Elsevier

Biomaterials

Volume 23, Issue 10, May 2002, Pages 2249-2254
Biomaterials

Reproducibility of the mechanical properties of Vivostat® system patient-derived fibrin sealant

https://doi.org/10.1016/S0142-9612(01)00359-3Get rights and content

Abstract

Conventional “autologous” fibrin sealants, prepared from fibrinogen concentrates are inconsistent in their physical properties; this reflects the wide variation in the fibrinogen level of the single donor plasma from which they are made. In contrast, the Vivostat® System produces a fibrin sealant of reproducible concentration and mechanical properties that are independent of the source plasma fibrinogen concentration. Fibrin solution concentrations prepared with the Vivostat® System were 22.0±0.7 mg/ml (95% CI) with a coefficient of variation [CV] of 10.6% from samples of source plasma with a range of fibrinogen concentration between 1 and 6 mg/ml (mean 3.28±0.38 mg/ml (95% CI), 37% CV). Values of viscoelastic and tensile parameters after 11 min and 1 h, respectively, were: storage modulus (G′) 891.5±72.9 Pa, 16.2% CV; loss modulus (G″) 98.7±9.8 Pa, 23.2% CV; loss tangent (tan δ) 0.1093±0.0054, 9.8% CV; tensile strength 33.2±2.6 kPa, 24.7% CV; extension at break 103±13%, 22.6% CV; Young's modulus 12.0±1.0 kPa, 16.6% CV. In the clinical setting this reproducibility provides the surgeon with a patient-derived fibrin sealant that can be expected to perform similarly from patient to patient.

Introduction

A major criticism of conventional patient-derived fibrin sealants is the poor reproducibility of their properties and clinical performance [1]. These sealants have been prepared historically by the mixing of a fibrinogen concentrate (e.g. cryoprecitate), obtained from an individual plasma donation, and thrombin that is usually sourced from pooled human or animal plasma. Plasma fibrinogen levels vary considerably between individuals, being affected by factors including age, sex, race, body mass index, alcohol intake, and smoking status [2], [3], [4], [5], as well as certain disease states [6], [7], [8]; values of 2–6 mg/ml are typical of patients undergoing surgery. These variations in fibrinogen concentration are reflected as similar variations in concentration of fibrin sealants prepared from individual plasma donations [9], [10], [11]; poor reproducibility in physical properties is an inevitable consequence.

The Vivostat® System1 (Vivolution A/S, Denmark), a medical device for the preparation and application of patient-derived fibrin sealant, free from added thrombin, was designed to compensate for such variations in plasma fibrinogen concentration, ensuring a reproducible sealant from patient to patient [9]. The Vivostat System utilises an enzymatic reaction to concentrate patient-derived fibrinogen in the form of fibrin I polymer, which is subsequently separated from the reacted serum and dissolved in a small volume of pH 4 buffer. This reaction has been optimised with respect to time, temperature and enzyme concentration such that a constant mass of fibrinogen is converted to fibrin I in a set time. This results in a degree of control of the fibrin I concentration due to the fact that as the plasma fibrinogen concentration increases, the fibrin I polymer recovery decreases. The Vivostat processor also incorporates a sensor system for further enhancement of the control of fibrin concentration [12]. This assesses fibrin mass, which is proportional to fibrin I volume, and enables automatic adjustment of the dilution level employed to obtain a consistent fibrin I concentration in the final sealant.

The mechanical properties of fibrin sealants depend not only on their fibrin concentration, but may also be influenced by other biochemical or chemical factors in the fibrin I solution [13], [14], [15]. Although the optimum mechanical properties of fibrin sealants have yet to be defined, wide variations in the physical properties of sealant from sample to sample are likely to be reflected as inconsistency in clinical performance. The present study was undertaken to evaluate the reproducibility in the fibrin concentration and mechanical (viscoelastic and tensile) properties of Vivostat sealant.

Section snippets

Materials and methods

Vivostat Systems were supplied by ConvaTec Ltd, Deeside, UK. Vivostat-derived fibrin I solutions were prepared from freshly donated blood in the automated Vivostat Processor and used within 1 h. Vivostat-derived fibrin sealant gels were prepared by co-delivery of individually prepared samples of fibrin I solution with pH 10 buffer (in a 7:1 ratio) using the Vivostat Spraypen® applicator.

The fibrin I concentrations of the fibrin I solutions were measured using a method based on the selective

Fibrin concentration

The mean concentration of fibrin I solutions obtained from the processing of 41 samples was of 22.0±0.7 mg/ml (95% CI); the range was 17.8–26.5 mg/ml and the CV was 10.6%. The mean plasma fibrinogen concentration of the blood used to prepare these samples was 3.28±0.38 mg/ml (95% CI) (range 1.04–5.96 mg/ml, 37% CV). The mean fibrin volume was 4.77±0.25 ml (95% CI) (range 3.20–6.02 ml, 16% CV).

Rheometry

The viscoelastic properties of 21 fibrin gels were monitored at approximately 20 s intervals over a period of

Discussion

As well as having necessary adhesive properties, good clinical performance of fibrin sealants depends on having an appropriate balance of tensile and viscoelastic properties to provide the necessary strength and conformability for formation and maintenance of a good physical barrier when applied to tissues. Although other proteins and chemicals may influence the physical properties, many studies have demonstrated that fibrin concentration is a key factor in determining the physical and adhesive

References (26)

  • G.Y.H. Lip

    Fibrinogen and cardiovascular disorders

    Q J Med

    (1995)
  • B. Casali et al.

    Fibrin glue from single-donation aaautologous plasmapheresis

    Transfusion

    (1992)
  • M.S. Park et al.

    Biochemical aspects of autologous fibrin glue derived from ammonium sulphate precipitation

    Laryngoscope

    (1993)
  • Cited by (28)

    • Development and evaluation of a spray applicator for platelet-rich plasma

      2018, Colloids and Surfaces B: Biointerfaces
      Citation Excerpt :

      Specific disadvantages of single-fluid nozzles for spraying blood products are an inhomogeneous film, clogging and limited control over the spray [21]. Disadvantages of currently used two-fluid systems such as the Vivostat® system (Vivostat A/S, Lillerod, Denmark) for application of blood products [35] and the skin gun [13,14] for applying skin lysates are complexity, weight and only partial sterilizability. In a review of spray applicators for fibrin sealants, a ranking system was suggested [21], upon which we based the requirements for our novel spray applicator.

    • Wound healing in urology

      2015, Advanced Drug Delivery Reviews
      Citation Excerpt :

      They can be produced from pooled blood sources or a single blood donor. They consist of human fibrinogen, fibronectin, factor XIII and plasminogen [39]. They are reconstituted in a solution containing aprotinin, which is a bovine derived protease inhibitor.

    • Viscoelastic adhesive mechanics of aldehyde-mediated soft tissue sealants

      2008, Biomaterials
      Citation Excerpt :

      Highly reactive cyanoacrylate derivatives achieve relatively high strength bioadhesion but in doing so may reduce native viscoelasticity as a consequence of low molecular weight tissue crosslinking. Conversely, less adherent fibrin sealants will likely maintain tissue viscoelasticity but cannot provide the mechanical strength necessary for wound stabilization and other clinical applications [17]. A viscoelastic model of adhesive mechanics could meaningfully describe tissue–material interactions and facilitate correlation of mechanical properties with ultimate function.

    • New method to prepare autologous fibrin glue on demand

      2007, Translational Research
      Citation Excerpt :

      Furthermore, the current cost of the sealant produced by the autologous plasma/protamine method is the cost of the protamine, which would be approximately $10 for each 10 mL of plasma to harvest 2.0 mL of sealant containing 15-mg fibrinogen/mL fibrin sealant. A major criticism of conventional autologous fibrin sealants prepared from plasma without fibrinogen concentration is the poor reproducibility of their mechanical properties and clinical performance.38 Plasma fibrinogen levels vary considerably between individuals, being affected by age, sex, race, alcohol intake, and smoking, as well as certain disease states.

    View all citing articles on Scopus
    View full text