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Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting.

ABSTRACT: Designing biologically inspired nanoscale molecular assembly with desired functionality is a challenging endeavour. Here we report the designing of fibrin-inspired nanostructured peptide based sealants which facilitate remarkably fast entrapping of blood corpuscles (~28 seconds) in contrast to fibrin (~56 seconds). Our engineered sealants are stabilized by lysine-aspartate ionic interactions and also by N^?(?-glutamyl) lysine isopeptide bond mediated covalent interaction. Each sealant is formed by two peptides having complementary charges to promote lysine-aspartate ionic interactions and designed isopeptide bond mediated interactions. Computational analysis reveals the isopeptide bond mediated energetically favourable peptide assemblies in sealants 1-3. Our designed sealants 2 and 3 mimic fibrin-mediated clot formation mechanism in presence of transglutaminase enzyme and blood corpuscles. These fibrin-inspired peptides assemble to form sealants having superior hemostatic activities than fibrin. Designed sealants feature mechanical properties, biocompatibility, biodegradability and high adhesive strength. Such nature-inspired robust sealants might be potentially translated into clinics for facilitating efficient blood clotting to handle traumatic coagulopathy and impaired blood clotting.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC5529531 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting.

Ghosh Snehasish S Mukherjee Sanchita S Dutta Chiranjit C Chakraborty Kasturee K Gayen Paramita P Jan Somnath S Bhattacharyya Dhananjay D Roy Rituparna Sinha RS

Scientific reports 20170726 1

Designing biologically inspired nanoscale molecular assembly with desired functionality is a challenging endeavour. Here we report the designing of fibrin-inspired nanostructured peptide based sealants which facilitate remarkably fast entrapping of blood corpuscles (~28 seconds) in contrast to fibrin (~56 seconds). Our engineered sealants are stabilized by lysine-aspartate ionic interactions and also by N<sup>ε</sup>(γ-glutamyl) lysine isopeptide bond mediated covalent interaction. Each sealant ...[more]

PMID: 28747673

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Project description: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.

Project description:Background Evidence comparing fibrin sealants (FSs) in surgery are limited. This study evaluated the efficacy and safety of FSs, and manual compression in peripheral vascular surgery. Methods A systematic review of randomized trials was conducted in Medline, Embase, and Cochrane databases within the last 15 years. Data were available to conduct a network meta-analysis (NMA) in peripheral vascular surgery. Fibrin sealant treatment arms were further broken-down and assessed by clotting time (i.e., 2-min [2C] or 1-min [1C]). The primary efficacy outcome was the proportion of patients achieving hemostasis by 4 min (T4). Treatment-related serious and non-serious adverse events (AEs) were qualitatively assessed. Results Five studies (n = 693), were included in the NMA. Results predicted VISTASEAL 2C, followed by EVICEL 1C, had the highest probability of achieving T4. Compared with manual compression, significant improvements in T4 were found with VISTASEAL 2C (relative risk [RR] = 2.67, 95% CrI: 2.13–3.34), EVICEL 1C (RR = 2.58, 95% CrI: 2.04–3.23), VISTASEAL 1C (RR = 2.00, 95% CrI: 1.45–2.65), and TISSEEL 2C (RR = 1.99, 95% CrI: 1.48–2.60). TISSEEL 1C was not significantly different than manual compression (RR = 1.40, 95% CrI: 0.70–2.33). Among FSs, VISTASEAL 2C was associated with a significant improvements in T4 compared with VISTASEAL 1C (RR = 1.33, 95% CrI: 1.02–1.82), TISSEEL 2C (RR = 1.34, 95% CrI: 1.05–1.77), and TISSEEL 1C (RR = 1.90, 95% CrI: 1.18–3.74). Treatment-related serious and non-serious AE rates were typically lower than 2%. Conclusions In peripheral vascular surgeries, VISTASEAL 2C and EVICEL 1C were shown to have the highest probabilities for achieving rapid hemostasis among the treatments compared. Future studies should expand networks across surgery types as data become available. Highlights • Fibrin sealants can control perioperative bleeding, yet comparative evidence is limited.• This network meta-analysis compared fibrin sealants and compression in peripheral vascular surgery.• VISTASEAL and EVICEL had the highest probability of achieving hemostasis by 4 min.• These results show differences exist between fibrin sealants in peripheral vascular surgery.

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Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting.

Publications

Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting.

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