The tissue adhesives are biomaterials used in the treatment of hemostasis, wound closure and tissue repair [
1]. Compared to sutures, the advantages of using these adhesives relate to their ability to polymerize
in situ, to adapt to complex wound contours and dimensions (sufficient mechanical flexibility), to be biocompatible, to possess adequate mechanical and physical properties (such as burst strength, tensile strength and shear strength and shear resistance), to have high bond strength to moist tissue or organs, and finally to be easily applied [
2,
3]. They fall into two categories: (i) tissue adhesives based on natural polymers (fibrin, albumin and gelatin); (ii) synthetic tissue glues, based on cyanoacrylate, poly(ethylene glycol) (PEG), catechol and methacrylic anhydride [
4,
5,
6]. The design of an effective tissue adhesive is related to a careful tissue-adhesive interface that includes an adhesion layer, where the adhesive makes intimate contact with the tissue, and an adhesive matrix, which consists of the polymer network of the substances that make up the adhesive. The adhesion layer anchors to the underlying tissue through chemical, physical or covalent and non-covalent bonds; while the adhesive matrix provides structural support to the adhesion layer and determines the chemical and physical characteristics of the adhesive [
7]. From the 1950s onwards, cyanoacrylate glue was only used for wound closure; in 2000 it was finally approved its use for internal use in the treatment of arteriovenous malformations as a liquid gel embolic system [
6]. Cyanoacrylate comes in four forms: methyl-2-cyanoacrylate (2-MCA),ethyl-2-cyanoacrylate (2-ECA), n-butyl-2-cyanoacrylate (nBCA) isobutyl-cyanoacrylate (ICA) and 2-octyl-cyanoacrylate (2-OCA). The short-chain forms (2-MCA, 2-ECA) are rarely used due to their rapid degradation and toxic effects; whereas the long-chain forms (nBCA, 2-OCA) are the most widely used in industry and medicine because they provide a strong and rigid bond in contact with tissues [
8]. In fact, having a consistency like that of a liquid gel at room temperature, when it comes into contact with basic substances (such as water, blood, body tissue or moisture) or negatively charged ions, it undergoes an exothermic polymerization that hardens it into a solid adhesive film [
9,
10]. The cyanoacrylate glue used in this work is Glubran 2, a CE-certified Class III surgical medical device for internal and endovascular use [
11,
12]. This device has undergone preclinical and clinical testing to assess its safety. In particular, it has undergone biocompatibility testing, performance testing and animal studies (depending on the application). Biocompatibility tests are trained according to Good Laboratory Practice (GLP; 21 CFR 58) in accordance with International Organization for Standardization (ISO) 10993. Laboratory tests demonstrating safety and efficacy prior to animal studies include the following: cytotoxicity - International Organization for Standardization (ISO10993-5), sensitization and irritation (ISO 10993-10), implantation (ISO 10993-6), pyrogenicity, acute, subchronic, and chronic toxicity (ISO10993-11), hemolysis (ISO 10993-4), genotoxicity (ISO 10993-3). Animal studies for specific applications of Glubran have been conducted on sheep, dogs, rats, mice and pigs. In addition to these tests, as bioadhesives in contact with blood degrade with time, degradation studies and blood-compatibility studies are performed on them [
13].
In particular, in the case of Glubran 2, several models were developed to mimic different clinical situations. For example, the ascending pharyngeal artery in the pig serves as a model for arteriovenous malformations (AVMs). Aneurysms, including aortic aneurysms, have been created in rabbits and pigs and arteriovenous fistulas in dogs [
14].
This device has a high adhesive capacity in a humid environment (viable tissue) with haemostatic, sealing and bacteriostatic (barrier) properties, high elasticity and tensile strength for waterproof and breathable bonding, a low polymerization temperature (45°C) that starts on contact with the tissue (1-2 seconds) and is complete in 60-90 seconds [
15,
16]. It also possesses high biocompatibility and slow biodegradability, does not cause release of toxic products and the minimum use quantity is 1 ml T20 cm
2 . The film formed after application of this glue can be easily punctured by suture needles and the glue when mixed with Lipiodol® can be opacified and its rate of polymerization can be altered and favoring the formation of a less uniform and more flocculent polymer with a gel-like consistency (embolizing agent) [
17]. Glubran 2 is commercially available as ready-to-use disposable applicator devices, formulated as a clear liquid in single-dose bottles of 0.25; 0.50; 1 ml to be stored between 2 and 8°C. Blood vessels that are subjected to Glubran 2 injection are embolized via three mechanisms: (1) cast and thrombus formation [
18,
19], (2) the adhesion to the inner vascular wall [
20], and (3) damage to the vascular endothelium caused by an inflammatory response [
21]. Another device used in the vascular field with hemostatic action is the Arista
TMAH an absorbable topical hemostatic that uses hydrophilic polysaccharide hemosphere (MPH) technology to help control blood loss [
22]. The product is derived from purified vegetable starch and is supplied as a powder substance with a variety of applicators. Starch is an abundant hydrophilic natural biopolymer composed of anhydroglucose units that have hydrophilicity, biodegradability, biocompatibility, and similarity to skin extracellular matrix, making them useful for various biomedical applications. Hydrophilicity and biodegradability are two crucial properties of starch granules that belong to the passive hemostats class and act as a ‘‘molecular sieve’’ by extracting fluids and blood [
23,
24]. Instead, the Arista
TMAH haemostatic activity is activated when, upon meeting the liquid components of the blood, they are absorbed by the polysaccharide hydrogel-hemospheres and are concentrated to form a molecular network (gel) that allows efficient thrombus formation through natural coagulation (
Figure 1). In fact,
in situ gelling polymeric systems having functional groups that can react with functional groups present in tissue, have been found to be adhesive in nature [
25]. This device has been approved by the FDA precisely because it enhances the biological process of coagulation through the formation of a natural haemostatic plug. Also in the case of Arista
TMAH, clinical and preclinical tests to assess its safety are based on biocompatibility tests, performance tests and animal studies. Animal studies are mainly carried out on 6-8 week old Sprague-Dawley rat models in which the surgical site is performed in the abdominal area. Tests showed no signs of inflammation at any time after application of the powder [
26]. The aim of this work was to evaluate the effectiveness and safety of the two devices in the surgical field by differentiating their application based on the pathology treated and the hemostasis mechanism exerted on it.