physical properties of brain tissue. Furthermore, combination scaffolds support hNSPC proliferation and differentiation while significantly attenuating the cell-mediated degradation seen with fibrin alone. HNSPCs express two fibrinogen-binding integrins, αVβ1 and α5β1, and several laminin binding integrins (α7β1, α6β1, α3β1) that can mediate interaction with the scaffold. Lastly, to test the ability of scaffolds to support vascularization, we analyzed human cord blood-derived endothelial cells alone and in co-culture with hNSPCs and found enhanced vessel formation and complexity in co-cultures within combination scaffolds. Overall, combination scaffolds of fibrin, HA, and laminin are excellent biomaterials for hNSPCs. PMID:27475528
Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S; Hirotaka, Haro; Cates, Justin M M; Flick, Matthew J; Degen, Jay L; Schoenecker, Jonathan G
2014-08-01
Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. Copyright © 2014 by the American College of Rheumatology.
Smith, A.M.; Robinson, T. M.; Salt, M. D.; Hamilton, K. S.; Silvia, B. E.; Blasiak, R.
2009-01-01
The cross-linking interactions that provide cohesive strength to molluscan adhesive gels were investigated. Metal-based interactions have been shown to play an important role in the glue of the slug Arion subfuscus (Draparnaud), but other types of interactions may also contribute to the glue's strength and their role has not been investigated. This study shows that treatments that normally disrupt hydrophobic or electrostatic interactions have little to no effect on the slug glue. High salt concentrations and non-ionic detergent do not affect the solubility of the proteins in the glue or the ability of the glue proteins to stiffen gels. In contrast, metal chelation markedly disrupts the gel. Experiments with gel filtration chromatography identify a 40 kDa protein that is a central component of the cross-links in the glue. This 40 kDa protein forms robust macromolecular aggregations that are stable even in the presence of high concentrations of salt, non-ionic detergent, urea or metal chelators. Metal chelation during glue secretion, however, may block some of these cross-links. Such robust, non-specific interactions in an aqueous environment are highly unusual for hydrogels and reflect an intriguing cross-linking mechanism. PMID:18952190
Dynamics of spider glue adhesion: effect of surface energy and contact area
NASA Astrophysics Data System (ADS)
Amarpuri, Gaurav; Chen, Yizhou; Blackledge, Todd; Dhinojwala, Ali
Spider glue is a unique biological adhesive which is humidity responsive such that the adhesion continues to increase upto 100% relative humidity (RH) for some species. This is unlike synthetic adhesives that significantly drop in adhesion with an increase in humidity. However, most of adhesion data reported in literature have used clean hydrophilic glass substrate, unlike the hydrophobic, and charged insect cuticle surface that adheres to spider glue in nature. Previously, we have reported that the spider glue viscosity changes over five orders of magnitude with humidity. Here, we vary the surface energy and surface charge of the substrate to test the change in Larnioides cornutus spider glue adhesion with humidity. We find that an increase in both surface energy and surface charge density increases the droplet spreading and there exists an optimum droplet contact area where adhesion is maximized. Moreover, spider glue droplets act as reusable adhesive for low energy hydrophobic surface at the optimum humidity. These results explain why certain prey are caught more efficiently by spiders in their habitat. The mechanism by which spider species tune its glue adhesion for local prey capture can inspire new generation smart adhesives.
Smith, A M; Robinson, T M; Salt, M D; Hamilton, K S; Silvia, B E; Blasiak, R
2009-02-01
The cross-linking interactions that provide cohesive strength to molluscan adhesive gels were investigated. Metal-based interactions have been shown to play an important role in the glue of the slug Arion subfuscus (Draparnaud), but other types of interactions may also contribute to the glue's strength and their role has not been investigated. This study shows that treatments that normally disrupt hydrophobic or electrostatic interactions have little to no effect on the slug glue. High salt concentrations and non-ionic detergent do not affect the solubility of the proteins in the glue or the ability of the glue proteins to stiffen gels. In contrast, metal chelation markedly disrupts the gel. Experiments with gel filtration chromatography identify a 40 kDa protein that is a central component of the cross-links in the glue. This 40 kDa protein forms robust macromolecular aggregations that are stable even in the presence of high concentrations of salt, non-ionic detergent, urea or metal chelators. Metal chelation during glue secretion, however, may block some of these cross-links. Such robust, non-specific interactions in an aqueous environment are highly unusual for hydrogels and reflect an intriguing cross-linking mechanism.
Molecular mechanism for adhesion in humid conditions - lessons from spider glue
NASA Astrophysics Data System (ADS)
Amarpuri, Gaurav; Singla, Saranshu; Dhopatkar, Nishad; Blackledge, Todd; Dhinojwal, Ali
Adhesion in humid conditions is a fundamental challenge for both natural and synthetic adhesives. Water lubricates the interface between the adhesive and the substrate resulting in an interfacial failure at high humidity. Yet, glue from most spider species fail cohesively at high humidity, and the spider species from wet habitat show an increase in adhesion with humidity. We use tensile testing, microscopy and surface sensitive spectroscopy techniques to probe the mechanism of spider glue adhesion under high humidity. Humidity responsive structural changes in the glue structure are observed both at the interface and in bulk. However, the humidity responsiveness is lost after washing the water soluble low molecular weight molecules (LMM) from the glue. Many natural systems display a functional response to their environment, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic LMM that respond to humidity in a unique way. We therefore anticipate that manipulation of polymer-LMM interaction can provide a simple mechanism to design humidity responsive smart adhesives. We acknowledge support from National Science Foundation Grant IOS-1257719.
NASA Astrophysics Data System (ADS)
Janzen, Kathryn Louise
Largely because of their resistance to magnetic fields, silicon photomultipliers (SiPMs) are being considered as the readout for the GlueX Barrel Calorimeter, a key component of the GlueX detector located immediately inside a 2.2 T superconducting solenoid. SiPMs with active area 1 x 1 mm2 have been investigated for use in other experiments, but detectors with larger active areas are required for the GlueX BCAL. This puts the GlueX collaboration in the unique position of being pioneers in the use of this frontend detection revolution by driving the technology for larger area sensors. SensL, a photonics research and development company in Ireland, has been collaborating with the University of Regina GlueX group to develop prototype large area SiPMs comprising 16 - 3x3 mm2 cells assembled in a close-packed matrix. Performance parameters of individual SensL 1x1 mm2 and 3x3 mm2 SiPMs along with prototype SensL SiPM arrays are tested, including current versus voltage characteristics, photon detection efficiency, and gain uniformity, in an effort to determine the suitability of these detectors to the GlueX BCAL readout.
Brown, Ashley C.; Barker, Thomas H.
2013-01-01
Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of polymerization of the material, fibrin has been widely utilized as a biomaterial for over a century. Modifying the macroscopic properties of fibrin, such as elasticity and porosity, has been somewhat elusive until recently, yet with a molecular-level rational design approach can now be somewhat easily modified through alterations of molecular interactions key to the protein’s polymerization process. This review outlines the biochemistry of fibrin and discusses methods for modification of molecular interactions and their application to fibrin based biomaterials. PMID:24056097
Glue Sniffers with Special Needs.
ERIC Educational Resources Information Center
O'Connor, Denis
1987-01-01
Glue sniffing and solvent misuse have seriously affected children and teenagers throughout the United Kingdom. This article discusses glue sniffing in terms of prevalence, association with disability, physical and psychological effects, signs and symptoms, counseling for sniffers, and successful interventions including an approach using videotape…
Plasminogen fragments K 1-3 and K 5 bind to different sites in fibrin fragment DD.
Grinenko, T V; Kapustianenko, L G; Yatsenko, T A; Yusova, O I; Rybachuk, V N
2016-01-01
Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.
Wittmann, Katharina; Storck, Katharina; Muhr, Christian; Mayer, Helena; Regn, Sybille; Staudenmaier, Rainer; Wiese, Hinrich; Maier, Gerhard; Bauer-Kreisel, Petra; Blunk, Torsten
2016-10-01
Adipose tissue engineering aims at the restoration of soft tissue defects and the correction of contour deformities. It is therefore crucial to provide functional adipose tissue implants with appropriate volume stability. Here, we investigate two different fibrin formulations, alone or in combination with biodegradable polyurethane (PU) scaffolds as additional support structures, with regard to their suitability to generate volume-stable adipose tissue constructs. Human adipose-derived stem cells (ASCs) were incorporated in a commercially available fibrin sealant as well as a stable fibrin hydrogel previously developed by our group. The composite constructs made from the commercially available fibrin and porous poly(ε-caprolactone)-based polyurethane scaffolds exhibited increased volume stability as compared to fibrin gels alone; however, only constructs using the stable fibrin gels completely maintained their size and weight for 21 days. Adipogenesis of ASCs was not impaired by the additional PU scaffold. After induction with a common hormonal cocktail, for constructs with either fibrin formulation, strong adipogenic differentiation of ASCs was observed after 21 days in vitro. Furthermore, upregulation of adipogenic marker genes was demonstrated at mRNA (PPARγ, C/EBPα, GLUT4 and aP2; qRT-PCR) and protein (leptin; ELISA) levels. Stable fibrin/PU constructs were further evaluated in a pilot in vivo study, resulting in areas of well-vascularized adipose tissue within the implants after only 5 weeks. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.
Niwa, Kazuki; Mimuro, Jun; Miyata, Masaaki; Sugo, Teruko; Ohmori, Tsukasa; Madoiwa, Seiji; Tei, Chuwa; Sakata, Yoichi
2008-01-01
Emerging lines of evidence have suggested that certain dysfibrinogens present a significant risk of thrombosis. The thrombophilic nature of a new-type of dysfibrinogen Kagoshima identified in a 36-year-old female with deep vein thrombosis during the postpartum period was studied. Based on the analyses of the patient fibrinogen and the fibrinogen genes, fibrinogen Kagoshima was shown to have the amino acid substitution of gammaThr-314 to Ile that resulted in impaired function and hypofibrinogenemia. Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium ions, causing very low clottability and delayed cross-linking of patient fibrin catalyzed by activated factor XIII. Because of the low clottability, a large amount of soluble fibrin was formed upon thrombin treatment, resulting in an increase of thrombin in the soluble fraction. Additionally, tPA-mediated plasmin generation on fibrin was impaired and calcium-ion-dependent integrity of the gamma-chain D domain of Kagoshima fibrinogen was perturbed. The presence of many tapered-fiber ends inside the tangled fibrin networks, observed by scanning electron microscopy, suggested early termination of fibrin polymerization and the structural alteration. These data suggest that fibrinogen Kagoshima is dysfunctional, giving rise to formation of fibrinolysis-resistant soluble fibrin polymers and entrance of soluble fibrin associating with thrombin to the circulation, partly accounting for the thrombophilic nature of the affected fibrinogen and fibrin molecules.
Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei
2013-01-01
Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIb)β₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.
Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei
2013-01-01
Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an αIIbβ3 antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment. PMID:23383331
Lytic resistance of fibrin containing red blood cells
Wohner, Nikolett; Sótonyi, Péter; Machovich, Raymund; Szabó, László; Tenekedjiev, Kiril; Silva, Marta M.C.G.; Longstaff, Colin; Kolev, Krasimir
2012-01-01
Objective Arterial thrombi contain variable amounts of red blood cell (RBC), which interact with fibrinogen through an eptifibatide-sensitive receptor and modify the structure of fibrin. Here we evaluate the modulator role of RBCs in the lytic susceptibility of fibrin. Methods and Results If fibrin is formed at increasing RBC counts, scanning electron microscopy evidenced a decrease in fiber diameter from 150 nm to 96 nm at 40 %(v/v) RBC, an effect susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBC prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue plasminogen activator (tPA) by up to 22.7±1.6 %, but not in the presence of eptifibatide. Confocal laser microscopy using green fluorescent protein (GFP)-labeled tPA and orange fluorescent fibrin showed that 20-40 %(v/v) RBC significantly slowed down the dissolution of the clots. tPA-GFP did not accumulate on the surface of fibrin containing RBC at any cell count above 10 %. The presence of RBC in the clot suppressed the tPA-induced plasminogen activation resulting in a 45 % less plasmin generated after 30 min activation at 40 %(v/v) RBC. Conclusion RBCs confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC interactions. PMID:21737785
Silva, Raúl F; Carmona, Jorge U; Rezende, Cleuza M F
2013-04-15
The aim of this study was to use transmission electron microscopy to describe the ultrastructural characteristics of clots obtained from canine and feline platelet concentrates (PC) that had been activated with calcium gluconate (CG) or CG plus batroxobin (CGB). Platelets from fibrin clots were classified according their morphological changes. The area of the intercellular space (μm2), the area of the fibrin fibers (μm2), and the width of the fibrin fibers (μm) were determined for the dog clots. The platelet area (μm2), the area of fibrin fibers (μm2), the ratio of the minor and major axes of platelets, the ratio of the major and minor axes of platelets, and the number of α-granules found within platelets were measured for the cat clots. Cat platelets displayed full activation. Dog platelets displayed lysis with loss of normal architecture. In both species, a statistically significant difference was found (P < 0.01) between the fibrin fiber measurements in the PC clots activated with CG and CGB. The findings suggest that activation with CG caused platelet alpha granules to release their contents. In cats, fibrin production was greater when the PC was activated with CG. In dogs, activation with CG produced thick fibrin fibers.
Ma, Kun; Titan, Ashley L.; Stafford, Melissa; Zheng, Chun hua; Levenston, Marc E.
2012-01-01
Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with distinct advantages and disadvantages to each material. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg/mL fibrinogen blended with 8 mg/mL alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition. PMID:22750738
Cell culture in autologous fibrin scaffolds for applications in tissue engineering.
de la Puente, Pilar; Ludeña, Dolores
2014-03-10
In tissue engineering techniques, three-dimensional scaffolds are needed to adjust and guide cell growth and to allow tissue regeneration. The scaffold must be biocompatible, biodegradable and must benefit the interactions between cells and biomaterial. Some natural biomaterials such as fibrin provide a structure similar to the native extracellular matrix containing the cells. Fibrin was first used as a sealant based on pools of commercial fibrinogen. However, the high risk of viral transmission of these pools led to the development of techniques of viral inactivation and elimination and the use of autologous fibrins. In recent decades, fibrin has been used as a release system and three-dimensional scaffold for cell culture. Fibrin scaffolds have been widely used for the culture of different types of cells, and have found several applications in tissue engineering. The structure and development of scaffolds is a key point for cell culture because scaffolds of autologous fibrin offer an important alternative due to their low fibrinogen concentrations, which are more suitable for cell growth. With this review our aim is to follow methods of development, analyze the commercial and autologous fibrins available and assess the possible applications of cell culture in tissue engineering in these three-dimensional structures. Copyright © 2013 Elsevier Inc. All rights reserved.
Math, Souvik; Horn, Roger; Jayaram, Vikram; Biswas, Sanjay Kumar
2007-04-15
Currently data obtained from surface force apparatus experiments are convoluted with the mechanical response of glue of unknown thickness, used to bond mica sheets to the substrates. This paper describes a formulation to precisely deconvolute out the forces between the mica sheets by determining the thickness of glue, knowing the mechanical properties of the glue. The formulation consists of a general solution based on the noniterative Hankel transform of the Laplace equation. The generality is achieved by treating all the layers except the one in contact as an effective lumped system consisting of a set of springs in series, where each spring represents a layer. The solution is validated by nanoindentation of trilayer systems consisting of layers with widely diverse mechanical properties, some differing from each other by three orders of magnitude. SFA experiments are done with carefully metered slabs of glue. The proposed method is validated by comparing the actual glue thicknesses with those determined using the present analysis.
Use of cyanoacrylate glue for temporary tarsorrhaphy in children.
Trivedi, Dipti; McCalla, Maureen; Squires, Zoe; Parulekar, Manoj
2014-01-01
Congenital anophthalmia and postenucleation socket contracture are difficult conditions that require serial socket expansion with the use of hydrogel expanders and custom-made conformers along with temporary tarsorrhaphy. The authors undertook a part prospective case review of all children undergoing temporary tarsorrhaphy using cyanoacrylate glue over a 3-year period at a tertiary specialist children's hospital. They report a series of 7 children undergoing temporary tarsorrhaphy with cyanoacrylate glue instead of the conventional suturing technique. Indications were socket expansion (n = 4), fornix deepening (n = 2), prosthesis reposition, and prolapsed conjunctiva following enucleation (n = 1).The age range was 3 weeks to 14 years (mean, 2.7 years). The glue tarsorrhaphy lasted between 0.5 and 13 weeks (mean, 4.5 weeks). There were no adverse outcomes, and the glue tarsorrhaphy was tolerated well in all cases, with relative ease of reapplication of glue in clinic. Their study demonstrates that this technique allows quick and efficient temporary tarsorrhaphy with relative ease of reapplication in a clinic setting, avoiding the need for multiple general anesthetics.
ELECTROMAGNETICALLY INDUCED DISTORTION OF A FIBRIN MATRIX WITH EMBEDDED MICROPARTICLES
SCOGIN, TYLER; YESUDASAN, SUMITH; WALKER, MITCHELL L. R.
2018-01-01
Blood clots occur in the human body when they are required to prevent bleeding. In pathological states such as diabetes and sickle cell disease, blood clots can also form undesirably due to hypercoagulable plasma conditions. With the continued effort in developing fibrin therapies for potential life-saving solutions, more mechanical modeling is needed to understand the properties of fibrin structures with inclusions. In this study, a fibrin matrix embedded with magnetic micro particles (MMPs) was subjected to a magnetic field to determine the magnitude of the required force to create plastic deformation within the fibrin clot. Using finite element (FE) analysis, we estimated the magnetic force from an electromagnet at a sample space located approximately 3 cm away from the coil center. This electromagnetic force coupled with gravity was applied on a fibrin mechanical system with MMPs to calculate the stresses and displacements. Using appropriate coil parameters, it was determined that application of a magnetic field of 730 A/m on the fibrin surface was necessary to achieve an electromagnetic force of 36 nN (to engender plastic deformation). PMID:29628543
Fibrin matrices: The versatile therapeutic delivery systems.
Ahmad, Ejaj; Fatima, Munazza Tamkeen; Hoque, Mehboob; Owais, Mohammad; Saleemuddin, Mohammed
2015-11-01
Fibrin sealants, that have been employed for over a century by surgeons to stop post surgery bleeding, are finding novel applications in the controlled delivery of antibiotics and several other therapeutics. Fibrinogen can be easily purified from blood plasma and converted by thrombolysis to fibrin that undergoes spontaneous aggregation to form insoluble clot. During the gelling, fibrin can be formulated into films, clots, threads, microbeads, nanoconstructs and nanoparticles. Whole plasma clots in the form of beads and microparticles can also be prepared by activating endogenous thrombin, for possible drug delivery. Fibrin formulations offer remarkable scope for controlling the porosity as well as in vivo degradability and hence the release of the associated therapeutics. Binding/covalent-linking of therapeutics to the fibrin matrix, crosslinking of the matrix with bifunctional reagents and coentrapment of protease inhibitors have been successful in regulating both in vitro and in vivo release of the therapeutics. The release rates can also be remarkably lowered by preentrapment of therapeutics in insoluble particles like liposomes or by anchoring them to the matrix via molecules that bind them as well as fibrin. Copyright © 2015 Elsevier B.V. All rights reserved.
Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.
Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R
2013-06-18
Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Fibrin Sealants in Dura Sealing: A Systematic Literature Review
2016-01-01
Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993
Fibrin Sealants in Dura Sealing: A Systematic Literature Review.
Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo
2016-01-01
Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.
Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion
NASA Astrophysics Data System (ADS)
Chernysh, Irina N.; Nagaswami, Chandrasekaran; Purohit, Prashant K.; Weisel, John W.
2012-11-01
Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that in vivo clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization, and suggest a target for therapeutic intervention.
Eshghpour, Majid; Majidi, Mohamad Reza; Nejat, Amir Hossein
2012-01-01
Introduction: The healing process after surgery is a challenging issue for surgeons. Various materials and techniques have been developed to facilitate this process and reduce its period. Fibrin adhesives are often used in cardiothoracic and vascular surgery to seal diffuse microvascular bleeding and in general and plastic surgery to seal wound borders. This Case report and literature review will introduce the various usages of platelet-rich fibrin in different surgical procedures and the method of producing the matrix. Case Report: A 24-year old man with periorbital skin avulsion treated with PRF membrane has been reported and discussed in this paper. Conclusion: Platelet-rich fibrin is a natural autologous fibrin matrix, which can be produced with a simple blood sample and a table centrifuge. The material has been used in a wide range of surgical procedures to shorten the healing period and reduce post-surgical complications. PMID:24303410
Fibrin adhesive is better than sutures in pterygium surgery.
Ratnalingam, Vanitha; Eu, Andrew Lim Keat; Ng, Gim Leong; Taharin, Rohana; John, Elizabeth
2010-05-01
To evaluate the recurrence rate, surgical time, and postoperative pain between conjunctival autografting with sutures and with fibrin adhesive in pterygium surgery. A prospective, randomized, double-blind, clinical trial on the benefits of using fibrin adhesive in place of sutures in pterygium surgery. One hundred seventy-five eyes with primary pterygium were randomized to undergo pterygium surgery with conjunctival autograft transplantation using either fibrin adhesive or sutures. One hundred thirty-seven eyes of 113 patients that were operated on by a single surgeon (V.R.) completed the 1-year follow-up. Sixty-eight eyes were operated with fibrin adhesive and 69 eyes with sutures. Patients were followed up at 1 day, 1 week, 1 month, 6 months, and 1 year after surgery. Pterygium recurrence and postoperative pain was graded by an independent observer (A.L.) masked to the method of treatment. Surgical time was measured with a stopwatch. All patients were followed up for 1 year. There were 3 recurrences (4.41%) in the fibrin adhesive group and 11 recurrences (15.9%) in the suture group. The mean duration required to complete surgery in the fibrin adhesive group was 16.93 +/- 2.85 minutes, whereas that of the suture group was 29.84 +/- 5.65 minutes, which was statistically significant (P < 0.001). The immediate postoperative pain score and week 1 postoperative pain score were significantly lower in the fibrin adhesive group (P < 0.05). No major complications were observed in either group. The use of fibrin adhesive in primary pterygium surgery with conjunctival autografts reduces the recurrence rate, surgical time, and postoperative pain when compared with sutures.
Krazy Glue® in the ear: A case report of child abuse.
Sorichetti, Brendan D; Fandiño, Marcela; Kozak, Frederick K
2018-06-01
Krazy Glue ® or cyanoacrylate glue is an acrylic resin that polymerizes in less than a minute when in contact with moisture or water. We present a case of a one month old referred to our tertiary pediatric otolaryngology clinic from an outside emergency department with a history of application of cyanoacrylate glue in the external ear canals. This report presents the management of this case along with the medical and legal outcomes surrounding this case of child abuse. Copyright © 2018. Published by Elsevier B.V.
Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Soleimani, Masoud; Nadri, Samad; Tavangar, Seyed Mohammad; Roohipoor, Ramak; Yazdankhah, Meysam; Bayat, Neda; Riazi-Esfahani, Mohammad; Ai, Jafar
2018-06-01
Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue. In this study fibrin gel was used as hydrogel scaffold for immobilization of cells. The structural characteristics of fibrin gel scaffold were examined with SEM. Rheological properties of fibrin gel were measured by rheometer and biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem cells CJMSCs, the cells were differentiated into photoreceptor-like cells by exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as photoreceptor-like cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM analysis showed CJMSCs were well attached in fibrin gels and there were good integrity between cells and scaffold. The elastic modulus and constant degradation of the gel contributes to the growth and proliferation of cells. There was no toxicity effect of fibrin hydrogel on cells and the viability of cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After 2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and RPE65 as special markers of photoreceptor cells were detected by Real time PCR and immunofluorescence that these expressions in 3 D groups were higher than TCP groups. In conclusion, our findings showed that application of readily available sources of adult stem cells like human conjunctiva stem cells encapsulated in fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell numbers for repair and regeneration of retina disease such as photoreceptor injury.
Zhao, Wenxue; Han, Qianqian; Lin, Hang; Gao, Yuan; Sun, Wenjie; Zhao, Yannan; Wang, Bin; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu
2008-10-01
Targeted therapy is a new generation of therapeutics, where two critical factors are involved. One is the particular molecular target, and the other is the specific target-binding drug. In this work, the fibrin, a main component of plasma clot at wound sites, was used as the target for human bFGF, aiming to improve therapeutic neovascularization and wound repair. To endow bFGF with fibrin-targeting ability, a fibrin-binding peptide Kringle1 (K1), derived from human plasminogen, was fused to human bFGF. The recombinant K1bFGF showed high fibrin and plasma-clot-binding ability. When applied to the wound sites with plasma clots, K1bFGF induced robust neovascularization and improved wound healing. To extend the application of K1bFGF to other cases where no plasma clots exist, we developed a fibrin-scaffold/K1bFGF system. This system could induce localized neovascularization by delivery of K1bFGF in a sustained and site-targeting manner, and provide a microenvironment promoting cell growth and tissue regeneration. In summary, we successfully used the pathologic environment fibrin clot as the target for bFGF, and based on which bFGF was designed into a targeting agent by introduction of a fibrin-binding peptide. This provides a potential approach to improve therapeutic neovascularization and wound repair.
Reconstruction of living bilayer human skin equivalent utilizing human fibrin as a scaffold.
Mazlyzam, A L; Aminuddin, B S; Fuzina, N H; Norhayati, M M; Fauziah, O; Isa, M R; Saim, L; Ruszymah, B H I
2007-05-01
Our aim of this study was to develop a new methodology for constructing a bilayer human skin equivalent to create a more clinical compliance skin graft composite for the treatment of various skin defects. We utilized human plasma derived fibrin as the scaffold for the development of a living bilayer human skin equivalent: fibrin-fibroblast and fibrin-keratinocyte (B-FF/FK SE). Skin cells from six consented patients were culture-expanded to passage 1. For B-FF/FK SE formation, human fibroblasts were embedded in human fibrin matrix and subsequently another layer of human keratinocytes in human fibrin matrix was stacked on top. The B-FF/FK SE was then transplanted to athymic mice model for 4 weeks to evaluate its regeneration and clinical performance. The in vivo B-FF/FK SE has similar properties as native human skin by histological analysis and expression of basal Keratin 14 gene in the epidermal layer and Collagen type I gene in the dermal layer. Electron microscopy analysis of in vivo B-FF/FK SE showed well-formed and continuous epidermal-dermal junction. We have successfully developed a technique to engineer living bilayer human skin equivalent using human fibrin matrix. The utilization of culture-expanded human skin cells and fibrin matrix from human blood will allow a fully autologous human skin equivalent construction.
Chiti, Maria Costanza; Dolmans, Marie-Madeleine; Mortiaux, Lucie; Zhuge, Flanco; Ouni, Emna; Shahri, Parinaz Asiabi Kohneh; Van Ruymbeke, Evelyne; Champagne, Sophie-Demoustier; Donnez, Jacques; Amorim, Christiani Andrade
2018-01-01
The aim of this study is to optimize fibrin matrix composition in order to mimic human ovarian tissue architecture for human ovarian follicle encapsulation and grafting. Ultrastructure of fresh human ovarian cortex in age-related women (n = 3) and different fibrin formulations (F12.5/T1, F30/T50, F50/T50, F75/T75), rheology of fibrin matrices and histology of isolated and encapsulated human ovarian follicles in these matrices. Fresh human ovarian cortex showed a highly fibrous and structurally inhomogeneous architecture in three age-related patients, but the mean ± SD of fiber thickness (61.3 to 72.4 nm) was comparable between patients. When the fiber thickness of four different fibrin formulations was compared with human ovarian cortex, F50/T50 and F75/T75 showed similar fiber diameters to native tissue, while F12.5/T1 was significantly different (p value < 0.01). In addition, increased concentrations of fibrin exhibited enhanced storage modulus with F50/T50, resembling physiological ovarian rigidity. Excluding F12.5/T1 from further analysis, only three remaining fibrin matrices (F30/T50, F50/T50, F75/T75) were histologically investigated. For this, frozen-thawed fragments of human ovarian tissue collected from 22 patients were used to isolate ovarian follicles and encapsulate them in the three fibrin formulations. All three yielded similar follicle recovery and loss rates soon after encapsulation. Therefore, based on fiber thickness, porosity, and rigidity, we selected F50/T50 as the fibrin formulation that best mimics native tissue. Of all the different fibrin matrix concentrations tested, F50/T50 emerged as the combination of choice in terms of ultrastructure and rigidity, most closely resembling human ovarian cortex.
Batman, C; Ozdamar, Y; Mutevelli, S; Sonmez, K; Zilelioglu, G; Karakaya, J
2009-06-01
To describe the use of tissue glue to close scleral and conjunctival wounds, and to compare the clinical outcomes using tissue glue and vicryl suture for closing these areas in conventional 20-gauge (G) vitrectomy. Thirty eyes of 30 patients were included in this study. The indications for vitreoretinal surgery were diabetic vitreous haemorrhage with severe vitreoretinal traction in 10 eyes, retinal detachment and proliferative vitreoretinopathy in 14 eyes, and vitreous opacity in 6 eyes. Tissue glue (Tisseel, Baxter AG Industries, Vienna, Austria) was used to attach scleral and conjunctival wounds in 15 eyes and vicryl sutures in 15 eyes. The patients were allotted into two subgroups as tissue glue group (TG) and vicryl suture group (VG). The sclerotomy sites were evaluated with ultrasound biomicroscopy (UBM) postoperatively in TG. Follow-up period was 2 months. The groups were statistically compared for ocular signs and symptoms by Mann-Whitney U-test. No scleral wound leakage and conjunctival reattachment were observed at the end of the surgical procedure and during the follow-up period. No adverse effects were seen in TG. Abnormal fibrous ingrowth was not detected at the sclerotomy sites by means of UBM in TG. Patient comfort was significantly higher in TG than VG (P<0.05). Tissue glue has no adverse effects on ocular tissue and can be used as a substitute for suture materials, and the use of tissue glue decreases patient symptoms during the postoperative period after 20-G vitrectomy. Tissue glue can enable to perform sutureless surgery in the conventional 20-G vitrectomy.
Identification of quantitative trait loci for fibrin clot phenotypes: The EuroCLOT study
Williams, Frances MK; Carter, Angela M; Kato, Bernet; Falchi, Mario; Bathum, Lise; Surdulescu, Gabriela; Kyvik, Kirsten Ohm; Palotie, Aarno; Spector, Tim D; Grant, Peter J
2012-01-01
Objectives Fibrin makes up the structural basis of an occlusive arterial thrombus and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to 1) determine the heritability of fibrin phenotypes and 2) identify QTLs associated with fibrin phenotypes. Methods 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK Caucasian female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Results Estimates of heritability for d-dimer and turbidometric variables were in the range 17 - 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD>3 on 5 chromosomes (5, 6, 9, 16 and 17). Conclusions The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischaemic cardiovascular disorders and their therapy. PMID:19150881
Commissioning of the pair spectrometer of the GlueX experiment
Somov, A.; Tolstukhin, I.; Somov, S. V.; ...
2017-03-07
The main goal of the pair spectrometer of the GlueX experiment at Jefferson Lab is to determine the photon beam flux and to measure beam polarization. Here, we present the design of the pair spectrometer and the performance results during the first commissioning runs of the GlueX experiment.
Bhatia, Vikram
2012-01-01
A large part of portal venous system and the paragastric and para-esophageal collateral circulation is within the reach of endoscopic ultrasound (EUS). The EUS is more sensitive than gastroscopy for the detection of gastric varices (GV), and can accurately distinguish GV from thickened gastric folds. Gastric varices are depicted by serpiginous, anechoic, Doppler-positive mural channels, with larger collateral channels visible outside the gastric wall. The EUS has also been used to monitor the completeness of GV obturation after glue injection. There are limited data that this strategy may be clinically beneficial to prevent GV re-bleed. The EUS has been used to deliver glue injections under real-time monitoring into the vascular channels, with or without steel coils as scaffolding for the glue. The potential advantages of this technique include a straight scope position, lack of hindrance from pooled blood in gastric fundus, smaller glue volume requirements, and precise intra-vascular placement of glue with avoidance of intramural injections, and reduced embolic complications. PMID:25755407
Glue detection based on teaching points constraint and tracking model of pixel convolution
NASA Astrophysics Data System (ADS)
Geng, Lei; Ma, Xiao; Xiao, Zhitao; Wang, Wen
2018-01-01
On-line glue detection based on machine version is significant for rust protection and strengthening in car production. Shadow stripes caused by reflect light and unevenness of inside front cover of car reduce the accuracy of glue detection. In this paper, we propose an effective algorithm to distinguish the edges of the glue and shadow stripes. Teaching points are utilized to calculate slope between the two adjacent points. Then a tracking model based on pixel convolution along motion direction is designed to segment several local rectangular regions using distance. The distance is the height of rectangular region. The pixel convolution along the motion direction is proposed to extract edges of gules in local rectangular region. A dataset with different illumination and complexity shape stripes are used to evaluate proposed method, which include 500 thousand images captured from the camera of glue gun machine. Experimental results demonstrate that the proposed method can detect the edges of glue accurately. The shadow stripes are distinguished and removed effectively. Our method achieves the 99.9% accuracies for the image dataset.
SPECT imaging of fibrin using fibrin-binding peptides.
Starmans, Lucas W E; van Duijnhoven, Sander M J; Rossin, Raffaella; Aime, Silvio; Daemen, Mat J A P; Nicolay, Klaas; Grüll, Holger
2013-01-01
Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision-making on possible therapeutic options in atherosclerosis, cancer and thrombus-related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel (111)In-labeled fibrin-binding peptide (FibPep) to visualize thrombi in mice noninvasively using single-photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin-binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (K(d)) of 0.8 μ m, whereas NCFibPep displayed at least a 100-fold lower affinity towards fibrin. A FeCl3 -injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus-containing carotid in comparison to the noninjured carotid (5.7 ± 0.7 and 0.6 ± 0.4% injected dose per gram (%ID g(-1)), respectively; p < 0.01; n = 4), whereas nonspecific NCFibPep did not (0.4 ± 0.2 and 0.3 ± 0.0%ID g(-1), respectively; n = 4). In conclusion, FibPep displayed high affinity towards fibrin in vitro and rapid blood clearance in vivo, and allowed sensitive detection of thrombi using SPECT imaging. Therefore, this particular imaging approach may provide a new tool to diagnose and monitor diseases such as atherosclerosis and cancer. Copyright © 2013 John Wiley & Sons, Ltd.
Abaeva, Anastasia A.; Canault, Matthias; Kotova, Yana N.; Obydennyy, Sergey I.; Yakimenko, Alena O.; Podoplelova, Nadezhda A.; Kolyadko, Vladimir N.; Chambost, Herve; Mazurov, Aleksei V.; Ataullakhanov, Fazoil I.; Nurden, Alan T.; Alessi, Marie-Christine; Panteleev, Mikhail A.
2013-01-01
Strongly activated “coated” platelets are characterized by increased phosphatidylserine (PS) surface expression, α-granule protein retention, and lack of active integrin αIIbβ3. To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the α-granule protein “coat.” Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as “cap,” a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin(ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin(ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and αIIbβ3. These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather “capped”) platelets to become incorporated into thrombi despite their lack of active integrins. PMID:23995838
Identification and characterization of α1 -antitrypsin in fibrin clots.
Talens, S; Malfliet, J J M C; van Hal, P Th W; Leebeek, F W G; Rijken, D C
2013-07-01
Preliminary studies indicated that α1 -antitrypsin (A1AT) is the most abundant protein that is non-covalently bound to fibrin clots prepared from plasma. The aim of this study was to identify and characterize fibrin(ogen)-bound A1AT. Plasma clots were prepared and extensively washed with saline. Clot-bound A1AT could only be extracted using denaturing agents such as urea, thiourea or SDS, pointing to an apparently strong association. Purified fibrinogen, but still containing A1AT as a contaminant, was gel filtered, which showed that the A1AT was bound to fibrinogen. A specific ELISA detected the presence of A1AT-fibrinogen complexes in both purified fibrinogen and pooled normal plasma. Finally, fibrin(ogen)-Sepharose chromatography indicated that A1AT purified from plasma contained a small fraction of fibrin(ogen)-binding A1AT. To study the inhibitory activity of fibrin(ogen)-bound A1AT, both fibrinogen containing A1AT and washed plasma clots were incubated with increasing amounts of elastase. SDS-PAGE and Western blotting showed under both conditions the generation of the A1AT-elastase complex as well as cleaved A1AT. The inhibitory activity of fibrin(ogen)-bound A1AT was also demonstrated by measuring elastase-induced lysis of fibrin clots. Fibrin clots contain strongly bound A1AT, which is functionally active as a serine protease inhibitor (serpin). This A1AT might play a role in the local regulation of proteases involved in coagulation or fibrinolysis and represent a novel link between the inflammatory and hemostatic systems. © 2013 International Society on Thrombosis and Haemostasis.
Brown, Ashley C.; Baker, Stephen; Douglas, Alison; Keating, Mark; Alvarez-Elizondo, Martha; Botvinick, Elliot; Guthold, Martin; Barker, Thomas H.
2015-01-01
Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular ‘interference’ of fibrin’s native polymerization mechanism. We have previously reported that engagement of fibrin’s polymerization ‘hole b’, also known as ‘b-pockets’, through PEGylated complimentary ‘knob B’ mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B-fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, Kd, increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its Kd but increases extensibility of fibers at concentrations above its Kd. The data suggest this bimodal behavior is due to the individual contributions knob B, which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics. PMID:25725552
de Barros, Caio Nunes; Miluzzi Yamada, Ana Lúcia; Junior, Rui Seabra F; Barraviera, Benedito; Hussni, Carlos Alberto; de Souza, Jaqueline Brandão; Watanabe, Marcos Jun; Rodrigues, Celso Antônio
2015-01-01
Autologous fibrin gel is commonly used as a scaffold for filling defects in articular cartilage. This biomaterial can also be used as a sealant to control small hemorrhages and is especially helpful in situations where tissue reparation capacity is limited. In particular, fibrin can act as a scaffold for various cell types because it can accommodate cell migration, differentiation, and proliferation. Despite knowledge of the advantages of this biomaterial and mastery of the techniques required for its application, the durability of several types of sealant at the site of injury remains questionable. Due to the importance of such data for evaluating the quality and efficiency of fibrin gel formulations on its use as a scaffold, this study sought to analyze the heterologous fibrin sealant developed from the venom of Crotalus durissus terrificus using studies in ovine experimental models. The fibrin gel developed from the venom of this snake was shown to act as a safe, stable, and durable scaffold for up to seven days, without causing adverse side effects. Fibrin gel produced from the venom of the Crotalus durissus terrificus snake possesses many clinical and surgical uses. It presents the potential to be used as a biomaterial to help repair skin lesions or control bleeding, and it may also be used as a scaffold when applied together with various cell types. The intralesional use of the fibrin gel from the venom of this snake may improve surgical and clinical treatments in addition to being inexpensive and adequately consistent, durable, and stable. The new heterologous fibrin sealant is a scaffold candidate to cartilage repair in this study. PMID:26264444
Regulation of Plasminogen Activation on Cell Surfaces and Fibrin.
Urano, Tetsumei; Castellino, Francis J; Suzuki, Yuko
2018-05-20
The fibrinolytic system dissolves fibrin and maintains vascular patency. Recent advances in imaging analyses allowed visualization of the spatiotemporal regulatory mechanism of fibrinolysis, as well as its regulation by other plasma haemostasis cofactors. Vascular endothelial cells (VECs) retain tissue-type plasminogen activator (tPA) after secretion and maintain high plasminogen (plg) activation potential on their surfaces. As in plasma, the serpin, plasminogen activator inhibitor type 1 (PAI-1), regulates fibrinolytic potential via inhibition of the VEC surface-bound plg activator, tPA. Once fibrin is formed, plg activation by tPA is initiated and effectively amplified on the surface of fibrin, and fibrin is rapidly degraded. The specific binding of plg and tPA to lytic edges of partly degraded fibrin via newly generated C-terminal lysine residues, which amplifies fibrin digestion, is a central aspect of this pathophysiological mechanism. Thrombomodulin (TM) plays a role in the attenuation of the plg binding on fibrin and the associated fibrinolysis, which is reversed by a carboxypeptidase B inhibitor. This suggests that the plasma procarboxypeptidase B, thrombin activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin bound to TM on VECs, is a critical aspect of the regulation of plg activation on VECs and subsequent fibrinolysis. Platelets also contain PAI-1, TAFI, TM and the fibrin crosslinking enzyme, Factor (F) XIIIa, and either secrete or expose these agents upon activation in order to regulate fibrinolysis. In this review, the native machinery of plg activation and fibrinolysis, as well as their spatiotemporal regulatory mechanisms, as revealed by imaging analyses, are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Spatiotemporal Characterization of a Fibrin Clot Using Quantitative Phase Imaging
Gannavarpu, Rajshekhar; Bhaduri, Basanta; Tangella, Krishnarao; Popescu, Gabriel
2014-01-01
Studying the dynamics of fibrin clot formation and its morphology is an important problem in biology and has significant impact for several scientific and clinical applications. We present a label-free technique based on quantitative phase imaging to address this problem. Using quantitative phase information, we characterized fibrin polymerization in real-time and present a mathematical model describing the transition from liquid to gel state. By exploiting the inherent optical sectioning capability of our instrument, we measured the three-dimensional structure of the fibrin clot. From this data, we evaluated the fractal nature of the fibrin network and extracted the fractal dimension. Our non-invasive and speckle-free approach analyzes the clotting process without the need for external contrast agents. PMID:25386701
Park, Jee Ho; Oh, Jin Young; Han, Sun Woong; Lee, Tae Il; Baik, Hong Koo
2015-03-04
A solution-processed boron-doped peroxo-zirconium oxide (ZrO2:B) thin film has been found to have multifunctional characteristics, providing both hydrophobic surface modification and a chemical glue layer. Specifically, a ZrO2:B thin film deposited on a hydrophobic layer becomes superhydrophilic following ultraviolet-ozone (UVO) treatment, whereas the same treatment has no effect on the hydrophobicity of the hydrophobic layer alone. Investigation of the ZrO2:B/hydrophobic interface layer using angle-resolved X-ray photoelectron spectroscopy (AR XPS) confirmed it to be chemically bonded like glue. Using the multifunctional nature of the ZrO2:B thin film, flexible amorphous indium oxide (In2O3) thin-film transistors (TFTs) were subsequently fabricated on a polyimide substrate along with a ZrO2:B/poly-4-vinylphenol (PVP) dielectric. An aqueous In2O3 solution was successfully coated onto the ZrO2:B/PVP dielectric, and the surface and chemical properties of the PVP and ZrO2:B thin films were analyzed by contact angle measurement, atomic force microscopy (AFM), Fourier transform infrared (FT-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The surface-engineered PVP dielectric was found to have a lower leakage current density (Jleak) of 4.38 × 10(-8) A/cm(2) at 1 MV/cm, with no breakdown behavior observed up to a bending radius of 5 mm. In contrast, the electrical characteristics of the flexible amorphous In2O3 TFT such as on/off current ratio (Ion/off) and electron mobility remained similar up to 10 mm of bending without degradation, with the device being nonactivated at a bending radius of 5 mm. These results suggest that ZrO2:B thin films could be used for low-temperature, solution-processed surface-modified flexible devices.
A Water-Borne Adhesive Modeled after the Sandcastle Glue of P. californicaa
Shao, Hui; Bachus, Kent N.
2010-01-01
Polyacrylate glue protein analogs of the glue secreted by Phragmatopoma californica, a marine polycheate, were synthesized with phosphate, primary amine, and catechol sidechains with molar ratios similar to the natural glue proteins. Aqueous mixtures of the mimetic polyelectrolytes condensed into liquid complex coacervates around neutral pH. Wet cortical bone specimens bonded with the coacervates, oxidatively crosslinked through catechol sidechains, had bond strengths nearly 40% of the strength of a commercial cyanoacrylate. The unique material properties of complex coacervates may be ideal for development of clinically useful adhesives and other biomaterials. PMID:19040222
A Synthetic Fibrin-Crosslinking Polymer for Modulating Clot Properties and Inducing Hemostasis
Chan, Leslie W.-G.; Wang, Xu; Wei, Hua; Pozzo, Lilo D.; White, Nathan J.; Pun, Suzie H.
2015-01-01
Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications. PMID:25739763
The relationship to age and cerebral vascular accidents of fibrin and fibrinolytic activity
Hume, R.
1961-01-01
Three `normal' groups of people—young, middle-aged, and old—have been investigated with regard to the fibrin content and fibrinolytic activity of the blood. The fourth group consisted of middle-aged people who had previously sustained a cerebral vascular accident matched statistically for age with the middle-aged normals. It was concluded that fibrin increases with age but there is an interaction between age and sex, the female having a higher level in the young group and the male a higher level in the middle-aged group. There was no sex difference in the levels of fibrin in the old age group. Fibrinolytic activity increases with age and there is a positive correlation between fibrin and fibrinolytic activity but no age-sex interaction. Those with cerebral vascular accidents tended to have higher fibrin levels and lower fibrinolytic activity but the differences were not statistically significant. There did, however, appear to be an increase in antifibrinolytic activity in the cerebral vascular group. PMID:13716799
Occupational contact dermatitis caused by aniline epoxy resins in the aircraft industry.
Pesonen, Maria; Suuronen, Katri; Jolanki, Riitta; Aalto-Korte, Kristiina; Kuuliala, Outi; Henriks-Eckerman, Maj-Len; Valtanen, Ilona; Alanko, Kristiina
2015-08-01
Tetraglycidyl-4,4'-methylenedianiline (TGMDA) is an aniline epoxy resin used in, for example, resin systems of pre-impregnated composite materials (prepregs) of the aircraft industry. Allergic contact dermatitis caused by TGMDA in prepregs has been described previously. To report on 9 patients with occupational allergic contact dermatitis caused by TGMDA in epoxy glues used in helicopter assembly. The patients were examined with patch testing at the Finnish Institute of Occupational Health in 2004-2009. The first patient was diagnosed by testing both components of two epoxy glues from the workplace, and was also tested with glue ingredients, including TGMDA. The following patients were tested with the glues and TGMDA. The resin parts of the glues were analysed for their epoxy compounds, including TGMDA. All of the patients had a patch test reaction to one or both of the resin parts of the TGMDA-containing glues. Eight of them had a strong allergic reaction to TGMDA, and one had a doubtful reaction to TGMDA. Two of the patients also had an allergic reaction to triglycidyl-p-aminophenol (TGPAP), another aniline epoxy resin, which was not present in the TGMDA-containing glues. In aircraft industry workers with suspected occupational dermatitis, aniline epoxy resins should be considered and patch tested as possible contact allergens. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Chopin-Doroteo, Mario; Salgado-Curiel, Rosa M; Pérez-González, José; Marín-Santibáñez, Benjamín M; Krötzsch, Edgar
2018-06-01
Fibrin and hyaluronic acid are important components of the provisional wound matrix. Through interactions with fibroblasts, they provide biophysical cues that regulate the viscoelastic properties of the extracellular matrix. To understand the roles of fibrin and hyaluronic acid in a collagenous environment, we used fibroblast populated collagen lattices (collagen, collagen-fibrin, and collagen-hyaluronic acid). Compared with collagen and collagen-hyaluronic acid cultures, collagen-fibrin cultures showed less contraction, which is correlated with increased elastic (G') and complex (|G*|) moduli, and reduced proportions of dendritic fibroblasts, despite increased αv integrin expression. Stiffness decreased during culture in collagen-fibrin environment, meanwhile phase shift (δ) values increased, clearly associated with the rise in fibrinolytic and gelatinolytic activities. These processes changed the viscoelastic properties of the system toward G' and |G*| values observed on day 5 in collagen cultures. Although less collagen turnover was observed in collagen-fibrin cultures than in collagen and collagen-hyaluronic acid cultures, collagen neosynthesis was apparently insufficient to contribute to the overall viscoelastic properties of the system. Collagen-hyaluronic acid cultures showed very limited changes during time. Firstly, they exhibited the highest δ values, suggesting an increase in the viscous behavior due to the hygroscopic properties of hyaluronic acid. These results showed that fibrin and hyaluronic acid not only affect differently the viscoelastic properties of the culture, they can tune fibroblastic activity by regulating cell attachment and extracellular matrix remodeling. Copyright © 2018 Elsevier Ltd. All rights reserved.
Pandanaboyana, Sanjay; Bell, Richard; Shah, Nehal; Lodge, J Peter A; Hidalgo, Ernest; Toogood, Giles J; Prasad, K Raj
2017-06-01
There is paucity of data regarding the cost-effectiveness of fibrin sealants during liver surgery. This study aimed to assess the cost-effectiveness of fibrin sealants following right hemihepatectomy for colorectal liver metastases. A prospectively maintained database between 2004 and 2013 was reviewed to identify patients who underwent a right hemihepatectomy with and without fibrin sealant application. Perioperative and post-operative outcomes were analysed to assess its cost-effectiveness. One hundred and sixty-three right hemihepatectomies were performed, of which 79 were in the fibrin sealant treatment group and 84 were in the no sealant group. No difference was seen between fibrin sealant and no sealant with regard to bile leak (P = 0.366), intra-abdominal collections (P = 0.200) and overall post-operative complications (P = 0.480). Operating costs were significantly cheaper in the no sealant group (P = 0.010). There was no difference seen in median post-operative stay between fibrin sealant versus no treatment (8 versus 9 days, P = 0.327), median total bed cost (£3900 versus £4300, P = 0.400), mean transfusion cost per patient (P = 0.201) and overall cost (£6706.15 versus £6555.80, P = 0.792). Fibrin sealant application to cut surface during liver surgery confers no cost benefit and their routine use may not be recommended. © 2014 Royal Australasian College of Surgeons.
[Influence of Gentiana lutea L extract on blood coagulation].
Bakuridze, A D; Nikolaev, S M; Tsagarenshvili, N T; Kurdiani, N G; Mikaia, G A
2009-01-01
The dry extract from the terrestrial parts of Gentiana Lutea was received in accordance to the developed by us general technological scheme. Study of the pharmacological influence of obtained extract on the coagulating properties of blood revealed that after its per os instillation into experimental animals the time of the formation of active thromboplastin reliably increases, while the time of thrombin and fibrinous cluster formation is shortened in comparison with those indices in the animals, that did not receive phyto-preparation, at the same time morphological appearance of the peripheral blood remains unchanged. Dry extract of terrestrial parts of Gentiana Lutea prepared in accordance to the technology recommended by us, together with widely known pharmacological effects, is characterized with new activity - influence on haemostasis. Obtained preliminary data concerning influence of the extract on coagulation of the blood request further deep studies of its mechanism. Revealed new activity of the terrestrial parts of Gentiana Lutea and the studies of the mechanism of its activity will serve in future as a basis for the recommendation of its use in new nosology. Terrestrial parts of Gentiana lutea L. are proposed as an alternative of the underground parts of the plant. Alongside with that, it is expedient to continue the studies devoted to the development of the haemostatic remedies of plant origin with systemic and local action (sponges, films, skin glues) from terrestrial parts of Gentiana lutea L.
Tumturk, Abdulfettah; Ulutabanca, Halil; Gokoglu, Abdulkerim; Oral, Sukru; Menku, Ahmet; Kurtsoy, Ali
2016-01-01
To share the results of conventional surgery in rhinorrhea and the contribution of computerized tomography (CT) cisternography to determination of the site of cerebrospinal fluid (CSF) leak. Twelve cases treated for spontaneous rhinorrhea were included in this study. All the cases underwent cranial CT and magnetic resonance imaging (MRI). CT cisternography was performed in four patients whose bone defect or leakage site could not be detected by CT and MRI. In order to repair the defect, either the galea or galea together with collagen matrix was used and the procedure was supported with fibrin glue. In the cases, postoperative rhinorrhea was seen in neither the early nor the late follow up period. We observed no complications related to CT cisternography or craniotomy. The leakage area was successfully detected with CT cisternography when the other methods failed. Bone defect can usually be shown by means of CT. However, when bone-defect cannot be shown or the dura in the defective area is intact, CT cisternography is useful to show the CSF leak. Conventional surgery was very succesful in the treatment of spontaneous rhinorrhea but it was cosmetically problematic. In the patients both treated with galea and galea together with collagen matrix, the repair of the defect was successful.
Liu, J; Mei, L Y; He, C F; Feng, Y
2016-11-01
Objective: To assess the diversity of spontaneous cerebrospinal fluid(CSF)otorrhear in clinical manifestation,CT,leakage sites and surgical operation between young children and adults. Method: We conducted a retrospective study of 6 consecutive patients who were all underwent the surgery through the transmastoid approach,including 4 adults patients and 2 children.In the 4 adults patients,two patients' bony defects lay on the tegmen mastoideum,one lay on the tegmen tympani,and another one lay on the sinus meningioma angle.None of the 4 adults patients had abnormal inner ear structures.Materials used in repair included free muscle graft,temporalis fascia,and fibrin glue of the 4 adults patients.The 2 children patients were diagnosed with congenital abnormalities of the lateral inner ear,who had bony defects of the foot plate or fenestra vestibule.Materials used in repair included free muscle graft,temporalis fascia,and musclein sequence. Result: No CSF leaks recurred after the operation except one adults patient,who's left ear recurred two times and experienced three operations. Conclusion: The clinical manifestations of spontaneous CSF otorrhea between young children and adults are different,the HRCT scan on temporal bone before the operation is very important.Especially foradults patients,making sure of theleakagesites and numbers isvaluable and significance for thesurgical procedure selection.. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
Treatment of anterior skull base defects by a transnasal endoscopic approach in children.
Di Rocco, Federico; Couloigner, Vincent; Dastoli, Patricia; Sainte-Rose, Christian; Zerah, Michel; Roger, Gilles
2010-11-01
The object of this study was to assess the efficacy and complications of endoscopic management of anterior skull base defects. The authors reviewed the medical records of 28 children (20 boys and 8 girls) undergoing endoscopic repair of anterior skull base defects in their tertiary referral center between 2001 and 2008; 18 cases were congenital and 10 cases posttraumatic. During the endoscopic procedure, rigid telescopes--2.7 or 4 mm in diameter, with 0° or 30° lenses--were used. In 23 patients the anterior skull base defect was sealed with fragments of middle turbinate (bone and mucosa). In the remaining 5 patients it was sealed with cartilage harvested from the nasal septum (3 cases) or from the auricle (2 cases), fibrin glue, and oxidized cellulose. A combined external and endoscopic approach was required in 3 cases because of the size and extensions of the encephalocele. Outcome was primarily assessed by means of clinical examination, nasal fibroscopy, and imaging. The mean duration of follow-up was 26.7 months (range 9-57 months). One patient treated by a combined approach died of meningitis 2 years after surgery. In the remaining 27 patients, there was no recurrence of CSF leak, meningitis, or encephalocele. An iatrogenic frontal or ethmoidal mucocele was observed in 4 cases. The endoscopic approach is a minimally invasive, safe, and efficient technique for removing nasal encephaloceles in children.
Srinivasan, Sathish; Danjoux, Jean-Pierre
2018-01-01
The number of laser in situ keratomileusis (LASIK) procedures is continuing to rise. Since its first application for correcting simple refractive errors over 25 years ago, the role of LASIK has extended to treat other conditions, including postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and presbyopia, among others. The long-term effectiveness, predictability and safety have been well established by many large studies. However, due to the creation of a potential interface between the flap and the underlying stroma, interface complications such as infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an uncommon complication that usually arises during the early postoperative period. The reported incidence of PLEI ranged from 0%–3.9% in primary treatment to 10%–20% in retreatment cases. It can cause a wide spectrum of clinical presentations, ranging from asymptomatic interface changes to severe visual impairment and flap melt requiring keratoplasty. PLEI can usually be treated with mechanical debridement of the affected interface; however, additional interventions, such as alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant, neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be required for recurrent or refractory cases. The aims of this review are to determine the prevalence and risk factors of PLEI; to describe its pathogenesis and clinical features and to summarise the therapeutic armamentarium and the visual outcome of PLEI. PMID:29657982
Ting, Darren Shu Jeng; Srinivasan, Sathish; Danjoux, Jean-Pierre
2018-01-01
The number of laser in situ keratomileusis (LASIK) procedures is continuing to rise. Since its first application for correcting simple refractive errors over 25 years ago, the role of LASIK has extended to treat other conditions, including postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and presbyopia, among others. The long-term effectiveness, predictability and safety have been well established by many large studies. However, due to the creation of a potential interface between the flap and the underlying stroma, interface complications such as infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an uncommon complication that usually arises during the early postoperative period. The reported incidence of PLEI ranged from 0%-3.9% in primary treatment to 10%-20% in retreatment cases. It can cause a wide spectrum of clinical presentations, ranging from asymptomatic interface changes to severe visual impairment and flap melt requiring keratoplasty. PLEI can usually be treated with mechanical debridement of the affected interface; however, additional interventions, such as alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant, neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be required for recurrent or refractory cases. The aims of this review are to determine the prevalence and risk factors of PLEI; to describe its pathogenesis and clinical features and to summarise the therapeutic armamentarium and the visual outcome of PLEI.
Leroyer, C.; Lashéras, A.; Rogues, A.-M.; Darrouzet, V.; Franco-Vidal, V.
2016-01-01
SUMMARY A retroauricular approach is routinely used for treating chronic otitis media. The incidence of surgical site infections after ear surgery is around 10% in contaminated or dirty procedures. This observational prospective study describes surgical site infections after chronic otitis media surgery with the retroauricular approach and investigated their potential predictive factors. This observational prospective study included patients suffering from chronic otitis media and eligible for therapeutic surgery with a retroauricular approach. During follow-up, surgical site infections were defined as "early" if occurring within 30 days after surgery or as "late" if occurring thereafter. The data of 102 patients were analysed. Concerning early surgical site infections, four cases were diagnosed (3.9%) and a significant association was found with preoperative antibiotic therapy, wet ear at pre-operative examination, class III (contaminated) in the surgical wound classification, NNIS (National Nosocomial Infection Surveillance) index > 1, and oral post-operative antibiotic use. Seven late surgical site infections were diagnosed (7.1%) between 90 and 160 days after surgery and were significantly correlated to otorrhoea during the 6 months before surgery, surgery duration ≤60 minutes, canal wall down technique and use of fibrin glue. Surgical site infections after chronic otitis media surgery seem to be associated with factors related to the inflammatory state of the middle ear at the time of surgery in early infections and with chronic inflammation in late infections. PMID:27196077
EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair.
Tao, Xu; Liu, Junpeng; Chen, Lei; Zhou, You; Tang, Kanglai
2015-01-01
The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.
Pretorius, Etheresia; du Plooy, Jenny; Soma, Prashilla; Gasparyan, Armen Yuri
2014-07-01
The study suggests that patients with systemic lupus erythematosus (SLE) present with distinct inflammatory ultrastructural changes such as platelets blebbing, generation of platelet-derived microparticles, spontaneous formation of massive fibrin network and fusion of the erythrocytes membranes. Lupoid platelets actively interact with other inflammatory cells, particularly with white blood cells (WBCs), and the massive fibrin network facilitates such an interaction. It is possible that the concerted actions of platelets, erythrocytes and WBC, caught in the inflammatory fibrin network, predispose to pro-thrombotic states in patients with SLE.
Roura, Santiago; Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Férnandez, Marco A; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Perea-Gil, Isaac; Blanco, Jerónimo; Bayes-Genis, Antoni
2015-08-01
Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound. ©AlphaMed Press.
Antibiotic-primed fibrin gel improves outcome in contaminated splenic injury.
Ing, R D; Saxe, J; Hendrick, S; Bailey, J; Diebel, L N; Dulchavsky, S A; Brown, W
1992-07-01
Fibrin gel (FG) has recently been shown to be bactericidal in the management of contaminated hepatic injury; antibiotic loading of fibrin gel (AFG) may augment this effect. We evaluated the antimicrobial properties of FG and AFG in a rat model of contaminated splenic injury. Fibrin gel was made from centrifuged plasma of separate donor rats and bovine thrombin. Antibiotic fibrin gel was similarly produced following intravenous injection of 70 mg/kg ticarcillin. Male Holtzman rats (250-300 g) were anesthetized and a laparotomy done. The abdomen was contaminated with 1 x 10(7) Bacteroides fragilis and the spleen transected in the midportion. Treatment consisted of splenorrhaphy (S) (n = 7), FG application (n = 7), or AFG (n = 7). The animals were autopsied at 1 week to evaluate abscess formation and abdominal adhesions (grade I = none, grade II = mild, grade III = severe). Antibiotic/fibrin gel significantly decreased abscess formation following splenic injury when compared with S (2 of 7 vs. 7 of 7; p less than 0.05 by ANOVA) without an increase in adhesions. Fibrin gel also decreased abscess formation but not significantly (4 of 7 vs. 7 of 7). Histologic analysis confirmed the beneficial effect of FG and AFG on wound healing. The bactericidal effect of FG is improved by antibiotic loading in contaminated intraabdominal injury.
Ko, Ya-Ping; Flick, Matthew J.
2017-01-01
Fibrinogen not only plays a pivotal role in hemostasis but also serves key roles in antimicrobial host defense. As a rapidly assembled provisional matrix protein, fibrin(ogen) can function as an early line of host protection by limiting bacterial growth, suppressing dissemination of microbes to distant sites, and mediating host bacterial killing. Fibrinogen-mediated host antimicrobial activity occurs predominantly through two general mechanisms, namely, fibrin matrices functioning as a protective barrier and fibrin(ogen) directly or indirectly driving host protective immune function. The potential of fibrin to limit bacterial infection and disease has been countered by numerous bacterial species evolving and maintaining virulence factors that engage hemostatic system components within vertebrate hosts. Bacterial factors have been isolated that simply bind fibrinogen or fibrin, promote fibrin polymer formation, or promote fibrin dissolution. Staphylococcus aureus is an opportunistic gram-positive bacterium, the causative agent of a wide range of human infectious diseases, and a prime example of a pathogen exquisitely sensitive to host fibrinogen. Indeed, current data suggest fibrinogen serves as a context-dependent determinant of host defense or pathogen virulence in Staphylococcus infection whose ultimate contribution is dictated by the expression of S. aureus virulence factors, the path of infection, and the tissue microenvironment. PMID:27056151
Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin.
Amelot, Aymeric A; Tagzirt, Madjid; Ducouret, Guylaine; Kuen, René Lai; Le Bonniec, Bernard F
2007-01-05
Platelet factor-4 (PF4/CXCL4) is an orphan chemokine released in large quantities in the vicinity of growing blood clots. Coagulation of plasma supplemented with a matching amount of PF4 results in a translucent jelly-like clot. Saturating amounts of PF4 reduce the porosity of the fibrin network 4.4-fold and decrease the values of the elastic and loss moduli by 31- and 59-fold, respectively. PF4 alters neither the cleavage of fibrinogen by thrombin nor the cross-linking of protofibrils by activated factor XIII but binds to fibrin and dramatically transforms the structure of the ensuing network. Scanning electron microscopy showed that PF4 gives rise to a previously unreported pattern of polymerization where fibrin assembles to form a sealed network. The subunits constituting PF4 form a tetrahedron having at its corners a RPRH motif that mimics (in reverse orientation) the Gly-His-Arg-Pro-amide peptides that co-crystallize with fibrin. Molecular modeling showed that PF4 could be docked to fibrin with remarkable complementarities and absence of steric clashes, allowing the assembly of irregular polymers. Consistent with this hypothesis, as little as 50 microm the QVRPRHIT peptide derived from PF4 affects the polymerization of fibrin.
Spotnitz, William D.
2014-01-01
Background. Fibrin sealant became the first modern era material approved as a hemostat in the United States in 1998. It is the only agent presently approved as a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The product is now supplied as patches in addition to the original liquid formulations. Both laboratory and clinical uses of fibrin sealant continue to grow. The new literature on this material also continues to proliferate rapidly (approximately 200 papers/year). Methods. An overview of current fibrin sealant products and their approved uses and a comprehensive PubMed based review of the recent literature (February 2012, through March 2013) on the laboratory and clinical use of fibrin sealant are provided. Product information is organized into sections based on a classification system for commercially available materials. Publications are presented in sections based on both laboratory research and clinical topics are listed in order of decreasing frequency. Results. Fibrin sealant remains useful hemostat, sealant, and adhesive. New formulations and applications continue to be developed. Conclusions. This agent remains clinically important with the recent introduction of new commercially available products. Fibrin sealant has multiple new uses that should result in further improvements in patient care. PMID:24729902
He, S; Ekman, G Jacobsson; Hedner, U
2005-02-01
Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)- and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 microg mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 microg mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at least down to 20 x 10(6) mL(-1). The effect of rFVIIa was not observed when unfrozen platelets instead of frozen-thawed platelets were added. Neither was any effect on the fibrin permeability seen, in the presence of annexin V, known to block the effect of phospholipids on the platelet surface. This indicates an important role of platelet phospholipids for the effect of rFVIIa. A similar effect on the fibrin permeability of rFVIIa was observed when added to platelet-rich plasma from a patient with Glanzmann thrombasthenia. Recombinant FVIIa has been found to induce hemostasis in patients with hemophilia and inhibitors against FVIII/FIX as well as in patients with Glanzmann thrombasthenia, indicating the importance of the formation of a tight fibrin gel structure, more resistant against premature proteolysis, for maintaining hemostasis. In conclusion, the addition of rFVIIa (5 microg mL(-1)) also substantially decreased the permeability constant of fibrin gels formed in FVIII-deficient plasma in the presence of low numbers of frozen-thawed platelets (down to 20 x 10(6) mL(-1)). A similar pattern was obtained in plasma from a Glanzmann patient. No effect was found in the presence of unfrozen instead of frozen-thawed platelets. Annexin V blocked any effect of rFVIIa. A normalization of the overall fibrinolysis potential (OFP) during the same condition supports the effect of rFVIIa on the fibrin permeability in the presence of a limited number of platelets.
Spiritual and Religious Supports Part 8: Church G.L.U.E.
ERIC Educational Resources Information Center
Newman, Barbara J.
2009-01-01
CLC Network is an organization that partners with churches, schools, and families to help promote and build inclusive and interdependent communities for those with disabilities. This article describes CLC Network's most recent tool--a book entitled the G.L.U.E. Training Manual. G.L.U.E. is an adhesive process to allow each individual to be firmly…
Mullaguri, Harish; Suresh, Nandini; Surendran, Smitha; Velmurugan, Natanasabapathy; Chitra, Selvarajan
2016-05-01
The purpose of this study was to evaluate the influence of pH that is due to setting reaction of Biodentine, glass ionomer cement (GIC), and intermediate restorative material (IRM) on transforming growth factor-β1 (TGF-β1) release and on the fibrin architecture of platelet-rich fibrin (PRF). PRF was obtained from 8 volunteers and layered over the freshly prepared GIC, IRM, and Biodentine mixtures. TGF-β1 release was estimated by using enzyme-linked immunosorbent assay (ELISA), and fibrin structure of PRF was analyzed by using scanning electron microscope at 1 and 5 hours. Biodentine, GIC, and IRM increased the TGF-β1 release in comparison with that of control group (PRF alone) at both 1 and 5 hours. Biodentine released significantly more TGF-β1 than GIC and IRM at 1 hour. At 5 hours both GIC and Biodentine released significantly more TGF-β1 than IRM. The fibrin architecture of the Biodentine group was similar to that of control group at both 1 and 5 hours. In GIC and IRM groups the fibrillar structure of fibrin was collapsed, ill-defined, and cloudy with very thick fibers and irregularly reduced porosities. Biodentine induces larger amount of TGF-β1 release and also maintains the integrity of fibrin structure when compared with GIC and IRM when layered over PRF. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
Deposition of Fibrinogen on the Surface of in vitro Thrombi Prevents Platelet Adhesion
Owaynat, Hadil; Yermolenko, Ivan S.; Turaga, Ramya; Lishko, Valeryi K.; Sheller, Michael R.; Ugarova, Tatiana P.
2015-01-01
The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion. PMID:26482763
Chignon-Sicard, Bérengère; Georgiou, Charalambos A; Fontas, Eric; David, Sylvain; Dumas, Pierre; Ihrai, Tarik; Lebreton, Elisabeth
2012-12-01
Application of platelet concentrates to wounds could speed healing. Leukocyte- and platelet-rich fibrin, a relatively recent development, stands out from the other preparations. This prospective, randomized, controlled clinical trial studied the rate of healing of postoperative hand wounds after a single application of leukocyte- and platelet-rich fibrin. Eligible patients were healthy individuals older than 18 years who had been scheduled for elective McCash (open palm) surgery for Dupuytren disease at the Plastic and Hand Surgery Department of Nice's University Hospital between August of 2007 and February of 2010. The control group received the reference care of petroleum jelly mesh (Vaselitulle), and test patients had leukocyte- and platelet-rich fibrin applied. The primary endpoint was healing delay measured in postoperative days. Secondary endpoints included pain, bleeding, and wound exudate. The trial was carried out as a single-blind trial. Among the 68 randomized patients, 33 patients in the leukocyte- and platelet-rich fibrin group and 31 in the Vaselitulle group were analyzed. Primary endpoint analysis showed a median healing delay of 24 days (interquartile range, 18 to 28 days) for the fibrin group and 29 days (interquartile range, 26 to 35 days) for the Vaselitulle group (p = 0.014, log-rank test). Postoperative pain assessment, bleeding, and exudate were always lower for the fibrin group, but not significantly so. The authors trial demonstrates that a single leukocyte- and platelet-rich fibrin application on fresh postoperative hand wounds shows a median improvement of 5 days in comparison with the standard treatment. Therapeutic, II.
Deposition of fibrinogen on the surface of in vitro thrombi prevents platelet adhesion.
Owaynat, Hadil; Yermolenko, Ivan S; Turaga, Ramya; Lishko, Valeryi K; Sheller, Michael R; Ugarova, Tatiana P
2015-12-01
The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion. Copyright © 2015 Elsevier Ltd. All rights reserved.
Lytic and mechanical stability of clots composed of fibrin and blood vessel wall components.
Rottenberger, Z; Komorowicz, E; Szabó, L; Bóta, A; Varga, Z; Machovich, R; Longstaff, C; Kolev, K
2013-03-01
Proteases expressed in atherosclerotic plaque lesions generate collagen fragments, release glycosaminoglycans (chondroitin sulfate [CS] and dermatan sulfate [DS]) and expose extracellular matrix (ECM) proteins (e.g. decorin) at sites of fibrin formation. Here we address the effect of these vessel wall components on the lysis of fibrin by the tissue plasminogen activator (tPA)/plasminogen system and on the mechanical stability of clots. MMP-8-digested collagen fragments, isolated CS, DS, glycosylated decorin and its core protein were used to prepare mixed matrices with fibrin (additives present at a 50-fold lower mass concentration than fibrinogen). Scanning electron microscopy (SEM) showed that the presence of ECM components resulted in a coarse fibrin structure, most pronounced for glycosylated decorin causing an increase in the median fiber diameter from 85 to 187 nm. Rheological measurements indicated that these structural alterations were coupled to decreased shear resistance (1.8-fold lower shear stress needed for gel/fluid transition of the clots containing glycosylated decorin) and rigidity (reduction of the storage modulus from 54.3 to 33.2 Pa). The lytic susceptibility of the modified fibrin structures was increased. The time to 50% lysis by plasmin was reduced approximately 2-fold for all investigated ECM components (apart from the core protein of decorin which produced a moderate reduction of the lysis time by 25%), whereas fibrin-dependent plasminogen activation by tPA was inhibited by up to 30%. ECM components compromise the chemical and mechanical stability of fibrin as a result of changes in its ultrastructure. © 2012 International Society on Thrombosis and Haemostasis.
Al-Batanony, M A; Abdel-Rasoul, G M; Abu-Salem, M A; Al-Ahmar, I A; Al-Badry, A S
2012-04-01
Glues are strong, liquid adhesive derived from animal tissues. It has been shown that glue sniffing is associated with demyelinating polyneuropathy. The low molecular weight agents which cause occupational lung disease have generally included the isocyanates exposure to which could result in asthma among workers. Toluene is also used widely in glue and adhesive industry and households where toluene exposure and abuse can occur. To study some respiratory and neurological disorders that may arise in workers in a bone glue factory in Queisna industrial zone, Menoufyia governorate, Egypt. In a historical cohort study, the exposed participants (n = 50) were recruited from workers in a bone glue factory in Queisna industrial zone, Menoufyia governorate. The unexposed group was selected from workers' relatives who had never worked in glue industry. All participants completed a pre-designed questionnaire on personal and occupational histories. Pulmonary function tests as well as electromyography (EMG) were performed for all participants. Urinary hippuric acid was also measure in all participants. The prevalence of cough, asthmatic attacks and paresthesia were significantly higher among exposed than unexposed participants. Abnormal spirometric measurements (particularly towards obstruction), abnormal EMG and positive urinary hippuric acid were significantly more prevalent among exposed than unexposed group. Spirometry and EMG should be included in the periodic medical examination for exposed workers for early detection of respiratory and neurological disorders. Urinary hippuric acid could be a useful indicator of the nerve conduction abnormalities and should be measured periodically for these workers.
Fahed, Robert; Clarençon, Frédéric; Sourour, Nader-Antoine; Chauvet, Dorian; Le Jean, Lise; Chiras, Jacques; Di Maria, Federico
2016-07-01
One of the procedural risks in arteriovenous malformation (AVM) embolization is possible migration of the embolic agent into the venous drainage with an incomplete nidus occlusion, which may lead to severe hemorrhagic complications. This report presents the case of a 29-year-old man who presented with a deep intraparenchymal hematoma on the left side secondary to the spontaneous rupture of a claustral AVM. Upon resorption of the hematoma, the patient underwent an initial therapeutic session of N-butyl-2 cyanoacrylate endovascular embolization, with the purpose of reducing the AVM volume and flow before performing Gamma Knife radiosurgery. After glue injection into one of the arterial feeders, the control angiography showed a partial migration of the glue cast into the straight sinus, with most of the nidus still visible. Because of the bleeding risk due to possible venous hypertension, it was decided to try to retrieve the glue from the vein by using a stent retriever via jugular access. This maneuver allowed a nearly complete removal of the glue cast, thereby restoring normal venous flow drainage. The patient showed no clinical worsening after the procedure. To the authors' knowledge, this is the first report of the use of the Solitaire FR device as a rescue glue retriever. This method should be considered by physicians in cases of unintended glue migration into the venous circulation during AVM embolization.
Srinivas, B. V. V.; Rupa, N.; Halini Kumari, K. V.; Rajender, A.; Reddy, M. Narendra
2015-01-01
Periodontal plastic surgery is the branch of periodontology that is focused mainly on the correction or elimination of mucogingival problems associated with lack of attached gingiva, a shallow vestibule and aberrant frenum. Various mucogingival surgical procedures are used to halt the progression of the gingival recession and to correct poor esthetic appearance. Free gingival autograft is one of the most common techniques used for a gingival recession in areas of inadequate attached gingiva in the mandibular anterior region. Fibrin sealants are human plasma derivatives that mimic the final stages of blood coagulation, forming a fibrin clot. Fibrin Sealants enhances the overall outcome of surgical intervention because of their hemostatic, adhesive, and healing properties. These properties of fibrin sealants may reduce operating time, prevent complications, and enhance the overall outcome of many surgical interventions. Hence, this case report aims to investigate the clinical effectiveness of free gingival graft along with the commercially available fibrin-fibronectin sealing system (Tissucol®) in the treatment of Miller's class II gingival recession. PMID:26538956
di Lauro, A E; Abbate, D; Dell'Angelo, B; Iannaccone, G A; Scotto, F; Sammartino, G
2015-11-02
Leukocyte-platelet rich fibrin belongs to a second generation of platelet concentrates that does not need biochemical blood manipulation. It is used for tissue healing and regeneration in periodontal and oral-maxillofacial surgery. We report two cases of hyperplastic gingival lesions treated by exeresis and application of leukocyte-platelet rich fibrin membranes in order to improve and accelerate tissue healing. Two patients (a 78-year-old Caucasian woman and a 30-year-old Caucasian man) were treated for hyperplastic gingival lesions. They underwent to exeresis of lesions and application of leukocyte-platelet rich fibrin membranes. Tissue healing was clinically evaluated after 1, 3, 7, 14 and 30 postoperative days. No recurrences were observed after 2 years of semi-annual follow up. We obtained rapid and good healing of soft tissues probably due to the elevated content of leukocytes, platelets and growth factors in the leukocyte-platelet rich fibrin. Based on our results we suggest the use of leukocyte-platelet rich fibrin to cover wounds after exeresis of oral neoformations such as hyperplastic gingival lesions.
A method to determine shear adhesive strength of fibrin sealants.
Sierra, D H; Feldman, D S; Saltz, R; Huang, S
1992-01-01
The adhesive strength of fibrin sealants has not been rigorously evaluated to date. The adhesive strength of six different concentrations of cryoprecipitated fibrinogen as well as the commercially available fibrin tissue adhesive Tissucol was tested under controlled conditions utilizing split-thickness skin grafts as the test adherand. This test configuration permitted the modeling of bonding strength for attachment of skin grafts as well as incorporate established engineering test standards for adhesives. An increase in fibrin concentration corresponded with an increase in shear adhesive strength. No significant increases in adhesive strength were attained after 5 min of bonding for all tested concentrations, except for the commercial adhesive, which attained the adhesive strength of an equivalent concentration of cryoprecipitated adhesive after 90 min. The adhesive strength, however, was an order of magnitude less than reported values of the tensile strength of fibrin material for similar concentrations. Therefore, it is important that the surgeon use a sufficiently high fibrinogen concentration for the specific clinical indication. The method of fibrin sealant preparation and/or the compounding adjuncts appear to have an effect on the development of adhesive strength.
Watertight cataract incision closure using fibrin tissue adhesive.
Hovanesian, John A; Karageozian, Vicken H
2007-08-01
To determine whether a simple method for applying fibrin tissue adhesive to a clear corneal cataract incision can create a watertight seal. Laboratory investigation. Clear corneal cataract incisions were simulated in 8 eye-bank eyes. In 4 eyes, fibrin adhesive was applied to the incision in a simple manner; the other 4 eyes were controls with no adhesive. Each eye was tested under low pressure conditions to detect fluid ingress of India Ink on the eye's surface. The eyes were tested again with external compression to distort the incision to detect fluid egress. In the eyes with fibrin adhesive, there was no egress of fluid with incision distortion and no ingress of India Ink. In the 4 eyes without adhesive, there was ingress and egress of fluid. A simple method of applying fibrin adhesive to cataract incisions created a watertight seal.
CYLD Enhances Severe Listeriosis by Impairing IL-6/STAT3-Dependent Fibrin Production
Nishanth, Gopala; Deckert, Martina; Wex, Katharina; Massoumi, Ramin; Schweitzer, Katrin; Naumann, Michael; Schlüter, Dirk
2013-01-01
The facultative intracellular bacterium Listeria monocytogenes (Lm) may cause severe infection in humans and livestock. Control of acute listeriosis is primarily dependent on innate immune responses, which are strongly regulated by NF-κB, and tissue protective factors including fibrin. However, molecular pathways connecting NF-κB and fibrin production are poorly described. Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-κB-dependent immune responses, regulated these protective host responses in murine listeriosis. Upon high dose systemic infection, all C57BL/6 Cyld−/− mice survived, whereas 100% of wildtype mice succumbed due to severe liver pathology with impaired pathogen control and hemorrhage within 6 days. Upon in vitro infection with Lm, CYLD reduced NF-κB-dependent production of reactive oxygen species, interleukin (IL)-6 secretion, and control of bacteria in macrophages. Furthermore, Western blot analyses showed that CYLD impaired STAT3-dependent fibrin production in cultivated hepatocytes. Immunoprecipitation experiments revealed that CYLD interacted with STAT3 in the cytoplasm and strongly reduced K63-ubiquitination of STAT3 in IL-6 stimulated hepatocytes. In addition, CYLD diminished IL-6-induced STAT3 activity by reducing nuclear accumulation of phosphorylated STAT3. In vivo, CYLD also reduced hepatic STAT3 K63-ubiquitination and activation, NF-κB activation, IL-6 and NOX2 mRNA production as well as fibrin production in murine listeriosis. In vivo neutralization of IL-6 by anti-IL-6 antibody, STAT3 by siRNA, and fibrin by warfarin treatment, respectively, demonstrated that IL-6-induced, STAT3-mediated fibrin production significantly contributed to protection in Cyld−/− mice. In addition, in vivo Cyld siRNA treatment increased STAT3 phosphorylation, fibrin production, pathogen control and survival of Lm-infected WT mice illustrating that therapeutic inhibition of CYLD augments the protective NF-κB/IL-6/STAT3 pathway and fibrin production. PMID:23825949
CYLD enhances severe listeriosis by impairing IL-6/STAT3-dependent fibrin production.
Nishanth, Gopala; Deckert, Martina; Wex, Katharina; Massoumi, Ramin; Schweitzer, Katrin; Naumann, Michael; Schlüter, Dirk
2013-01-01
The facultative intracellular bacterium Listeria monocytogenes (Lm) may cause severe infection in humans and livestock. Control of acute listeriosis is primarily dependent on innate immune responses, which are strongly regulated by NF-κB, and tissue protective factors including fibrin. However, molecular pathways connecting NF-κB and fibrin production are poorly described. Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-κB-dependent immune responses, regulated these protective host responses in murine listeriosis. Upon high dose systemic infection, all C57BL/6 Cyld(-/-) mice survived, whereas 100% of wildtype mice succumbed due to severe liver pathology with impaired pathogen control and hemorrhage within 6 days. Upon in vitro infection with Lm, CYLD reduced NF-κB-dependent production of reactive oxygen species, interleukin (IL)-6 secretion, and control of bacteria in macrophages. Furthermore, Western blot analyses showed that CYLD impaired STAT3-dependent fibrin production in cultivated hepatocytes. Immunoprecipitation experiments revealed that CYLD interacted with STAT3 in the cytoplasm and strongly reduced K63-ubiquitination of STAT3 in IL-6 stimulated hepatocytes. In addition, CYLD diminished IL-6-induced STAT3 activity by reducing nuclear accumulation of phosphorylated STAT3. In vivo, CYLD also reduced hepatic STAT3 K63-ubiquitination and activation, NF-κB activation, IL-6 and NOX2 mRNA production as well as fibrin production in murine listeriosis. In vivo neutralization of IL-6 by anti-IL-6 antibody, STAT3 by siRNA, and fibrin by warfarin treatment, respectively, demonstrated that IL-6-induced, STAT3-mediated fibrin production significantly contributed to protection in Cyld(-/-) mice. In addition, in vivo Cyld siRNA treatment increased STAT3 phosphorylation, fibrin production, pathogen control and survival of Lm-infected WT mice illustrating that therapeutic inhibition of CYLD augments the protective NF-κB/IL-6/STAT3 pathway and fibrin production.
Podolnikova, Nataly P.; Yakovlev, Sergiy; Yakubenko, Valentin P.; Wang, Xu; Gorkun, Oleg V.; Ugarova, Tatiana P.
2014-01-01
The currently available antithrombotic agents target the interaction of platelet integrin αIIbβ3 (GPIIb-IIIa) with fibrinogen during platelet aggregation. Platelets also bind fibrin formed early during thrombus growth. It was proposed that inhibition of platelet-fibrin interactions may be a necessary and important property of αIIbβ3 antagonists; however, the mechanisms by which αIIbβ3 binds fibrin are uncertain. We have previously identified the γ370–381 sequence (P3) in the γC domain of fibrinogen as the fibrin-specific binding site for αIIbβ3 involved in platelet adhesion and platelet-mediated fibrin clot retraction. In the present study, we have demonstrated that P3 can bind to several discontinuous segments within the αIIb β-propeller domain of αIIbβ3 enriched with negatively charged and aromatic residues. By screening peptide libraries spanning the sequence of the αIIb β-propeller, several sequences were identified as candidate contact sites for P3. Synthetic peptides duplicating these segments inhibited platelet adhesion and clot retraction but not platelet aggregation, supporting the role of these regions in fibrin recognition. Mutant αIIbβ3 receptors in which residues identified as critical for P3 binding were substituted for homologous residues in the I-less integrin αMβ2 exhibited reduced cell adhesion and clot retraction. These residues are different from those that are involved in the coordination of the fibrinogen γ404–411 sequence and from auxiliary sites implicated in binding of soluble fibrinogen. These results map the binding of fibrin to multiple sites in the αIIb β-propeller and further indicate that recognition specificity of αIIbβ3 for fibrin differs from that for soluble fibrinogen. PMID:24338009
Jenkins, Julia; Modarai, Bijan; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Grover, Steven P.; Patel, Ashish S.; Schaeffter, Tobias; Smith, Alberto; Botnar, Rene M.
2014-01-01
Objective Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus’ fibrin content in vivo and for the identification of thrombus suitable for thrombolysis. Approach and Results Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus’ histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R2=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre–EP-2104R and post–EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97–1.00] and 0.994 [95% confidence interval, 0.98–1.00] respectively). Conclusions MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. PMID:24723557
Evaluation of thrombelastographic platelet-mapping in healthy cats.
Blois, Shauna L; Banerjee, Amrita; Wood, R Darren
2012-06-01
Thrombelastography (TEG) permits analysis of clot formation but it is not specific for platelet activity. TEG PlateletMapping (TEG-PM) is a modification of TEG that uses adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet agonists to define the contribution of platelets to clot formation. The objectives of this study were to determine values for TEG-PM in healthy cats and the interassay variation of TEG-PM. TEG-PM analysis was performed on blood specimens collected from 12 healthy cats and was repeated using a second blood specimen collected 2 hours later. Maximum amplitudes generated by thrombin (MA(thrombin)), fibrin (MA(fibrin)), ADP-stimulated platelet activity (MA(ADP)), and AA-stimulated platelet activity (MA(AA)) were recorded. Mean ± SD for MA(thrombin) was 51.1 ± 8.5 mm, for MA(fibrin) was 32.3 ± 17.7 mm, for MA(ADP) was 32.3 ± 15.0 mm, and for MA(AA) was 24.5 ± 12.2 mm. Mean MA(ADP) and MA(fibrin) were not significantly different, whereas mean MA(AA) was significantly lower than mean MA(fibrin). Results from the first and second specimens were not significantly different. Correlation between the first and second specimens was moderate for MA(thrombin), MA(fibrin), and MA(ADP), but was poor for MA(AA). A high degree of variability (coefficient of variation 47.7-60.0%) was observed for MA(fibrin), MA(ADP), and MA(AA). As MA(ADP) and MA(AA) (AA) were the same as or lower than MA(fibrin), a valid baseline to determine platelet-stimulated clot formation could not be established. Considerable interassay variation and wide intervals for MA(fibrin), MA(ADP), and MA(AA) values in this study indicate that TEG-PM should be used cautiously in feline patients. Several preanalytical factors should be examined in further detail. © 2012 American Society for Veterinary Clinical Pathology.
Zhang, Zhimin; Liu, Jian; Meng, Guolin; Wu, Yaoping
2008-03-01
To explore the preventing effects of TGF-beta1 antibody (TGF-beta1Ab) compounded with fibrin glue (FG) on postoperative adhesions of flexor tendon. Seventy-two Leghorn chickens were randomly divided into 4 groups (groups A, B, C and D), 18 chickens for each group, and the long flexor tendons of the 3rd and 4th toes in zone II of all chickens were transversed and sutured with the 4-strand cruciate repair technique to make defect models. In group A, 0.2 mL TGF-beta1 Ab was applied at repair site. In group B, 0.2 mL FG was applied at repair site. In group C, 0.2 mL TGF-beta1Ab and FG was applied at repair site. In group D, 0.2 mL normal sodium was applied at repair site. At 1, 3 and 8 weeks after operation, the tendons of 6 chickens in each group were harvested for morphological and histological evaluation. Six specimens of each group were obtained for biomechanical test at 3 and 8 weeks. The gross-observation showed that the differences in grading of tendon adhesion were not significant among 4 groups at 1 week after operation (P > 0.05), but the differences were significant between groups A, B, D and group C at 3 and 8 weeks after operation (P < 0.05). Histological observation showed that collagen fibers arranged irregularly in groups A, B and D, but arranged regularly in group C at 3 and 8 weeks' after operation. At 3 weeks after operation the gliding excursion ratio of the tendon in groups A, B, C and D were 0.45 +/- 0.05, 0.40 +/- 0.10, 0.79 +/- 0.09 and 0.25 +/- 0.07 respectively; the simulated active flexion ratio were 0.61 +/- 0.02, 0.67 +/- 0.03, 0.91 +/- 0.03 and 0.53 +/- 0.04 respectively; the work of flexion were (18.00 +/- 0.77), (17.80 +/- 1.13), (27.60 +/- 1.73) and (15.60 +/- 1.27) degrees/N respectively. There were significant differences between group C and other three groups (P < 0.05). The tendon anastomosis breaking strength were (14.2 +/- 1.9), (15.2 +/- 2.2), (16.0 +/- 2.2) and (14.7 +/- 2.7) N, showing no significant differences among 4 groups (P > 0.05). At 8 weeks after operation, the gliding excursion ratio of the tendon in groups A, B, C and D were 0.45 +/- 0.07, 0.43 +/- 0.08, 0.80 +/- 0.09 and 0.29 +/- 0.05 respectively; the simulated active flexion ratio were 0.61 +/- 0.02, 0.63 +/- 0.03, 0.92 +/- 0.03 and 0.53 +/- 0.03 respectively, the work of flexion were (18.30 +/- 0.84), (18.60 +/- 0.80), (27.90 +/- 1.24) and (15.30 +/- 0.75) degrees/N respectively. There were significant differences between group C and other three groups (P < 0.05). The tendon anastomosis breaking strength were(51.9 +/- 3.0), (51.4 +/- 1.4), (53.3 +/- 1.3) and (52.3 +/- 2.2) N, showing no significant differences among 4 groups (P > 0.05). TGF-beta1Ab compounded with FG could significantly prohibit the formation of fibrous adhesions without interfering with the healing process.
Mischke, R; Wohlsein, P; Schoon, H-A
2005-01-01
The objective of the study was to examine the alterations of fibrin generation in dogs with haemangiosarcoma using resonance thrombography. The second objective was to evaluate the sensitivity of this method for the detection of hypofibrinogenaemia and/or increased fibrin(ogen) degradation product (FDP) concentration. Resonance thrombogram (RTG) measurements with two different instruments were performed in 30 unselected dogs with haemangiosarcoma, 14 of which had decreased fibrinogen and 28 of which had an increased FDP concentration (p<0.0001). The RTG-reaction time was less sensitive than the fibrin formation time (RTG-f) and fibrin amplitude (RTG-F). The RTG-f and RTG-F indicated reliably a decrease in fibrinogen concentration (sensitivity: 0.93). The sensitivity of detection of increased FDP levels was considerably higher than that of thrombin time. However, false-negative results were found even at FDP concentrations > or =120 mg/l, especially in cases with high fibrinogen level. Both machines showed similar sensitivity. The results of this study indicate that canine haemangiosarcoma is frequently associated with severe alterations of fibrin generation due to low fibrinogen and high FDP levels leading to distinct RTG abnormalities. The global test RTG reacts sensitively to a decreased fibrinogen level whereas its accuracy to detect FDP concentrations occurring under pathophysiological conditions is limited. A significant alteration of fibrin generation induced by FDPs may not occur until the serum FDP concentration exceeds 60 mg/l.
Cosemans, Judith M. E. M.; Schols, Saskia E. M.; Stefanini, Lucia; de Witt, Susanne; Feijge, Marion A. H.; Hamulyák, Karly; Deckmyn, Hans; Bergmeier, Wolfgang
2011-01-01
A microscopic method was developed to study the role of platelets in fibrin formation. Perfusion of adhered platelets with plasma under coagulating conditions at a low shear rate (250−1) resulted in the assembly of a star-like fibrin network at the platelet surface. The focal fibrin formation on platelets was preceded by rises in cytosolic Ca2+, morphologic changes, and phosphatidylserine exposure. Fibrin formation was slightly affected by αIIbβ3 blockage, but it was greatly delayed and reduced by the following: inhibition of thrombin or platelet activation; interference in the binding of von Willebrand factor (VWF) to glycoprotein Ib/V/IX (GpIb-V-IX); plasma or blood from patients with type 1 von Willebrand disease; and plasma from mice deficient in VWF or the extracellular domain of GpIbα. In this process, the GpIb-binding A1 domain of VWF was similarly effective as full-length VWF. Prestimulation of platelets enhanced the formation of fibrin, which was abrogated by blockage of phosphatidylserine. Together, these results show that, in the presence of thrombin and low shear flow, VWF-induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. This process can be relevant in hemostasis and the manifestation of von Willebrand disease. PMID:21037087
A novel platelet concentrate: titanium-prepared platelet-rich fibrin.
Tunalı, Mustafa; Özdemir, Hakan; Küçükodacı, Zafer; Akman, Serhan; Yaprak, Emre; Toker, Hülya; Fıratlı, Erhan
2014-01-01
We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF). The T-PRF method is based on the hypothesis that titanium may be more effective in activating platelets than the silica activators used with glass tubes in Chouckroun's leukocyte- and platelet-rich fibrin (L-PRF) method. In this study, we aimed to define the structural characteristics of T-PRF and compare it with L-PRF. Blood samples were collected from 10 healthy male volunteers. The blood samples were drawn using a syringe. Nine milliliters was transferred to a dry glass tube, and 9 mL was transferred to a titanium tube. Half of each clot (i.e., the blood that was clotted using T-PRF or L-PRF) was processed with a scanning electron microscope (SEM). The other half of each clot was processed for fluorescence microscopy analysis and light microscopy analysis. The T-PRF samples seemed to have a highly organized network with continuous integrity compared to the other L-PRF samples. Histomorphometric analysis showed that T-PRF fibrin network covers larger area than L-PRF fibrin network; also fibrin seemed thicker in the T-PRF samples. This is the first human study to define T-PRF as an autogenous leukocyte- and platelet-rich fibrin product. The platelet activation by titanium seems to offer some high characteristics to T-PRF.
Briquez, Priscilla S; Lorentz, Kristen M; Larsson, Hans M; Frey, Peter; Hubbell, Jeffrey A
2017-08-01
Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of aprotinin. Here, we aimed to develop a human-derived substitute to aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as aprotinin's is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro, outperforming aprotinin. In vivo, our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which aprotinin did not show efficacy, thus qualifying it as a competitive substitute of aprotinin in fibrin sealants. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.
Pawelec, K M; Wardale, R J; Best, S M; Cameron, R E
2015-01-01
Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs.
Cytotoxic T Lymphocyte Trafficking and Survival in an Augmented Fibrin Matrix Carrier
Zou, Zhaoxia; Denny, Erin; Brown, Christine E.; Jensen, Michael C.; Li, Gang; Fujii, Tatsuhiro; Neman, Josh; Jandial, Rahul; Chen, Mike
2012-01-01
Cell-based therapies have intriguing potential for the treatment of a variety of neurological disorders. One such example is genetically engineered cytotoxic T lymphocytes (CTLs) that are being investigated in brain tumor clinical trials. The development of methods for CTL delivery is critical to their use in the laboratory and clinical setting. In our study, we determined whether CTLs can migrate through fibrin matrices and if their migration, survival, and function could be modulated by adding chemokines to the matrix. Our results indicated that CTLs can freely migrate through fibrin matrices. As expected, the addition of the monocyte chemotactic protein-1 (MCP-1), also known as chemokine C-C motif ligand 2 (CCL2), to the surrounding media increased egress of the CTLs out of the fibrin clot. Interleukin (IL) -2 and/or IL-15 embedded in the matrix enhanced T cell survival and further promoted T cell migration. The interleukin-13 receptor alpha 2 specific (IL-13R alpha2) T cells that traveled out of the fibrin clot retained the capacity to kill U251 glioma cells. In summary, CTLs can survive and migrate robustly in fibrin matrices. These processes can be influenced by modification of matrix constituents. We conclude that fibrin matrices may be suitable T cell carriers and can be used to facilitate understanding of T cell interaction with the surrounding microenvironment. PMID:22496835
Cytotoxic T lymphocyte trafficking and survival in an augmented fibrin matrix carrier.
Zou, Zhaoxia; Denny, Erin; Brown, Christine E; Jensen, Michael C; Li, Gang; Fujii, Tatsuhiro; Neman, Josh; Jandial, Rahul; Chen, Mike
2012-01-01
Cell-based therapies have intriguing potential for the treatment of a variety of neurological disorders. One such example is genetically engineered cytotoxic T lymphocytes (CTLs) that are being investigated in brain tumor clinical trials. The development of methods for CTL delivery is critical to their use in the laboratory and clinical setting. In our study, we determined whether CTLs can migrate through fibrin matrices and if their migration, survival, and function could be modulated by adding chemokines to the matrix. Our results indicated that CTLs can freely migrate through fibrin matrices. As expected, the addition of the monocyte chemotactic protein-1 (MCP-1), also known as chemokine C-C motif ligand 2 (CCL2), to the surrounding media increased egress of the CTLs out of the fibrin clot. Interleukin (IL) -2 and/or IL-15 embedded in the matrix enhanced T cell survival and further promoted T cell migration. The interleukin-13 receptor alpha 2 specific (IL-13R alpha2) T cells that traveled out of the fibrin clot retained the capacity to kill U251 glioma cells. In summary, CTLs can survive and migrate robustly in fibrin matrices. These processes can be influenced by modification of matrix constituents. We conclude that fibrin matrices may be suitable T cell carriers and can be used to facilitate understanding of T cell interaction with the surrounding microenvironment.
Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.
Sharma, Vaibhav; Kohli, Nupur; Moulding, Dale; Afolabi, Halimat; Hook, Lilian; Mason, Chris; García-Gareta, Elena
2017-11-01
The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection
Orci, Lorenzo A; Oldani, Graziano; Berney, Thierry; Andres, Axel; Mentha, Gilles; Morel, Philippe; Toso, Christian
2014-01-01
Introduction Post-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery. Methods A comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration. Results Seven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6–1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18–1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25–1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay. Conclusion On the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection. PMID:23461684
Onouchi, Takanori; Shiogama, Kazuya; Mizutani, Yasuyoshi; Takaki, Takashi; Tsutsumi, Yutaka
2016-01-01
Neutrophil extracellular traps (NETs) released from dead neutrophils at the site of inflammation represent webs of neutrophilic DNA stretches dotted with granule-derived antimicrobial proteins, including lactoferrin, and play important roles in innate immunity against microbial infection. We have shown the coexistence of NETs and fibrin meshwork in varied fibrinopurulent inflammatory lesions at both light and electron microscopic levels. In the present study, correlative light and electron microscopy (CLEM) employing confocal laser scanning microscopy and scanning electron microscopy was performed to bridge light and electron microscopic images of NETs and fibrin fibrils in formalin-fixed, paraffin-embedded, autopsied lung sections of legionnaire’s pneumonia. Lactoferrin immunoreactivity and 4'-6-diamidino-2-phenylindole (DAPI) reactivity were used as markers of NETs, and fibrin was probed by fibrinogen gamma chain. Of note is that NETs light microscopically represented as lactoferrin and DAPI-colocalized dots, 2.5 μm in diameter. CLEM gave super-resolution images of NETs and fibrin fibrils: “Dotted” NETs were ultrastructurally composed of fine filaments and masses of 58 nm-sized globular materials. A fibrin fibril consisted of clusters of smooth-surfaced filaments. NETs filaments (26 nm in diameter) were significantly thinner than fibrin filaments (295 nm in diameter). Of note is that CLEM was applicable to formalin-fixed, paraffin-embedded sections of autopsy material. PMID:27917008
Kao, K C; Tsai, Y H; Lin, M C; Huang, C C; Tsao, C Y; Chen, Y C
2000-01-01
A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.
Rapid fibrin plug formation within cutaneous ablative fractional CO2 laser lesions.
Kositratna, Garuna; Evers, Michael; Sajjadi, Amir; Manstein, Dieter
2016-02-01
Ablative fractional laser procedures have been shown to facilitate topical drug delivery into the skin. Past studies have mainly used ex vivo models to demonstrate enhanced drug delivery and in vivo studies have investigated laser created channels over a time course of days and weeks rather than within the first few minutes and hours after exposures. We have noticed rapid in vivo fibrin plug formation within ablative fractional laser lesions impairing passage through the laser created channels. In vivo laser exposures were performed in a porcine model. A fractional CO2 laser (AcuPulse™ system, AcuScan 120™ handpiece, Lumenis, Inc., Yokneam, Israel) was programmed in quasi-continuous wave (QCW) mode, at 40W, 50 mJ per pulse, 5% coverage, nominal 120 µm spot size, 8 × 8 mm square pattern, 169 MTZs per scan. Six millimeters punch biopsies were procured at 0, 2, 5, 10, 15, 30, 60, 90 minutes after completion of each scan, then fixed in 10% formalin. 12 repeats were performed of each time point. Skin samples were processed for serial vertically cut paraffin sections (5 μm collected every 25 μm) then H&E and special immunohistochemistry staining for fibrin and platelet. Dimensions of Microscopic Treatment Zones (MTZs) and extent of fibrin plug were assessed and quantified histologically. Ex vivo laser exposures of the identical laser parameter were performed on porcine and human skin at different storage conditions. Histology procured at various predetermined time intervals after in vivo fractional CO2 laser exposures revealed a rapidly forming fibrin plug initiating at the bottom of the MTZ lesions. At longer time intervals, the fibrin plug was extending towards the superficial sections. Within the first 5 minutes, more than 25% length of the entire laser-ablated channel was filled with a fibrin plug. With increased time intervals, the cavity was progressively filled with a fibrin plug. At 90 minutes, more than 90% length of the entire laser-ablated channel was occluded. Ex vivo exposures failed to produce any significant fibrin plug formation. The current study has demonstrated rapid fibrin plug formation after ablative fractional laser procedures. It was shown that the passage through laser created pathways is critically time dependent for in vivo exposures. In contrast, ex vivo exposures do not exhibit such time dependent passage capacity. In particular, drug, substance, and cell delivery studies for ablative fractional laser treatments should take early fibrin plug formation into consideration and further investigate the impact on transdermal delivery. © 2015 Wiley Periodicals, Inc.
Composition Formulas of Inorganic Compounds in Terms of Cluster Plus Glue Atom Model.
Ma, Yanping; Dong, Dandan; Wu, Aimin; Dong, Chuang
2018-01-16
The present paper attempts to identify the molecule-like structural units in inorganic compounds, by applying the so-called "cluster plus glue atom model". This model, originating from metallic glasses and quasi-crystals, describes any structure in terms of a nearest-neighbor cluster and a few outer-shell glue atoms, expressed in the cluster formula [cluster](glue atoms). Similar to the case for normal molecules where the charge transfer occurs within the molecule to meet the commonly known octet electron rule, the octet state is reached after matching the nearest-neighbor cluster with certain outer-shell glue atoms. These kinds of structural units contain information on local atomic configuration, chemical composition, and electron numbers, just as for normal molecules. It is shown that the formulas of typical inorganic compounds, such as fluorides, oxides, and nitrides, satisfy a similar octet electron rule, with the total number of valence electrons per unit formula being multiples of eight.
Hodde, Dorothee; Gerardo-Nava, José; Wöhlk, Vanessa; Weinandy, Stefan; Jockenhövel, Stefan; Kriebel, Andreas; Altinova, Haktan; Steinbusch, Harry W M; Möller, Martin; Weis, Joachim; Mey, Jörg; Brook, Gary A
2016-02-01
The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell-substrate interactions between purified populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two-dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre-containing fibrin hydrogel reached near-maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three-dimensional, extracellular matrix-mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Compression-induced structural and mechanical changes of fibrin-collagen composites.
Kim, O V; Litvinov, R I; Chen, J; Chen, D Z; Weisel, J W; Alber, M S
2017-07-01
Fibrin and collagen as well as their combinations play an important biological role in tissue regeneration and are widely employed in surgery as fleeces or sealants and in bioengineering as tissue scaffolds. Earlier studies demonstrated that fibrin-collagen composite networks displayed improved tensile mechanical properties compared to the isolated protein matrices. Unlike previous studies, here unconfined compression was applied to a fibrin-collagen filamentous polymer composite matrix to study its structural and mechanical responses to compressive deformation. Combining collagen with fibrin resulted in formation of a composite hydrogel exhibiting synergistic mechanical properties compared to the isolated fibrin and collagen matrices. Specifically, the composite matrix revealed a one order of magnitude increase in the shear storage modulus at compressive strains>0.8 in response to compression compared to the mechanical features of individual components. These material enhancements were attributed to the observed structural alterations, such as network density changes, an increase in connectivity along with criss-crossing, and bundling of fibers. In addition, the compressed composite collagen/fibrin networks revealed a non-linear transformation of their viscoelastic properties with softening and stiffening regimes. These transitions were shown to depend on protein concentrations. Namely, a decrease in protein content drastically affected the mechanical response of the networks to compression by shifting the onset of stiffening to higher degrees of compression. Since both natural and artificially composed extracellular matrices experience compression in various (patho)physiological conditions, our results provide new insights into the structural biomechanics of the polymeric composite matrix that can help to create fibrin-collagen sealants, sponges, and tissue scaffolds with tunable and predictable mechanical properties. Copyright © 2016 Elsevier B.V. All rights reserved.
Zhu, Shu; Diamond, Scott L
2014-12-01
Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s(-1)), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s(-1) (compared to fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.
Pan, Xiaoxi; Gong, Yun Yun; Martinelli, Ida; Angelici, Laura; Favero, Chiara; Bertazzi, Pier Alberto; Mannucci, Pier M; Ariëns, Robert A S; Routledge, Michael N
2016-01-01
Particulate air pollution is a risk factor for cardiovascular diseases and thrombosis. Long-term exposure to particulate matter with a diameter<10μm (PM10) has been associated with an increased risk of venous thrombosis. The aim of this study was to investigate whether or not particulate air pollution alters fibrin clot structure and thus modulates thrombosis risk. We investigated fibrin polymerization by turbidity (maximum absorbance mOD), clot structure by confocal microscopy (fibre number per μm) and fibrin pore size by permeability (Ks×10(-10)cm(2)) in 103 patients with deep vein thrombosis and 121 healthy controls, for whom levels of air pollution exposure had been recorded. Exposure groups were defined by mean PM10 concentrations over the 730days before the event. We found a higher average number of fibres per clot area in patients than controls, but no difference in Ks or fibre thickness. When the two groups were divided into high or low exposure to PM10, a significantly denser fibrin clot network structure with thicker fibres (higher maximum absorbance, p<0.05), decreased permeability (lower Ks value, p<0.05) and higher average fibre numbers per clot area (p<0.05) was observed in patients in the high exposure group compared to those with low exposure. There were no significant differences in fibrin clot structure between the two exposure levels in healthy subjects. PM10 levels are associated with altered fibrin clot structure in patients with deep vein thrombosis but not in controls, suggesting that air pollution may trigger differences in fibrin clot structure only in patients predisposed to thrombotic disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
A safe and efficient method to retrieve mesenchymal stem cells from three-dimensional fibrin gels.
Carrion, Bita; Janson, Isaac A; Kong, Yen P; Putnam, Andrew J
2014-03-01
Mesenchymal stem cells (MSCs) display multipotent characteristics that make them ideal for potential therapeutic applications. MSCs are typically cultured as monolayers on tissue culture plastic, but there is increasing evidence suggesting that they may lose their multipotency over time in vitro and eventually cease to retain any resemblance to in vivo resident MSCs. Three-dimensional (3D) culture systems that more closely recapitulate the physiological environment of MSCs and other cell types are increasingly explored for their capacity to support and maintain the cell phenotypes. In much of our own work, we have utilized fibrin, a natural protein-based material that serves as the provisional extracellular matrix during wound healing. Fibrin has proven to be useful in numerous tissue engineering applications and has been used clinically as a hemostatic material. Its rapid self-assembly driven by thrombin-mediated alteration of fibrinogen makes fibrin an attractive 3D substrate, in which cells can adhere, spread, proliferate, and undergo complex morphogenetic programs. However, there is a significant need for simple cost-effective methods to safely retrieve cells encapsulated within fibrin hydrogels to perform additional analyses or use the cells for therapy. Here, we present a safe and efficient protocol for the isolation of MSCs from 3D fibrin gels. The key ingredient of our successful extraction method is nattokinase, a serine protease of the subtilisin family that has a strong fibrinolytic activity. Our data show that MSCs recovered from 3D fibrin gels using nattokinase are not only viable but also retain their proliferative and multilineage potentials. Demonstrated for MSCs, this method can be readily adapted to retrieve any other cell type from 3D fibrin gel constructs for various applications, including expansion, bioassays, and in vivo implantation.
A Safe and Efficient Method to Retrieve Mesenchymal Stem Cells from Three-Dimensional Fibrin Gels
Carrion, Bita; Janson, Isaac A.; Kong, Yen P.
2014-01-01
Mesenchymal stem cells (MSCs) display multipotent characteristics that make them ideal for potential therapeutic applications. MSCs are typically cultured as monolayers on tissue culture plastic, but there is increasing evidence suggesting that they may lose their multipotency over time in vitro and eventually cease to retain any resemblance to in vivo resident MSCs. Three-dimensional (3D) culture systems that more closely recapitulate the physiological environment of MSCs and other cell types are increasingly explored for their capacity to support and maintain the cell phenotypes. In much of our own work, we have utilized fibrin, a natural protein-based material that serves as the provisional extracellular matrix during wound healing. Fibrin has proven to be useful in numerous tissue engineering applications and has been used clinically as a hemostatic material. Its rapid self-assembly driven by thrombin-mediated alteration of fibrinogen makes fibrin an attractive 3D substrate, in which cells can adhere, spread, proliferate, and undergo complex morphogenetic programs. However, there is a significant need for simple cost-effective methods to safely retrieve cells encapsulated within fibrin hydrogels to perform additional analyses or use the cells for therapy. Here, we present a safe and efficient protocol for the isolation of MSCs from 3D fibrin gels. The key ingredient of our successful extraction method is nattokinase, a serine protease of the subtilisin family that has a strong fibrinolytic activity. Our data show that MSCs recovered from 3D fibrin gels using nattokinase are not only viable but also retain their proliferative and multilineage potentials. Demonstrated for MSCs, this method can be readily adapted to retrieve any other cell type from 3D fibrin gel constructs for various applications, including expansion, bioassays, and in vivo implantation. PMID:23808842
Lucas, Thabata Coaglio; Tessarolo, Francesco; Jakitsch, Victor; Caola, Iole; Brunori, Giuliano; Nollo, Giandomenico; Huebner, Rudolf
2014-07-01
Although catheters with side holes allow high flow rate during hemodialysis, they also induce flow disturbances and create a critical hemodynamic environment that can favor fibrin deposition and thrombus formation. This study compared the blood flow and analyzed the influence of shear stress and shear rate in fibrin deposition and thrombus formation in nontunneled hemodialysis catheters with unobstructed side holes (unobstructed device) or with some side holes obstructed by blood thrombi (obstructed device). Computational fluid dynamics (CFD) was performed to simulate realistic blood flow under laminar and turbulent conditions. The results from the numerical simulations were compared with the fibrin distribution and thrombus architecture data obtained from scanning electron microscopy (SEM) and two photons laser scanning microscopy (TPLSM) on human thrombus formed in catheters removed from patients. CFD showed that regions of flow eddies and separation were mainly found in the venous holes region. TPLSM characterization of thrombi and fibrin structure in patient samples showed fibrin formations in accordance with simulated flux dynamics. Under laminar flow conditions, the wall shear stress close to border holes increased from 87.3±0.2 Pa in the unobstructed device to 176.2±0.5 Pa in the obstructed one. Under turbulent flow conditions, the shear stress increased by 47% when comparing the obstructed to the unobstructed catheter. The shear rates were generally higher than 5000/s and therefore sufficient to induce fibrin deposition. This findings were supported by SEM data documenting a preferential fibrin arrangement on side hole walls. Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Prospective randomized controlled trial: fibrin sealant reduces split skin graft donor-site pain.
Healy, Ciaran; Greig, Aina V H; Murphy, Adrian D; Powell, Christopher; Pinder, Richard J; Saour, Samer; Abela, Christopher; Knight, William; Geh, Jenny L C
2013-07-01
Pain at split skin graft donor sites is common. Fibrin sealant has been demonstrated to reduce time to hemostasis at wound sites, and patients receiving this treatment were incidentally noted to report less pain. This study aimed to evaluate pain and incapacity in split skin graft donor sites treated with and without fibrin sealant. Fifty patients requiring thigh donor-site split skin grafts were prospectively randomized to receive either a self-adhesive fabric dressing alone or fibrin sealant plus the self-adhesive fabric dressing as primary donor-site dressings. External secondary dressings were the same. Patients were blinded with regard to treatment group. Using visual analogue scales (scored 0 to 5), patients rated their donor-site pain and incapacity for 14 days postoperatively. Secondary endpoints were length of hospital stay and duration of requirement for dressings. Forty patients were included in the study analysis and completed self-reported pain and incapacity scores. Twenty received the fibrin sealant plus self-adhesive fabric dressing and 20 received the fabric dressing only (controls). Patients using the fibrin sealant plus the dressing reported significantly less pain (mean score, 0.42 versus 1.60, p < 0.001) and significantly less incapacity (mean score, 0.48 versus 1.71, p < 0.001). Patients allocated to the fibrin sealant group recorded shorter lengths of stay and faster time to discontinuation of dressing, though statistical significance was not achieved. Patients whose split skin graft donor sites were dressed with fibrin sealant plus self-adhesive fabric dressing experienced significantly less pain and incapacity than patients with self-adhesive fabric dressings alone, allowing a more rapid return to normal activity. Therapeutic, II.
Kumar, Kalainesan Rajesh; Vennila, Rathinam; Kanchana, Shankar; Arumugam, Muthuvel; Balasubramaniam, Thangavel
2011-05-01
Stingray envenomation is one of the major problems in the marine and freshwater ecosystem. Accidents in human cause immediate, local and intense pain, erythema, edema, hemorrhage, tissue necrosis and secondary bacterial infection are also common. To determine the effect of two marine stingray species Dasyatis sephen and Aetobatis narinari venom extract on coagulation, fibrin(ogen)olytic, proteolytic activities. Plasma coagulation, Thrombin catalyzed fibrinocoagulation, Fibrin plate assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), substrate SDS-PAGE and thrombin like activity by using chromogenic substrate were used to determine the effect of venom on plasma coagulation, its fibrin(ogen)olytic and proteolytic activity. The results show the presence of fibrin(ogen)olytic, anticoagulant and gelatinolytic activity in both stingray venom extracts. D. sephen venom delays coagulation of citrated plasma more significantly than A. narinari upon using increasing concentration of the venom. The same results were obtained in the fibrinocoagulation assays. SDS-PAGE analysis of fibrinogen and fibrin after incubation with D. sephen and A. narinari venom show fibrin(ogen)olytic activity. Through SDS-PAGE analysis it is confirmed that the delaying in coagulation process by stingray venom is due to its fibrin(ogen)olytic activity and fibrinolytic activity also confirmed through fibrin plate assay. Zymogram analysis shows the presence of array of gelatinolytic and fibrinogenolytic enzymes above 43-276 kDa in the D. sephen and A. narinari venom respectively. Protease inhibitor studies show the serine and metallo proteases are responsible for these activities. From the results, fibrinogenolytic, proteolytic activity of the stingray venom is confirmed, but it has no thrombin like activity and these activities may aid in hemorrhages, tissue necrosis and secondary bacterial infections at the site of envenomation.
Nabiullina, R M; Mustafin, I G; Ataullakhanov, F I; Litvinov, R I; Zubairova, L D
2015-07-01
The effects of blood microparticles (MPs) on the dynamics of fibrin polymerization, clot structure and susceptibility to fibrinolysis were studied. Kinetics of fibrin polymerization, fibrinolysis, thrombin generation in platelet-free, microparticle-depleted and microparticle-depleted plasma replenished with cephalin, from healthy donors were analyzed in parallel. MPs have profound effects on all stages of fibrin formation, decrease its turbidity. All parameters obtained in the absence of MPs were recovered after reconstitution of phospholipids. Thrombin generation rates were reduced in the absence of MPs. In the presence of MPs the fibrin networks had less poro us structures with thinner fibers, while clots formed in the absence of MPs had larger pores and were built of thicker fibers. Clots formed in the presence of MPs were significantly more resistant to fibrinolysis. Results show that normally circulating MPs can support the formation of stable clots at the sites of vascular injury.
Samal, Juhi; Weinandy, Stefan; Weinandy, Agnieszka; Helmedag, Marius; Rongen, Lisanne; Hermanns-Sachweh, Benita; Kundu, Subhas C; Jockenhoevel, Stefan
2015-10-01
A successful strategy to enhance the in vivo survival of engineered tissues would be to prevascularize them. In this study, fabricated silk fibroin scaffolds from mulberry and non-mulberry silkworms are investigated and compared for supporting the co-culture of human umbilical vein endothelial cells and human foreskin fibroblasts. Scaffolds are cytocompatible and when combined with fibrin gel support capillary-like structure formation. Density and interconnectivity of the formed structures are found to be better in mulberry scaffolds. ELISA shows that levels of vascular endothelial growth factor (VEGF) released in co-cultures with fibrin gel are significantly higher than in co-cultures without fibrin gel. RT PCR shows an increase in VEGFR2 expression in mulberry scaffolds indicating these scaffolds combined with fibrin provide a suitable microenvironment for the development of capillary-like structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hedrich, Hans Christian; Simunek, Manuela; Reisinger, Sonja; Ferguson, James; Gulle, Heinz; Goppelt, Andreas; Redl, Heinz
2012-08-01
In this study, we compared the sealing characteristics and efficacy of a fibrin sealant with reduced plasminogen (FS-rplg) and a fibrin sealant with aprotinin as a fibrinolysis inhibitor (FS-apr). The relevant sealing characteristics including clot structure, fibrin chain cross-linking, and clot lysis were tested in the laboratory. The sealing efficacy was then investigated in a follow-up animal model to determine differences in the in vivo sealing properties. A total of 46 animals were available for the final analysis with 23 animals in each treatment arm. In conclusion, we saw differences in vitro between FS-rplg and FS-apr in ultrastructure and α-chain cross-linking rates as well as in the rate of fibrinolysis. These differences may explain the significantly enhanced sealing efficacy in FS-apr compared to FS-rplg shown in vivo in a rabbit intestinal model. Copyright © 2012 Wiley Periodicals, Inc.
[Emission of organic substances from chip-boards].
Deppe, H J
1982-01-01
A relatively small number of investigations on emissions of organic substances from chip-board is available up to now. The emissions known to date are caused by glues or other additives rather than by the wood itself. As concerns aminoplast glues (urea-formaldehyde or melamine-formaldehyde resins) the most important point of public interest has been the off-gassing of formaldehyde from chip-board. Chip-board with phenol-formaldehyde glues has been known in some cases to give off phenol. The formation of diamino diphenyl methane from isocyanate glues is still a matter of discussion. A further source for possible emissions are wood and fire protectives which are added during the manufacturing process. Finally, coating of chip-board may lead to emissions of organic substances. The lack of adequate detection methods has so far delayed the treatment of questions in relation to emissions from chip-board. Even now, there are numerous problems in this field especially when investigating isocyanate glues. Problems in relation to the origin of emissions due to the kind of glue used and the manufacturing process are discussed, and proposals are made how to solve some of these problems. The question of the health risk is dealt with from the view-point of the civil engineer and in an general economic context.
Zhou, Yujia; Wang, Gesheng; Liu, Jialin; Du, Yong; Wang, Lei; Wang, Xiaoyong
2016-01-01
Background The aim of this study was to evaluate the application of medical adhesive glue for tension-reduced duraplasty in decompressive craniotomy. Material/Methods A total of 56 cases were enrolled for this study from Jan 2013 to May 2015. All patients underwent decompressive craniotomy and the dura was repaired in all of them with tension-reduced duraplasty using the COMPONT medical adhesive to glue artificial dura together. The postoperative complications and the healing of dura mater were observed and recorded. Results No wound infection, epidural or subdural hematoma, cerebrospinal fluid leakage, or other complications associated with the procedure occurred, and there were no allergic reactions to the COMPONT medical adhesive glue. The second-phase surgery of cranioplasty was performed at 3 to 6 months after the decompressive craniotomy in 32 out of the 56 cases. During the cranioplasty we observed no adherence of the artificial dura mater patch to the skin flap, no residual COMPONT glue, or hydropic or contracture change of tissue at the surgical sites. Additionally, no defect or weakening of the adherence between the artificial dura mater patch and the self dura matter occurred. Conclusions COMPONT medical adhesive glue is a safe and reliable tool for tension-reduced duraplasty in decompressive craniotomy. PMID:27752035
Mogaki, Rina
2015-01-01
Water-soluble bioadhesive polymers bearing multiple guanidinium ion (Gu+) pendants at their side-chain termini (Gluen–BA, n = 10 and 29) that were conjugated with benzamidine (BA) as a trypsin inhibitor were developed. The Gluen–BA molecules are supposed to adhere to oxyanionic regions of the trypsin surface, even in buffer, via a multivalent Gu+/oxyanion salt-bridge interaction, such that their BA group properly blocks the substrate-binding site. In fact, Glue10–BA and Glue29–BA exhibited 35- and 200-fold higher affinities for trypsin, respectively, than a BA derivative without the glue moiety (TEG–BA). Most importantly, Glue10–BA inhibited the protease activity of trypsin 13-fold more than TEG–BA. In sharp contrast, mGlue27–BA, which bears 27 Gu+ units along the main chain and has a 5-fold higher affinity than TEG–BA for trypsin, was inferior even to TEG–BA for trypsin inhibition. PMID:28706668
Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.
Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed
2016-05-01
Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. Copyright © 2016 Elsevier Inc. All rights reserved.
Ortillés, Á; Pascual, G; Peña, E; Rodríguez, M; Pérez-Köhler, B; Mesa-Ciller, C; Calvo, B; Bellón, J M
2017-11-01
The use of an adhesive for mesh fixation in hernia repair reduces chronic pain and minimizes tissue damage in the patient. This study was designed to assess the adhesive properties of a medium-chain (n-butyl) cyanoacrylate glue applied as drops or as a spray in a biomechanical and histologic study. Both forms of glue application were compared to the use of simple-loose or continuous-running polypropylene sutures for mesh fixation. Eighteen adult New Zealand White rabbits were used. For mechanical tests in an ex vivo and in vivo study, patches of polypropylene mesh were fixed to an excised fragment of healthy abdominal tissue or used to repair a partial abdominal wall defect in the rabbit respectively. Depending on the fixation method used, four groups of 12 implants each or 10 implants each respectively for the ex vivo and in vivo studies were established: Glue-Drops, Glue-Spray, Suture-Simple and Suture-Continuous. Biomechanical resistance in the ex vivo implants was tested five minutes after mesh fixation. In vivo implants for biomechanical and histologic assessment were collected at 14 days postimplant. In the ex vivo study, the continuous suture implants showed the highest failure sample tension, while the implants fixed with glue showed lower failure sample tension values. However, the simple and continuous suture implants returned the highest stretch values. In the in vivo implants, failure sample tension values were similar among groups while the implants fixed with a continuous running suture had the higher stretch values, and the glue-fixed implants the lower stretch values. All meshes showed good tissue integration within the host tissue regardless of the fixation method used. Our histologic study revealed the generation of a denser, more mature repair tissue when the cyanoacrylate glue was applied as a spray rather than as drops. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Technical Reports Server (NTRS)
Matskevichene, V. B.; Platonova, A. T.
1974-01-01
The effect of a constant magnetic field with a strength of 2500 oersteds on the fibrinogen-fibrin system was studied in the organism of healthy rabbits with exposure times of 1 and 5 hours. The results obtained indicate disruptions in the stage of conversion of fibrinogen to fibrin and an increase in the amount of fibrinogen.
Integrating-Sphere Measurements for Determining Optical Properties of Tissue-Engineered Oral Mucosa
NASA Astrophysics Data System (ADS)
Ionescu, A. M.; Cardona, J. C.; Garzón, I.; Oliveira, A. C.; Ghinea, R.; Alaminos, M.; Pérez, M. M.
2015-02-01
Surgical procedures carried out in the oral and maxillofacial region can result in large tissue defects. Accounting for the shortage of oral mucosa to replace the excised tissues, different models of an organotypic substitute of the oral mucosa generated by tissue engineering have recently been proposed. In this work, the propagation of light radiation through artificial human oral mucosa substitutes based on fibrin-agarose scaffolds (fibrin, fibrin-0.1% agarose, fibrin-0.2%agarose) is investigated, and their optical properties are determined using the inverse adding-doubling (IAD) method based on integrating-sphere measurements. Similar values for the absorption and scattering coefficients between the fibrin and fibrin-0.1% agarose bioengineered tissues and the native oral mucosa were found. These results suggest the adequacy of these biomaterials for potential clinical use in human oral mucosa applications. These optical properties represent useful references and data for applications requiring the knowledge of the light transport through this type of tissues, applications used in clinical practice. It also provides a new method of information analysis for the quality control of the development of the artificial nanostructured oral mucosa substitutes and its comparison with native oral mucosa tissues.
Fibrin Association at Hybrid Biointerfaces Made of Clot-Binding Peptides and Polythiophene.
Puiggalí-Jou, A; Del Valle, Luis J; Armelin, Elaine; Alemán, Carlos
2016-10-01
The properties as biointerfaces of electroactive conducting polymer-peptide biocomposites formed by poly(3,4-ethylenedioxythiophene) (PEDOT) and CREKA or CR(NMe)EKA peptide sequences (where Glu has been replaced by N-methyl-Glu in the latter) have been compared. CREKA is a linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, while CR(NMe)EKA is an engineer to improve such properties by altering peptide-fibrin interactions. Differences between PEDOT-CREKA and PEDOT-CR(NMe)EKA reflect dissemblance in the organization of the peptides into the polymeric matrix. Both peptides affect fibrinogen thrombin-catalyzed polymerization causing the immediate formation of fibrin, whereas in the absence of thrombin this phenomenon is only observed for CR(NMe)EKA. Consistently, the fibrin-adsorption capacity is higher for PEDOT-CR(NMe)EKA than for PEDOT-CREKA, even though in both cases adsorbed fibrin exhibits round-like morphologies rather than the characteristic fibrous structure. PEDOT-peptide films coated with fibrin are selective in terms of cell adhesion, promoting the attachment of metastatic cells with respect to normal cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Onouchi, Takanori; Shiogama, Kazuya; Matsui, Takahiro; Mizutani, Yasuyoshi; Sakurai, Kouhei; Inada, Ken-ichi; Tsutsumi, Yutaka
2016-01-01
Neutrophil extracellular traps (NETs) represent an extracellular, spider’s web-like structure resulting from cell death of neutrophils. NETs play an important role in innate immunity against microbial infection, but their roles in human pathological processes remain largely unknown. NETs and fibrin meshwork both showing fibrillar structures are observed at the site of fibrinopurulent inflammation, as described in our sister paper [Acta Histochem. Cytochem. 49; 109–116, 2016]. In the present study, immunoelectron microscopic study was performed for visualizing NETs and fibrin fibrils (thick fibrils in our tongue) in formalin-fixed, paraffin-embedded sections of autopsied lung tissue of legionnaire’s pneumonia. Lactoferrin and fibrinogen gamma chain were utilized as markers of NETs and fibrin, respectively. Analysis of immuno-scanning electron microscopy indicated that NETs constructed thin fibrils and granular materials were attached onto the NETs fibrils. The smooth-surfaced fibrin fibrils were much thicker than the NETs fibrils. Pre-embedding immunoelectron microscopy demonstrated that lactoferrin immunoreactivities were visible as dots on the fibrils, whereas fibrinogen gamma chain immunoreactivities were homogeneously observed throughout the fibrils. Usefulness of immunoelectron microscopic analysis of NETs and fibrin fibrils should be emphasized. PMID:27682015
Bromberek, B A; Enever, P A J; Shreiber, D I; Caldwell, M D; Tranquillo, R T
2002-05-01
Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin gel sphere, while the inner core either was devoid of cells or contained peritoneal exudate cells (primarily macrophages), thereby mimicking the inflammatory phase of wound healing. The fibroblasts compacted floating fibrin microspheres over time. In the absence of macrophages, the initial distribution of fibroblasts (only in the shell) induced circumferential alignment of fibrin fibrils via compaction of the shell relative to the core. The aligned fibrils created a contact guidance field, which was manifested by strong circumferential alignment of the fibroblasts. However, in the presence of macrophages, the fibroblasts exhibited more radial alignment despite the simultaneous contact guidance field in the circumferential direction associated with compaction. This was attributed to a chemotactic gradient emanating from the core due to a putative factor(s) released by the macrophages. The presence of a radial chemotactic stimulus was supported by the finding of even greater radial alignment when fibrin microspheres were embedded in an agarose-fibrin gel that abolished compaction and consequently the contact guidance field. Our assay permits the simulation of tissue morphogenetic processes that involve cell guidance phenomena and tractional restructuring of the extracellular matrix.
Vardar, E; Larsson, H M; Allazetta, S; Engelhardt, E M; Pinnagoda, K; Vythilingam, G; Hubbell, J A; Lutolf, M P; Frey, P
2018-02-01
Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 μm and recombinant fibrin-binding insulin-like growth factor-1 (α 2 PI 1-8 -MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α 2 PI 1-8 -MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences. Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α 2 PI 1-8 -MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Measurement of radiation damage on an epoxy-based optical glue
NASA Astrophysics Data System (ADS)
Huang, H. C.; Peng, K. C.; Sahu, S. K.; Ueno, K.; Chang, Y. H.; Wang, C. H.; Hou, W. S.
1997-02-01
We measured the radiation damage on an optical glue called Eccobond-24, which is a candidate for CsI and BGO crystal calorimeters of the BELLE detector of the KEK B-factory. Absorption spectrophotometry in the range 300-800 nm was used to monitor the radiation damage. The maximum equivalent dose was 1.64 Mrad. The glue shows effects of damage, but is acceptable for the radiation level in the above-mentioned experiment.
Therapeutic ureteral occlusion with Ifabond cyanoacrylate glue: an interesting solution.
Oderda, Marco; Lacquaniti, Sergio; Fraire, Flavio; Antolini, Jacopo; Camilli, Marco; Mandras, Roberto; Puccetti, Luca; Varvello, Francesco; Fasolis, Giuseppe
2017-08-01
The aim of this study was to present a novel approach for complete and permanent ureteral occlusion using a percutaneous injection of Ifabond cyanoacrylate glue. We describe in detail all the steps of our surgery, performed on a 79-year-old patient with urinary leakage from ureteral stump following radical cystectomy. N-hexyl-cyanoacrylate glue (Ifabond) was used to occlude the distal ureter and solve the leakage. Our approach was successful, sparing our already frail patient further surgical procedures. Six months pyelography confirmed the complete ureteral blockage with absence of extravasation. In complicated scenarios with urinary leakages and frail patients, synthetic glues such as Ifabond might represent an interesting therapeutic option to solve the fistulas, leading to durable success with a minimally invasive approach.
Stevens, J.; Barbosa, F.; Bessuille, J.; ...
2016-07-20
Here, the GlueX experiment was designed to search for and study the pattern of gluonic excitations in the meson spectrum produced through photoproduction reactions at a new tagged photon beam facility in Hall D at Jefferson Laboratory. The particle identification capabilities of the GlueX experiment will be enhanced by constructing a DIRC (Detection of Internally Reflected Cherenkov light) detector, utilizing components of the decommissioned BaBar DIRC. The DIRC will allow systematic studies of kaon final states that are essential for inferring the quark flavor content of both hybrid and conventional mesons. In this contribution, the design for the GlueX DIRCmore » will be discussed including new expansion volumes, read out with MaPMTs, that are currently under development.« less
Kurniawan, Nicholas A; Vos, Bart E; Biebricher, Andreas; Wuite, Gijs J L; Peterman, Erwin J G; Koenderink, Gijsje H
2016-09-06
Tissues and cells sustain recurring mechanical loads that span a wide range of loading amplitudes and timescales as a consequence of exposure to blood flow, muscle activity, and external impact. Both tissues and cells derive their mechanical strength from fibrous protein scaffolds, which typically have a complex hierarchical structure. In this study, we focus on a prototypical hierarchical biomaterial, fibrin, which is one of the most resilient naturally occurring biopolymers and forms the structural scaffold of blood clots. We show how fibrous networks composed of fibrin utilize irreversible changes in their hierarchical structure at different scales to maintain reversible stress stiffening up to large strains. To trace the origin of this paradoxical resilience, we systematically tuned the microstructural parameters of fibrin and used a combination of optical tweezers and fluorescence microscopy to measure the interactions of single fibrin fibers for the first time, to our knowledge. We demonstrate that fibrin networks adapt to moderate strains by remodeling at the network scale through the spontaneous formation of new bonds between fibers, whereas they adapt to high strains by plastic remodeling of the fibers themselves. This multiscale adaptation mechanism endows fibrin gels with the remarkable ability to sustain recurring loads due to shear flows and wound stretching. Our findings therefore reveal a microscopic mechanism by which tissues and cells can balance elastic nonlinearity and plasticity, and thus can provide microstructural insights into cell-driven remodeling of tissues. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Sanjay, Pandanaboyana; Watt, David G; Wigmore, Stephen J
2013-04-01
Fibrin sealants are frequently used in liver surgery to achieve intraoperative haemostasis and reduce post-operative haemorrhage and bile leak. This meta-analysis aimed to review the haemostatic and biliostatic capacity of fibrin sealants in elective liver surgery. An electronic search was performed on the MEDLINE, Embase and PubMed databases using both subject headings and truncated word searches to identify all published articles that are related to this topic. Pooled risk ratios were calculated for categorical outcomes, and mean differences for secondary continuous outcomes, using the fixed-effects and random-effects models for meta-analysis. Ten randomised controlled trials encompassing 1,225 patients were analysed to achieve a summated outcome. Pooled data analysis showed the use of fibrin sealants resulted in reduced time to haemostasis (mean difference -3.45 min [-3.78, -3.13] (P < 0.00001)) and increased numbers of patients with complete haemostasis (risk ratio 1.56, 95 % confidence interval 1.04-2.34, p = 0.03) when compared to controls. The use of fibrin sealants did not influence perioperative blood transfusion requirements, bile leak rates, post-operative haemorrhage, intra-abdominal collections and overall morbidity and mortality compared with controls. There is no solid evidence that the routine use of fibrin sealants reduces the incidence of post-operative haemorrhage or bile leak compared with other treatments. The use of fibrin sealants may reduce the time to haemostasis, but this does not translate to improved perioperative outcomes.
Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII.
Rijken, D C; Abdul, S; Malfliet, J J M C; Leebeek, F W G; Uitte de Willige, S
2016-07-01
Essentials Factor XIIIa inhibits fibrinolysis by forming fibrin-fibrin and fibrin-inhibitor cross-links. Conflicting studies about magnitude and mechanisms of inhibition have been reported. Factor XIIIa most strongly inhibits lysis of mechanically compacted or retracted plasma clots. Cross-links of α2-antiplasmin to fibrin prevent the inhibitor from being expelled from the clot. Background Although insights into the underlying mechanisms of the effect of factor XIII on fibrinolysis have improved considerably in the last few decades, in particular with the discovery that activated FXIII (FXIIIa) cross-links α2 -antiplasmin to fibrin, the topic remains a matter of debate. Objective To elucidate the mechanisms of the antifibrinolytic effect of FXIII. Methods and Results Platelet-poor plasma clot lysis, induced by the addition of tissue-type plasminogen activator, was measured in the presence or absence of a specific FXIIIa inhibitor. Both in a turbidity assay and in a fluorescence assay, the FXIIIa inhibitor had only a small inhibitory effect: 1.6-fold less tissue-type plasminogen activator was required for 50% clot lysis in the presence of the FXIIIa inhibitor. However, when the plasma clot was compacted by centrifugation, the FXIIIa inhibitor had a strong inhibitory effect, with 7.7-fold less tissue-type plasminogen activator being required for 50% clot lysis in the presence of the FXIIIa inhibitor. In both experiments, the effects of the FXIIIa inhibitor were entirely dependent on the cross-linking of α2 -antiplasmin to fibrin. The FXIIIa inhibitor reduced the amount of α2 -antiplasmin present in the compacted clots from approximately 30% to < 4%. The results were confirmed with experiments in which compaction was achieved by platelet-mediated clot retraction. Conclusions Compaction or retraction of fibrin clots reveals the strong antifibrinolytic effect of FXIII. This is explained by the cross-linking of α2 -antiplasmin to fibrin by FXIIIa, which prevents the plasmin inhibitor from being fully expelled from the clot during compaction/retraction. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
Nakayama, Y; Matsuda, T
1999-01-01
This article presents a novel photochemically driven surgical tissue adhesive technology using photoreactive gelatins and a water-soluble difunctional macromer (poly(ethylene glycol) diacrylate: PEGDA).The gelatins were partially derivatized with photoreactive groups, such as ultraviolet light (UV)-reactive benzophenone and visible light-reactive xanthene dye (e.g., fluorescein sodium salt, eosin Y, and rose bengal). A series of the prepared photocurable tissue adhesive glues, consisting of the photoreactive gelatin, PEGDA, and a saline solution with or without ascorbic acid as a reducing agent, were viscous solutions under warming, and their effectiveness was evaluated as hemostasis- and anastomosis-aid in cardiovascular surgery. Regardless of the type of photoreactive groups, the irradiation of the photocurable tissue adhesive glues by UV or visible light within 1 min produced water-swollen gels, which had a high adhesive strength to wet collagen film. These were due to the synergistic action of photoreactive group-initiated photo-cross-linking and photograft polymerization. An increase in the irradiation time resulted in increased gel yield and reduced water swellability. A decrease in the molecular weight of PEGDA and an increase in concentration of both gelatin and PEGDA resulted in reduced water swellability and increased tensile and burst strengths of the resultant gels. In rats whose livers were injured with a trephine in laparotomy, the bleeding spots were coated with the photocurable adhesive glue and irradiated through an optical fiber. The coated solution was immediately converted to a swollen gel. The gel was tightly adhered to the liver tissue presumably by interpenetration, and concomitantly hemostasis was completed. The anastomosis treatment with the photocurable glue in the canine abdominal or thoracic aortas incised with a knife resulted in little bleeding under pulsatile flow after declamping. Histological examination showed that the glues photocured on rat liver surfaces were gradually degraded with time in vivo with infiltration of inflammatory cells and connective tissues without necrotic sign in surrounding tissue. In addition, in the laparoscopic surgery, percutaneous delivery of the glue and its in situ photogelation on rat liver surfaces were demonstrated using a specially designed fiberscope. These results indicate that the photocurable glues developed here may serve as a biodegradable tissue adhesive glue usable in cardiovascular surgery and endoscopic surgery. Copyright 1999 John Wiley & Sons, Inc.
NASA Astrophysics Data System (ADS)
Shafii, Mahyar; Tolson, Bryan; Shawn Matott, L.
2015-04-01
GLUE is one of the most commonly used informal methodologies for uncertainty estimation in hydrological modelling. Despite the ease-of-use of GLUE, it involves a number of subjective decisions such as the strategy for identifying the behavioural solutions. This study evaluates the impact of behavioural solution identification strategies in GLUE on the quality of model output uncertainty. Moreover, two new strategies are developed to objectively identify behavioural solutions. The first strategy considers Pareto-based ranking of parameter sets, while the second one is based on ranking the parameter sets based on an aggregated criterion. The proposed strategies, as well as the traditional strategies in the literature, are evaluated with respect to reliability (coverage of observations by the envelope of model outcomes) and sharpness (width of the envelope of model outcomes) in different numerical experiments. These experiments include multi-criteria calibration and uncertainty estimation of three rainfall-runoff models with different number of parameters. To demonstrate the importance of behavioural solution identification strategy more appropriately, GLUE is also compared with two other informal multi-criteria calibration and uncertainty estimation methods (Pareto optimization and DDS-AU). The results show that the model output uncertainty varies with the behavioural solution identification strategy, and furthermore, a robust GLUE implementation would require considering multiple behavioural solution identification strategies and choosing the one that generates the desired balance between sharpness and reliability. The proposed objective strategies prove to be the best options in most of the case studies investigated in this research. Implementing such an approach for a high-dimensional calibration problem enables GLUE to generate robust results in comparison with Pareto optimization and DDS-AU.
Calibration of cathode strip gains in multiwire drift chambers of the GlueX experiment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Berdnikov, V. V.; Somov, S. V.; Pentchev, L.
A technique for calibrating cathode strip gains in multiwire drift chambers of the GlueX experiment is described. The accuracy of the technique is estimated based on Monte Carlo generated data with known gain coefficients in the strip signal channels. One of the four detector sections has been calibrated using cosmic rays. Results of drift chamber calibration on the accelerator beam upon inclusion in the GlueX experimental setup are presented.
Surgical and interventional radiographic treatment of dogs with hepatic arteriovenous fistulae.
Chanoit, Guillaume; Kyles, Andrew E; Weisse, Chick; Hardie, Elizabeth M
2007-04-01
To report outcome after surgical and interventional radiographic treatment of hepatic arteriovenous fistulae (HAVF) in dogs. Retrospective study. Dogs (n=20) with HAVF. Medical records of dogs with HAVF were reviewed. Referring veterinarians and owners were contacted by telephone. History, clinical signs, biochemical and hematologic variables, ultrasonographic and angiographic findings, surgical findings, techniques used to correct the HAVF, survival time, and clinical follow-up were recorded. Canine HAVF often appeared to be an arteriovenous malformation rather than a single fistula. Multiple extrahepatic portosystemic shunts were identified in 19 dogs. Surgery (lobectomy or ligation of the nutrient artery) and/or interventional radiology (glue embolization of the abnormal arterial vessels) was performed in 17 dogs. Thirteen dogs were treated by surgery alone, 4 dogs by glue embolization alone, and 1 dog by glue embolization and surgery. Three dogs treated by surgery alone died <1 month later, and 3 dogs were subsequently euthanatized or died because of persistent clinical signs. None of the dogs treated by glue embolization died <1month after the procedure and all were alive, without clinical signs, at follow-up (9-17 months). Overall, 9 of 12 (75%) dogs with long-term follow-up required dietary or medical management of clinical signs. HAVF-related death occurred less frequently after glue embolization than after surgery. Glue embolization may be a good alternative to surgery for treatment of certain canine HAVF.
Gluing for Raman lidar systems using the lamp mapping technique.
Walker, Monique; Venable, Demetrius; Whiteman, David N
2014-12-20
In the context of combined analog and photon counting (PC) data acquisition in a Lidar system, glue coefficients are defined as constants used for converting an analog signal into a virtual PC signal. The coefficients are typically calculated using Lidar profile data taken under clear, nighttime conditions since, in the presence of clouds or high solar background, it is difficult to obtain accurate glue coefficients from Lidar backscattered data. Here we introduce a new method in which we use the lamp mapping technique (LMT) to determine glue coefficients in a manner that does not require atmospheric profiles to be acquired and permits accurate glue coefficients to be calculated when adequate Lidar profile data are not available. The LMT involves scanning a halogen lamp over the aperture of a Lidar receiver telescope such that the optical efficiency of the entire detection system is characterized. The studies shown here involve two Raman lidar systems; the first from Howard University and the second from NASA/Goddard Space Flight Center. The glue coefficients determined using the LMT and the Lidar backscattered method agreed within 1.2% for the water vapor channel and within 2.5% for the nitrogen channel for both Lidar systems. We believe this to be the first instance of the use of laboratory techniques for determining the glue coefficients for Lidar data analysis.
Mondal, Nandan Kumar; Ghosh, Sreenita; Ray, Manas Ranjan
2011-11-01
The effect of glue snuffle on the expression of argyrophilic nucleolar organizer regions (AgNORs), an indicator of ribosome biosynthesis, in epithelial cells of oral mucosa has been investigated. AgNOR was evaluated by cytochemical staining in 148 Indian street boys (median age 12 year) who had different bad addictions like tobacco smoking, chewing and most importantly inhaling glue and 20 age- and body mass index-matched school boys who had no such type of bad habit. Compared with school boys, glue addicted street boys showed remarkably increased number of AgNOR dots per nucleus (9.38±1.84 vs. 3.12±0.87, p<0.001), AgNOR size (1.34±0.52 vs. 0.43±0.02 μm(2), p<0.001) and percentage of AgNOR occupied nuclear area (9.38±2.12 vs. 0.99±0.03%, p<0.001). Increase in number and size of the dots is also higher in tobacco smokers and chewers when compared with school boys but a remarkable difference was recorded in glue addicted boys. The changes in AgNOR expression were positively associated with years of addiction after controlling potential confounders. Thus, glue snuffle appeared to be a risk factor for abnormal cell growth via up-regulation of ribosome biogenesis. Copyright © 2010 Elsevier GmbH. All rights reserved.
Acconcia, Christopher N; Leung, Ben Y C; Goertz, David E
2016-05-01
Serial two-photon microscopy of blood clots with fluorescently tagged fibrin networks was conducted during microbubble-mediated sonothrombolysis to examine the microscale evolution of the resulting erosion front. The development of a complex zonal erosion pattern was observed, comprised of a cell depleted layer of fibrin network overlying intact clot which then underwent progressive recession. The fibrin zone architecture was dependent on exposure conditions with 0.1 MPa causing no erosion, 0.39 MPa resulting in homogenous structure, and combination 0.39/0.96 MPa pulses forming large-scale tunnels. High speed imaging and Coulter counter data indicated the fibrin zone formation process involves the ejection of intact erythrocytes.
Guo, Hai-Dong; Wang, Hai-Jie; Tan, Yu-Zhen; Wu, Jin-Hong
2011-01-01
The high death rate of the transplanted stem cells in the infarcted heart and the low efficiency of differentiation toward cardiomyocytes influence the outcome of stem cell transplantation for treatment of myocardial infarction (MI). Fibrin glue (FG) has been extensively used as a cell implantation matrix to increase cell survival. However, mechanisms of the effects of FG for stem cell transplantation to improve cardiac function are unclear. We have isolated c-kit+/Sca-1+ marrow-derived cardiac stem cells (MCSCs) from rat bone marrow; the cells expressed weakly early cardiac transcription factor Nkx2.5, GATA-4, Mef2C, and Tbx5. Effects of FG on survival, proliferation, and migration of MCSCs were examined in vitro. Cytoprotective effects of FG were assessed by exposure of MCSCs to anoxia. Efficacy of MCSC transplantation in FG was evaluated in the female rat MI model. The MCSCs survived well and proliferated in FG, and they may migrate out from the edge of FG in the wound and nature state. Acridine orange/ethidium bromide staining and lactate dehydrogenase analysis showed that MCSCs in FG were more resistant to anoxia as compared with MCSCs alone. In a rat MI model, cardiac function was improved and scar area was obviously reduced in group of MCSCs in FG compared with group of MCSCs and FG alone, respectively. Y chromosome fluorescence in situ hybridization showed that there were more survived MCSCs in group of MCSCs in FG than those in group of MCSCs alone, and most Y chromosome positive cells expressed cardiac troponin T (cTnT) and connexin-43 (Cx-43). Cx-43 was located between Y chromosome positive cells and recipient cardiomyocytes. Microvessel density in the peri-infarct regions and infarct regions significantly increased in group of MCSCs in FG. These results suggest that FG provide a suitable microenvironment for survival and proliferation of MCSCs and protect cells from apoptosis and necrosis caused by anoxia. MCSCs could differentiate into cardiomyocytes after being transplanted in the border of the infarcted myocardium and form connections with native cardiomyocytes. FG is helpful for MCSC transplantation to repair myocardium and improve cardiac function through promoting the survival, migration, and cardiomyogenic differentiation of MCSCs and inducing angiogenesis.
Infrared Emissivity of Tin upon Release of a 25 GPa Shock into a LiF Window
DOE Office of Scientific and Technical Information (OSTI.GOV)
Turley, W. D., Holtkamp, D. B., Marshall, B. R., Stevens, G. D., Veeser, L. R.
We measured the emissivity of a tin sample at its interface with a lithium-fluoride window upon release of a 25 GPa shock wave from the tin into the window. Measurements were made over four wavelength bands between 1.2 and 5.4 μm. Thermal emission backgrounds from the tin, glue, and lithium fluoride were successfully removed from the reflectance signals. Emissivity changes for the sample, which was initially nearly specular, were small except for the longest wavelength band, where uncertainties were high because of poor signal-to-noise ratio at that wavelength. A thin glue layer, which bonds the sample to the window, wasmore » found to heat from reverberations of the shock wave between the tin and the lithium fluoride. At approximately 3.4 μm the thermal emission from the glue was large compared to the tin, allowing a good estimate of the glue temperature from the thermal radiance. The glue appears to remain slightly colder than the tin, thereby minimizing heat conduction into or out of the tin immediately after the shock passage.« less
Fibrin deposited in the Alzheimer’s disease brain promotes neuronal degeneration
Cortes-Canteli, Marta; Mattei, Larissa; Richards, Allison T.; Norris, Erin H.; Strickland, Sidney
2014-01-01
Alzheimer’s disease (AD) is the most common form of dementia and has no effective treatment. Besides the well-known pathological characteristics, this disease also has a vascular component, and substantial evidence shows increased thrombosis as well as a critical role for fibrin(ogen) in AD. This molecule has been implicated in neuroinflammation, neurovascular damage, blood brain barrier permeability, vascular amyloid deposition, and memory deficits that are observed in AD. Here we present evidence demonstrating that fibrin deposition increases in the AD brain and correlates with the degree of pathology. Moreover, we show that fibrin(ogen) is present in areas of dystrophic neurites and that a modest decrease in fibrinogen levels improves neuronal health and ameliorates amyloid pathology in the subiculum of AD mice. Our results further characterize the important role of fibrin(ogen) in this disease and support the design of therapeutic strategies aimed at blocking the interaction between fibrinogen and Aβ and/or normalizing the increased thrombosis present in AD. PMID:25475538
Code of Federal Regulations, 2012 CFR
2012-07-01
... household glues available to the general public, but do not include potentially hazardous operations such as the use of industrial glues, epoxies, soldering irons, or heating elements. (b) This certificate may...
Code of Federal Regulations, 2014 CFR
2014-07-01
... household glues available to the general public, but do not include potentially hazardous operations such as the use of industrial glues, epoxies, soldering irons, or heating elements. (b) This certificate may...
Code of Federal Regulations, 2010 CFR
2010-07-01
... household glues available to the general public, but do not include potentially hazardous operations such as the use of industrial glues, epoxies, soldering irons, or heating elements. (b) This certificate may...
Code of Federal Regulations, 2011 CFR
2011-07-01
... household glues available to the general public, but do not include potentially hazardous operations such as the use of industrial glues, epoxies, soldering irons, or heating elements. (b) This certificate may...
Code of Federal Regulations, 2013 CFR
2013-07-01
... household glues available to the general public, but do not include potentially hazardous operations such as the use of industrial glues, epoxies, soldering irons, or heating elements. (b) This certificate may...