Impact of different fibrin glue application methods on inguinal hernia mesh fixation capability

The use of fibrin glue for inguinal hernia mesh fixation has been suggested to be effective in preventing hematomas and reducing postoperative pain compared to tacks and sutures.. The effect of fibrin glue can vary significantly based on the device used. This study assessed the efficacy of fibrin glue based on the type of devices used in an ex vivo system. The rabbit’s abdominal wall was trimmed to a size of 3.0 × 6.0 cm and was secured at the edges with metal fixtures. To measure the maximum tensile strength at the point of adhesion failure, the hernia mesh was fixed to the rabbit’s abdominal wall using fibrin glue in a 2 cm square area, left for 3 min, and then pulled at a speed of 50 cm/min. The test was conducted 10 times for each group. The median (minimum–maximum) tensile strength values using the spraying, two-liquid mixing, and sequential layering methods were 3.58 (1.99–4.95), 0.51 (0.27–1.89), and 1.32 (0.63–1.66) N, respectively. The spraying method had predominantly higher tensile strength values than the two-liquid mixing and sequential layering methods (P < 0.01). In conclusion, in hernia mesh fixation, the spraying method can be adopted to achieve appropriate adhesive effects.


Test 1: Methods of fibrin glue application for comparing mesh fixation effects
The abdominal walls were trimmed to a size of 3.0 × 6.0 cm and fixed at the edges with metal fixtures on a base.The hernia mesh (TiLENE® Mesh extralight, pfm medical titanium gmbh, Nürnberg, Germany) was trimmed to a size of 2 × 4 cm, and a loop for traction was attached to one of the ends.Half of the trimmed hernia mesh (2 cm square) closely adhered to the abdominal wall.Fibrin glue (BOLHEAL®, KM Biologics Co., Ltd., Kumamoto Japan) was applied to fix the mesh.The fibrin glue comprises two solutions (fibrinogen and thrombin).Further, 0.4 mL of each solution was used and applied using the spraying, two-liquid mixing, and sequential layering methods (Movie 1).Compressed gas or nongas types could be used in the spraying method.In this study, the nongas-type spray was selected.After 3 min of rest post-application, the mesh was pulled at a speed of 50 cm/ min using a speed controller (Model-2257, Aikoh Engineering Co., Ltd., Osaka, Japan).The pulling method and its speed were based on ASTM F2458-05 (2015) 25 .The maximum tensile strength at the point of adhesion failure was measured with a strength measurer (Model-9500, Aikoh Engineering Co., Ltd., Osaka, Japan) and recorded (Fig. 1).All tests were conducted 10 times each group.

Test 2: Effect of different types of non-heavyweight mesh on adhesive strength
In addition to TiLENE® Mesh extralight, 3DMaxTM Light Mesh (BD, Warwick, Rhode Island, the United States), BARD® Soft Mesh (BD, Warwick, Rhode Island, the United States), and ParietexTM Anatomical Mesh (Medtronic plc, Minneapolis, Minnesota, the United States) were used in the same procedure as in Study 1 (Fig. 2).The spraying method using fibrin glue was adopted in this study because it had the highest adhesive strength based on the preliminary test results.All tests were conducted 10 times each group.www.nature.com/scientificreports/

Statistical analysis
In this test, the Mann-Whitney U test was used to identify significant differences.Preliminary studies showed that 10 experiments were adequate for identifying differences between the spraying, two-liquid mixing and sequential layering methods in Test 1. Statistical analysis in Test 2 was performed in an exploratory manner.
Results yielding two-tailed p-values of < 0.05 were considered significant.All statistical analyses were performed using the EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan) 26 .
In the comparison of ParietexTM Anatomical Mesh with TiLENE® Mesh extralight and 3DMaxTM Light Mesh, it was found to have a median strength of approximately 1 N lower.However, after performing exploratory significance tests, no significant differences were detected under the conditions set, with p-values of 0.123 and 0.089, respectively.

Discussion
The use of a spray device for fibrin glue application in hernia mesh fixation can enhance adhesive effects.This finding is in accordance with that of previous reports from other fields [22][23][24] , and it reconfirms the efficacy of spraying devices.The use of spraying devices also significantly reduces solution dripping when applied to slopes 24 , which is economical because it prevents fibrin glue from flowing down to unintended areas.Several studies on Figure 3.Effect of different fibrin glue application methods on mesh fixation.The spray method had predominantly higher values than the two-liquid mixing method and sequential layering method (P < 0.01).
hernia mesh fixation with fibrin glue, including clinical and nonclinical ones, have been conducted.However, most of these studies did not specify the device used in fibrin glue application.As shown in this study, the type of device and procedure used for applying fibrin glue should be clearly specified.Unified tests on the use of fibrin glue application devices and procedures can reveal various results, potentially altering the current understanding derived from previous basic, nonclinical, and clinical research.There are two types of spray for fibrin glue.That is, one uses compressed gas, and the other utilizes a non-gas type.However, the difference in adhesive strength between the two is negligible 22 .However, caution should be taken when using compressed gas sprays in laparoscopic surgery because of the risk of gas embolism.An updated guideline on the risk of gas embolism associated with the use of fibrin glue spray was issued by the British government in 2014 27 .This guideline specifies the maximum pressure of the gas used and the minimum distance from the tissue.Further, it states that CO 2 gas should be used for laparoscopic surgery.Experiments with pigs have reported that the spray can be safely utilized by opening the trocar valve to limit gas pressure and distance 28,29 .However, the use of compressed gas sprays should not be taken lightly, as the risk management of gas embolism is completely up to the user, except for sprays equipped with a mechanism to release the gas.Non-gas end-type sprays are not associated with a risk of gas embolism; thus, they can be used without concerns.Moreover, the selection of mesh used in conjunction with fibrin glue was also an important factor.When fibrin glue is used for fixation, the use of a lightweight mesh with larger pores leads to a higher adhesive strength in 14 .Clinically, it reduces the consumption of analgesics for managing postoperative pain 30 .Based on these results, heavyweight meshes were preemptively excluded from this study.The four types of meshes adopted in this trial were selected with consideration of their compatibility.Thus, they have a good adhesion.However, Parietex™ Anatomical Mesh may have a slightly different adhesive strength from the other three types.That is, it is somewhat heavier and less elastic than the other three types, which might have affected compliance with the stretched rabbit abdominal wall during traction in this test.If the mesh is fixed with fibrin glue, an appropriate type of mesh should be utilized 14,21,30 , and this should be considered when optimizing the techniques.
Mesh-based hernia repair surgery is a standard procedure.Conversely, various studies on the method used for mesh fixation, including nonfixation, have been performed.As for non-fixation, it appears acceptable in many cases for endoscopic mesh placement.However, there are still instances where fixation is necessary, such as in large M3 type hernias, as outlined in the guidelines by the HerniaSurge Group 7 .Moreover, racial differences, as discussed in the introduction, may influence the efficacy of fixation.Compared with the tack-based fixation methods, the use of fibrin glue for mesh fixation is advantageous because it does not add further invasiveness to the body.Compared with endoscopic tack fixation, fibrin glue is cheaper.Moreover, in terms of postoperative management (administration of analgesics), the cost-efficacy of fibrin is higher, as shown in previous studies 11,31 .Even for groin incisions, fibrin glue is more expensive than sutures.However, when considering the reduction in surgical time, length of hospital stay, and cost of painkillers, the difference is negligible 2 .
Thus, several studies have shown that mesh fixation with fibrin glue has its advantages in cases requiring mesh fixation..However, as indicated in the respective guidelines 7,32,33 , it is not yet considered an optimal method for mesh fixation.A meta-analysis has shown no significant difference in terms of recurrence rates between tacks and sutures 1,5,9 .However, a comparison among the reports regarding the recurrence rate in laparoscopic mesh fixation with fibrin glue reveals considerable variation,, ranging from 0 to 13.6% 8 .Thus, clinical trials have different results.However, if all trials have used fibrin glue with an optimal application method, namely, the spraying technique, the results might have been different.Several factors are associated with the recurrence of inguinal hernia 34,35 .However, a secure mesh fixation should be ensured to prevent recurrence.To achieve a stable adhesive strength, the type of device for applying fibrin glue is important, as reconfirmed in this study.However, this was an ex vivo study using abdominal walls resected from rabbits.Therefore, future clinical trials should compare the advantages of the spraying method versus other methods in mesh fixation.

Conclusions
The effects of fibrin glue vary significantly based on the method used.In inguinal hernia mesh fixation, the spraying method can be adopted to achieve appropriate adhesive effects.Further, when selecting a non-heavyweight mesh with excellent hydrophilicity and large pores, fibrin glue fixation with the spraying method can have stable adhesive effects.

Figure 1 .
Figure 1.Tensile strength testing system.(a) The abdominal wall, extracted from a rabbit, was clamped onto a metal plate.A 2 cm square area, which is half of the trimmed hernia mesh measuring 4 × 2 cm, was fixed to the abdominal wall using fibrin glue.After a 3-min rest, mechanical traction was applied horizontally to measure the maximum tensile strength until adhesion fails.(b) Image of the actual testing system.

Figure 4 .
Figure 4. Result of fixing a nonheavy weight mesh using the fibrin glue spray method.(n = 10).