Adhesive Use in Oral and Maxillofacial Surgery

Transcription

1 Adhesive Use in Oral and Maxillofacial Surgery Michael J. Buckley, DMD, MBA, MS a,b, *, Eric J. Beckman, PhD c,d KEYWORDS Tissue adhesives Adhesives for bone fixation Cyanoacrylates Fibrin sealants Collagen-based sealants Synthetic polymer-based materials Protein-based sealants The tissue adhesive market is a vibrant and dynamic sector with emerging technologies and innovative concepts for cutting-edge applications. Presently in oral and maxillofacial surgery, adhesives have a minimal role, but this is changing rapidly. In oral and maxillofacial surgery, closure of soft tissue wounds is primarily done with mechanical devices, such as sutures and staples. To close larger soft tissue wounds or develop large soft tissue flaps in cosmetic and reconstructive procedures, clinicians use mechanical devices and apply drains that help evacuate dead spaces to prevent hematomas and seromas. Similarly bone fixation in oral and maxillofacial surgery is primarily done with external fixation, such as maxillomandibular fixation, or with internal fixation using small bone plates and screws. The emerging adhesives and sealants are likely to have clinical applicability in oral and maxillofacial surgery soon and accelerate this clinical change. IDEAL PROPERTIES OF TISSUE ADESIVES The ideal tissue adhesive must be biodegradable and biocompatible. To be effective, it must have both significant cohesive (covalent bonding of glue molecules to each other) and adhesive (bonding of glue molecules to adjacent tissue) properties. To be biocompatible, tissue adhesives must pass both acute and subacute toxicity tests and have minimal cytotoxicity. The adhesive must have a suitable setting time and be user friendly, requiring little preparation time. It should also have no special storage or shipping requirements. It must be relatively hydrophilic so it readily spreads on wet surfaces at body temperature, and have adequate working time for the given application. The adhesives must be strong, yet flexible, with an elastic modulus similar to that of the tissue being glued. Lastly, the adhesives must have minimal heat generation (exothermic) characteristics and degrade with minimal inflammatory response. At the moment, no adhesives on the market fulfill all of these requirements. Surgeons have been using tissue sealants and adhesives since the early nineteenth century. 1 There are presently four types of tissue adhesives: fibrin sealants, collagen-based sealants, synthetic polymer-based materials, and protein-based sealants. In 2000, fibrin sealants accounted for 86% of the total tissue sealant market while protein-based sealants accounted for 12% and synthetic polymer-based materials represented 2%. 2 FIBRIN ADESIVES In the early 1940s, the combination of fibrin and thrombin was first used as an adhesive. These a Private Practice, 31 N Maple Avenue, Greensburg, PA 15601, USA b University of Pittsburgh School of Dental Medicine, 3501 Terrace Street, Pittsburgh, PA 15213, USA c Cohera Medical Inc, Pittsburgh, PA, USA d University of Pittsburgh School of Engineering, 3800 O ara Street, Pittsburgh, PA 15213, USA * Corresponding author. Private Practice, 31 N Maple Avenue, Greensburg, PA address: mbuckley@coheramed.com Oral Maxillofacial Surg Clin N Am 22 (2010) doi: /j.coms /10/$ see front matter ª 2010 Elsevier Inc. All rights reserved. oralmaxsurgery.theclinics.com

2 196 Buckley & Beckman fibrin sealants and glues were developed and used extensively in the 1960s with donor-preserved and autologous-donated plasma as the source of the coagulation components. In 1977, however, the US Food and Drug Administration (FDA) revoked the license for the commercial use of fibrin sealants and glues from donor-preserved human plasma because of the possibility of disease transmission. 3 5 The fibrin glues presently on the market are Tisseel (Baxter International Inc, Deerfield, Illinois) and emaseel (aemacure Corp, Montreal, Canada). The fibrin glues in head and neck surgery are primarily used as hemostatic agents over large surface areas and are very effective for that use. Fibrin glues, however, require mixing of several different components on the back table, which takes 20 to 40 minutes, before they can be used. Fibrin glues are good hemostatic agents but are poor adhesives as they exhibit a very weak bond. They are, however, entirely biodegradable and biocompatible. 6 COLLAGEN- AND PROTEIN-BASED SEALANTS Collagen- and protein-based adhesives and sealants are made up of connective tissue components used as a two-part adhesive by taking advantage of the ability of the components to cross-link upon mixing. Collagen, when crosslinked with glutaraldehyde, forms a protein-based sealant that can seal against both air and fluid leakage. This two-part sealant also creates a weak adhesive bond to adjacent tissue and is sometimes referred to as an adhesive for that reason. Protein-based adhesives (eg, BioGlue [CryoLife, Kennesaw, Georgia]) have several disadvantages: Because they are made from bovine serum albumin, they pose a small risk for transmission of disease and contain a foreign protein that can cause hypersensitization. 7 More importantly, they use glutaraldehyde as the cross-bonding agent, which is a neurotoxin. Degradation of these sealants is very slow and strong inflammatory responses can result. Because of their weak adhesive strength, their use in craniomaxillofacial surgery is primarily in free flap surgery as a sealant around a vascular anastamosis. 8,9 Another of the two-part sealants, is DuraSeal (Confluent Surgical, Inc, Waltham, Massachusetts), an FDA-approved product for use in dural sealing. When employed for appropriate dural closure, DuraSeal can be used to complete the watertight closure necessary in this tissue. Dura- Seal is a polyethylene glycol based hydrogel that is synthetic, absorbable, and easily applied. It is designed such that each of its two parts contains polyethylene glycol polymers with complementary functional groups at the polymer chain ends. When mixed, these complementary groups react with each other, leading to a rapid cure. Its use as an adhesive, however, is limited because of its poor adhesive strength. DuraSeal is readily degradable (the linkages formed during curing are hydrolytically cleaved) and biocompatible. 10 CYANOACRYLATES Cyanoacrylates (superglues) have been used for years as wound-closure materials. Octyl-cyanoacrylates and butyl-cyanoacrylates have been recently used as skin-closure adhesives with good success. All of the cyanoacrylates operate as adhesives in similar manners. They are applied as mononers, which then rapidly polymerize to a high molecular-weight material The presence of the cyano group on the acrylate monomer enables initiation of polymerization (curing) simply by water or amine groups present on proteins, a characteristic not present in typical acrylates. Conventional superglue (methyl cyanoacrylate) cures to a hard, brittle material, whereas the octyl and butyl analogs used as tissue adhesives form a more resilient material once cured. While exhibiting a strong adhesive bond once cured, cyanoacrylates do not biodegrade to any real extent and can induce a significant inflammatory response given their hydrophobic nature. Their use has generally been limited to superficial wounds. Cyanoacrylate tissue adhesives form a strong bond across tissue-wound edges, enabling normal healing to occur below the seal. They are marketed to replace small sutures in incision and laceration repairs. These adhesives have been shown to save time and provide a flexible waterresistant protective coating that will seal head and neck wounds from water exposure and contamination. They can be used safely in small wounds, but also in larger wounds where subcutaneous sutures are needed and a watertight sealant is appropriate. There is a small exothermic reaction during curing, but the patient does not usually feel the temperature rise. These cyanoacrylates have been shown to have some antimicrobial properties. 14 POLYURETANE ADESIVES Polyurethane adhesives exhibit a wide range of physical and mechanical properties that make them attractive candidates for biomedical use. Created by the reaction of polyester- or polyether-polyols with polyfunctional isocyanates, polyurethane polymers are frequently used in

3 Adhesive Use in Oral and Maxillofacial Surgery 197 O=C=N + O -C -O O (3) Lysine di-isocyanate (LDI) (1) Glycerol O=C-N O= O -C -O-C-N O O=C-N Fig. 1. Reaction of glycerol and lysine di-isocyanate (LDI). LDI is composed of a lysine core (black) with two isocyanate groups (blue). One glycerol (red) reacts with three LDI molecules to produce an isocyanate-capped glycerol prepolymer. The reaction of the hydroxyl groups on glycerol with the isocyanate groups on LDI produces a urethane linkage (green). The resultant prepolymer has three unreacted isocyanate groups remaining. medical applications, such as heart valves, dialysis membranes, breast implants, and aortic grafts. When employed as an adhesive, a urethane prepolymer generally has an oligomeric (rather than polymeric) structure and contains terminal (ie, at chain ends) isocyanate groups (Fig. 1). These groups react readily with hydroxyls and amines found in tissue, forming a strong bond with the surface. In addition, the presence of water leads to rapid curing through the transformation of some of the isocyanate groups to amines, followed by reaction of these amines with nearby isocyanates to create urea crosslinks. Although various adhesive and nonadhesive biodegradable polyurethanes have been synthesized, current available synthetic adhesive components have met with limited commercial success for a number of reasons. For example, a number of such compositions exhibit unacceptable toxicity arising, for example, from the cytotoxicity of the degradation products of the isocyanates used in the synthesis of these adhesives. Isocyanates are generated from the analogous amines, and several of the aromatic amines used to create commercial isocyanates (those used in foam bedding and seating) have been shown to be carcinogenic, rendering such isocyanates entirely unsuitable for use in medical adhesives. In addition, early attempts at using commercial polyisocyanates and polyols in medical adhesives led to cured products that were too hydrophobic to degrade quickly. Recently in development and beginning initial clinical trials is a lysine-derived urethane tissue adhesive that may prove ideal for fixation of deep wounds. This adhesive is biocompatible, resorbable, and nontoxic and could dramatically improve the field of wound closure and hence significantly advance surgical care. This adhesive is best used on plainer tissues and will be suitable for reducing or eliminating dead space in large traumatic wounds and for developing soft tissue flaps. Its use in eliminating dead space and preventing seromas and hematomas in cosmetic surgery procedures, such as in face lifts and forehead lifts, will likely be significant. In a recent study using a canine abdominoplasty model (Fig. 2), use of the lysine-based urethane adhesive decreased Fig. 2. Comparison of test lysine di-isocyanate adhesive and control in canine abdominoplasty model. (From Gilbert TW, Badylak SF, Gusenoff J, et al. Lysinederived urethane surgical adhesive prevents seroma formation in a canine abdominoplasty model. Plast Reconstr Surg 2008;122:95 102; with permission.)

4 198 Buckley & Beckman Failure Strength (N/cm^2) Time Control Strain (N/cm^2) SD Glue Strain (N/cm^2) SD 1 hours hours hours week weeks weeks hours 12 hours 24 hours 1 week 2 weeks 4 weeks Time wound exudates by 97%, versus the control, with minimal inflammatory response. As shown in Fig. 3, tensile strengths were measured for control wounds and wounds with a polyurethane adhesive at 1 hour, 12 hours, 24 hours, and 1 week. At all time points, tensile strengths of the polyurethane-closed wounds were stronger than that of a naturally healing wound at 1 week. istologic analysis revealed no tissue reaction, minimal inflammation, and no necrosis of muscle-wound tissue. Planar wounds in the head and neck region could greatly benefit from an adhesive with the chemical proprieties and surgical strength to eliminate the dead space. The various building blocks of the polyurethane adhesives can be blended in different proportions to create adhesives with a useful range of physical properties and cure times. Polyurethane created via moisture curing of the prepolymer simply degrades to an initial hydroxyl-containing compound plus lysine, small amounts of ethanol, and carbon dioxide. BONE ADESIVE Control Glue Fig. 3. Strength comparison of TissuGlue (Cohera Medical, Inc, Pittsburgh, Pennsylvania). Tensile strengths were measured for control wounds and wounds with TissuGlue at 1 hour, 12 hours, 24 hours, and 1 week. At all time points, tensile strength of wounds with TissuGlue were stronger than that of a naturally healing wound at 1 week. A particular problem in oral and maxillofacial surgery is bone fixation of small pieces of bone where use of bone screws and bone plates is impossible or impractical. These applications might include not only small fragments of bone in the craniomaxillofacial region, but also fixation of intracapsular fractures where the use of screws and bone plates is precluded. A bone adhesive strong enough to hold bony fragments in their original anatomic position and enable osseous union between these fragments would be of great benefit. Presently, a polyurethane adhesive with building blocks has been designed to give significant bony strength, and still allow for osseous union to occur SUMMARY Presently, tissue adhesives and sealants have a limited use in oral and maxillofacial surgical procedures. 17 Skin closure occurs regularly with cyanoacrylate adhesives Sealing of dural tears in conjunction with dural closure has been shown to be very successful. With the development of more head and neck reconstructive procedures and cosmetic procedures, demand will increase for better surgical adhesives. Clinical trials are beginning for newly developed adhesives with the chemical characteristics, the safe reabsorptive profile, and the adhesive strength necessary to benefit oral and maxillofacial surgery patients in the near future. Adhesives for bone fixation, while in early development, also show a promising chemical profile and will be of significant benefit to oral and maxillofacial surgical patients. REFERENCES 1. Currie LJ, Sharpe JR, Martin R. The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. Plast Reconstr Surg 2001;108(6): Frost and Sullivan. US market for hemostats-tissue sealants-tissue adhesives and adhesion prevention products. Available at: Accessed May 1, Carless PA, Anthony DM, enry DA. Systemic review of the use of fibrin sealant to minimize perioperative allogeneic blood transfusion. Br J Surg 2002;89(6): Jackson MR, Alving BM. Fibrin sealant in preclinical and clinical studies. Curr Opin ematol 1999;6(6): Jackson MR. Fibrin sealants in surgical practice: an overview. Am J Surg 2001;182(2 Suppl 1):S Silver F, Wang M-C, Pins GD. Review: preparation and use of fibrin glue in surgery. Biomaterials 1995; 16(2): Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombine exposure. Transfusion 2002;42(1): Passage J, Jalali, Tam RK, et al. BioGlue surgical adhesive an appraisal of its indications in cardiac surgery. Ann Thorac Surg 2001;72(2):

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