Surgical Glue: A Brief Overview

Abstract

Wound closure is one of the cardinal steps of surgical procedure, and suturing is the most widely used method of wound closure. The process of suturing usually prolongs the length of surgery and increases the patient’s risk of anesthesia awareness. It has several disadvantages, including iatrogenic trauma to the tissue, pain, increased risk of infection and inflammation, delayed healing, and inability to provide an immediate seal. Lately, there has been a growing interest in surgical glues as a substitute to suturing. However, surgical glues have their own unique disadvantages, which need to be addressed in designing “ideal” surgical glue.

Keywords: Surgical Glue; Hemostat; Sealant; Adhesive

Abbreviations

CSF: Cerebrospinal Fluid; CNS: Central Nervous System; FDA: Food and Drug Administration; PEG: Polyethylene Glycol; HLAA: Hydrophobic Light-Activated Adhesive; PGSA: Poly Glycerol Sebacate Acrylate

Introduction

Surgery (from Greek “hand work”) is “the branch of medicine that relates to body injuries, deformities, and morbid conditions that require being remedied by operations or instruments” [1]. It typically involves cutting of tissues and closure of iatrogenic or traumatic wounds. The tissues that are closed can be static, such as skin, or dynamic, such as contracting myocardium. The environment can be dry, such as a bone, or wet, such as the lumen of a blood vessel. Traditionally, surgical wounds have been closed with a variety of sutures with different sizes, strengths, and compositions. Suturing typically achieves its intended goal of approximating the tissue at the wound site until the physiologic “seal” is accomplished, however it has disadvantages. The process of passing the needle can be traumatic and will cause additional pain. Often, it has to be removed and requires a second procedure. The suture tracts themselves can serve as conduit to secondary infections and necessitate antibiotic treatment, and the suture material can cause local tissue inflammation and delay healing. Although suturing is effective in approximating the edges of the tissue, it does not achieve immediate sealing of the wound and may be associated with prolonged bleeding [2]. Lastly, the process of suturing can be time-consuming and subject the patient to prolonged risk of anesthesia and increase the cost of healthcare. Therefore, with increasing popularity of minimally invasive surgery [3,4], which is not associated with large incisions, and advancement in chemical science, there is a growing need, application, and availability of surgical glues for different surgical subspecialties [5-10].

The currently available surgical glues, however, have shortcomings: they can be easily washed out under dynamic conditions; they can be toxic to the tissue; some are not strong enough; they can be difficult to reposition after initial application; and some can be destabilized by the presence of blood. There are a variety of surgical glues that have strong points (e.g. biodegradable, easy to handle, strength, suture-free, etc.), but there is no single ideal glue that addresses all shortcomings.

William D. Spotnitz provided a useful system of classifying surgical glues divided into groups and categories [11-14]. The groups are based on their purpose (hemostats, sealants, and adhesives) and categories based on their functional characteristics and mechanism of action.

The purpose of topical hemostats is to accelerate hemostasis by causing blood clot formation and it requires the presence of blood. The sealants stop leakage of fluid from tissue openings such as CSF from CNS, but the fluid does not have to be blood. The adhesives bond tissue together, such as a surgical incision wound.

It is notable that some agents can have multiple purposes, such as a fibrin sealant that can act as a hemostat, a sealant, and an adhesive. A significant number of surgical glues functionally depend on a physiologic coagulation cascade. Two of the essential components ofthe coagulation cascade are thrombin and fibrinogen. In the presence of calcium ions, thrombin cleaves the fibrinogen chains. The resulting fibrinogen monomers eventually polymerize and form a fibrin clot. These steps are independent of the coagulation pathway and can be reproduced artificially. The rate of the clot formation increases with thrombin concentration. The strength of the clot, on the other hand, depends on the concentration of fibrinogen.

Porcine gelatin, bovine collagen, oxidized regenerated cellulose, and polysaccharide spheres

These compounds work by creating a mechanical barrier and a surface to stop hemorrhage or accelerate blood clotting. Hence, they act as hemostats. They are relatively safe and easy to use. However, swelling and infection are drawbacks. Removal of the glue is recommended after achieving hemostasis to minimize side effects [6,15,16].

Bovine thrombin, pooled human thrombin, and recombinant thrombin

These compounds essentially provide concentrated levels of thrombin for rapid conversion of fibrinogen to a fibrin clot. They act as hemostats and can be effective in stopping both local and diffuse hemorrhage. They are relatively easy to use, but the side effects include antibody formation (bovine) that can lead to coagulopathy. Viral or prion disease may potentially be associated with pooled human plasma. Allergic reactions to hamster or snake protein are possible for recombinant products. More importantly, intravascular use of these products is counter-indicated [17,18].

  

    
Glue #
    
Function
    
Strengths
    
Drawbacks
  
  

    
1
    
Act as hemostats
    
Safe and easy to use
    
Can cause    swelling and infections
  
  

    
2
    
Performsimilar to hemostats
    
Safe and easy to apply
    
Antibody formation, plausible coagulopathy, and    allergic reactions
  
  

    
3
    
Hemostat-likevia fibrin clot
    
Easy to apply and more effective than 1 and 2
    
Similar to 1 and 2. Swelling, allergic reactions    and infections
  
  

    
4
    
Hemostat, sealant, and adhesive
    
Very versatile, FDA approved, commercially    available, and effective
    
Potential side effects are viral or prion    disease, antibody formation, allergic reactions, and swelling
  
  

    
5
    
Moderately strong sealant
    
User friendly, low-cost, and biodegradable
    
Can cause significant swelling and not very    effective on wet surfaces
  
  

    
6
    
Strong sealant and adhesive
    
User friendly and strong glue
    
Side effects are tissue necrosis and adhesive    embolism
  
  

    
7
    
Strong adhesive
    
Readily available, easy to use, and instant bond
    
Limited to external use only and can cause foreign body reaction
  
  

    
8
    
Adhesive
    
Biodegradable, reduce dead space, and absorbed by    the body
    
Increase surgical time for a few minutes. Not yet    approved for sale or marketing in the USA.
  
  

    
9
    
Adhesive, used to seal defects in the heart and    arteries
    
Strong and flexible, activated by UV light.
    
Promising adhesive. However, only animal models    have been studied
  

Table 1:  Summary of functions, strengths, and drawbacks of current surgical glues.