Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.

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Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Elastomeric biomaterials for tissue engineering

Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.

Tough adhesives for diverse wet surfaces

Platelet gel: An autologous alternative to fibrin glue with applications in oral and maxillofacial surgery

This invention provides a fibrin sealant bandage or dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides, polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant bandage or dressing.

Supplemented and unsupplemented tissue sealants, methods of their production and use

Fibrin sealants (FS) are the most successful tissue adhesives to date. They have many advantages over adhesive technologies such as cyanoacrylates and marine adhesives in terms of biocompatibility, biodegradation and hemostasis. There are several commercial products in Europe but none in the United States due to the current regulatory stance against pooled plasma blood products. Blood banks and interested investigators have implemented single- and patient autologous-donor production methods with some success. This article will review the history of FS research and development and describe the chemistry of fibrin(ogen) and the production of commercial and research products. Fibrin sealant and purified fibrin characterization is compared and contrasted. The material and adhesive properties are described, and a survey of the clinical applications in which FS has been used is included as well.

Fibrin Sealant Adhesive Systems: A Review of Their Chemistry, Material Properties and Clinical Applications:

A 2-year experience with laboratory and clinical applications of fibrin glue is presented. An autologous technique, which eliminates the danger of multidonor preparations, has been developed in our blood bank. While one can obtain different fibrinogen concentrations from the same amount of a patient's blood, in vitro mechanical testing demonstrated that at higher fibrinogen concentrations there is an increase in shear adhesive strength. Evaluation of skin-graft take in 16 Sprague-Dawley rats did not demonstrate significant differences in healing when adhesive use was compared with suture technique. In a clinical study, four different groups of patients (facial burns, hand burns, difficult graft sites, and miscellaneous surgical applications) benefited from autologous or single-donor fibrin glue for a total of 82 cases. There are several distinct advantages to the use of fibrin adhesive: The autologous technique eliminates the risk of transmissible viral diseases (AIDS, hepatitis); it can be used as a sealant in the treatment of seromas, dural leaks, and lymphoceles; and it improves hemostasis and early graft adherence. Face and hands are resurfaced with sheet grafts in a single procedure, obtaining a better aesthetic result with complete graft take and immediate start of physical therapy. Neither sutures nor pressure dressings are required. The minimal postoperative care associated with early return to normal activities seems to increase the satisfaction of patients and nurse personnel.

Experimental and clinical applications of fibrin glue.

A series of analyses were performed on fibrin-based adhesives to describe their failure characteristics. Two test methods were used: uniaxial, monotonic tensile testing of the bulk material, and blister testing using fresh porcine-source skin graft as the adherend. Two fibrin concentrations, high (HFC), and low (LFC), were used to investigate the effects of the gel matrix density upon mechanical properties. In tensile tests, fibrin gels strain hardened, as functions of percent strain and of strain rate. An increase in modulus of elasticity (E) was seen with increasing strain and strain rate at both tested fibrin concentrations. Mode I failure mechanisms were predominant. Both adhesives appeared to fracture from the outer edge to the interior of the specimen at slower strain rate tests. This trend reversed as strain rate increased, becoming a classic "cup and cone" ductile fracture. Syneresis occurred at both concentrations at lower strain rates, but was more pronounced for the LFC. Ultimate tensile strength and E were greater for the HFC than for the LFC at all strain rates, decreasing with increasing strain rate. In the blister test, the failure locus changed from cohesive to adhesive as the strain rate was increased for the HFC. Failure of fibrin gels likely occurs by percolation of the pressurized saline, displacing the entrapped liquid phase of the gel in regions of relatively low moduli and strength, leading to fracture of the matrix. For LFC, the overall fracture locus remained predominantly cohesive regardless of strain rate. Burst strength and failure energy were higher for HFC than for LFC. It would appear that fibrin acts more as a viscous liquid than a rubberlike/elastic material at lower concentrations because adhesive failures had a higher burst strength and fracture energy (Gc) than did cohesive failures.

Failure characteristics of multiple-component fibrin-based adhesives.

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.

A method to determine shear adhesive strength of fibrin sealants.

ADHESIVE TECHNOLOGIES History of Tissue Adhesives Commercial Pooled-Source Fibrin Sealant Mussel Adhesive Protein Fibrin-Collagen Composite Tissue Adhesive Soldering Is a Superior Alternative to Fibrin Sealant LABORATORY EVALUATION Kinetic and Mechanical Parameters of Fibrin Glue Surgical Tissue Adhesives: Host Tissue Response, Adhesive Strength and Clinical Performance Biological and Rheological Properties of a Virally Inactivated Fibrin Glue (Biocolr): Comparison to an Autologous Fibrin Glue Assessment of Restored Tissue Elasticity in Prolonged in vivo Animal Veterinary Hemaseelr: Ex vivo and in vivo Studies on Bovine Fibrin Sealant LABORATORY APPLICATIONS Wound Healing Applications of Fibrin Sealants Fibrin Sealant: A Versatile Delivery Vehicle for Drugs and Biologics Sustained Release of Antibiotics from Fibrin Sealant Bone Induction by Demineralized Bone Powder and Partially Purified Osteogenin Using a Fibrin-Sealant Carrier Fibrin Sealant as a Delivery Vehicle for Sustained and Controlled Release of Chemotherapy Agents Experimental and Clinical Considerations: Craniofacial Surgery and Bone Metabolism CLINICAL APPLICATIONS AND INVESTIGATIONS Fibrin Sealant and the U.S. Food and Drug Administration Review Utilization of Fibrin Glue in Craniofacial and Facial Plastic Surgery Tissue Adhesives in Plastic and Reconstructive Surgery Clinical Applications of Tissue Adhesives in Aesthetic and Reconstructive Surgery Surgical Adhesives in Otolaryngology A Review of Nonsuture Peripheral Nerve Repair Clinical Use of Fibrin-Based Composite Tissue Adhesive in Otology and Neurotology Clinical Applications of Fibrin Sealant in Thoracic and Cardiovascular Surgery

David H. Sierra

Papers

Fibrin Sealant Adhesive Systems: A Review of Their Chemistry, Material Properties and Clinical Applications:

Experimental and clinical applications of fibrin glue.

Failure characteristics of multiple-component fibrin-based adhesives.

A method to determine shear adhesive strength of fibrin sealants.

Surgical adhesives and sealants : current technology and applications