A Narrative Review on Polypropylene Mesh Complications in Inguinal Hernia Repair - is Titanized Mesh an Option?

Introduction: Since the introduction of mesh in Inguinal Hernia Repair (IHR) the recurrence rate was lowered. Instead, postoperative pain which may be related to mesh side effects e.g. fibrosis, foreign body reaction, erosion and migration, and infection, has been recognized as the relevant outcome factor. The long-term effects of mesh and composite mesh need to be analyzed. Methods: Pubmed, google scholar search using the search terms: polypropylene mesh, titanized mesh, TiMesh ® ; about polypropylene mesh the following terms: adhesion, erosion, infection, shrinkage, migration, seroma, degradation, pain; biocompatibility, foreign body reaction. Also, a bibliography of relevant articles and product-related information was searched. Results: Mesh properties are determined by tensile strength, pore size, weight, reactivity and biocompatibility, elasticity, constitution, and shrinkage. PolyPropylene Mesh (PP) is associated with actual and long-term complications more


Introduction
The use of polypropylene mesh for hernia repair has been published by Usher for the first time [1]. The EU trialist collaboration found that mesh is superior to suture technique in inguinal hernia repair about pain and recurrence [2]. However, mesh and fibrosis turned out to be responsible for pain and other disturbances. Contrary to the manufacturer's disclosures, synthetic materials polypropylene mesh is not without disadvantages and may cause complications [3]. In a report by Anna Collinson and Jessica, Fürst BBC reported on 26th September 2018 that hernia mesh complications affect more than 100,000 patients (complication rate 12-30%) during the last six years before the report in England. Up to 170,000 people who had hernia mesh implants in England over six years could face complications due to BBC's Victoria Derbyshire program [4]. According to this program, many types of hernia mesh implants are being used with little or no clinical evidence [5]. The lightweight mesh may be associated with less chronic pain but an increase in inguinal hernia recurrence [6]. The selection of the mesh depends on the patient's characteristics (age, underlying disease, defect size, preoperative pain). The surgeon should know about mesh properties that are relevant for the success of implantation and for avoiding complications related to mesh: tensile strength, pore size, weight, reactivity and biocompatibility, elasticity, constitution (monofilament, multifilament, patches), and shrinkage. Most complications in inguinal hernia repair with PP mesh are related to the mesh properties. Complications of meshes are infection, adhesion, erosion, shrinkage; migration; seroma, degradation, pain, and recurrence. There is a search for mesh that reduces the risk of complication. Titanized mesh demonstrated improvement in patient reactions to the implanted mesh.

Materials and Methods
Pubmed, google scholar search using the search terms: polypropylene mesh, titanized mesh, TiMesh ® ; about polypropylene mesh the following terms: adhesion, erosion, infection, shrinkage, migration, seroma, degradation, pain; biocompatibility, foreign body reaction. Also bibliogr,aphy of relevant articles and productrelated information was searched.

Mesh Properties
Mesh properties are determined by tensile strength, pore size, weight, reactivity and biocompatibility, elasticity, constitution, and shrinkage [7].

Tensile Strength
Coughing and jumping generate maximum intra-abdominal pressure (170 mmHg; 32 N/cm), which makes it obvious that the tensile strength of meshes (100 N/cm) may not be advantageous [8].

Pore Size
The pore size is important for soft tissue ingrowth. Above 75um it allows infiltration by macrophages, fibroblasts, blood vessels, and collagen. This may help to avoid granuloma bridging and encapsulation. A scar plate formation in meshes with small pores leads to reduced flexibility [9].

Weight
The weight of the mesh depends on the weight of the polymer and the amount of material (Filament, pore size). Heavyweight Mesh (HWM) weighs 100 g/m, and Lightweight Mesh (LWM) typically 33g/m [10]. Reduced mesh material and decreased surface by large pores in LWM are responsible for less foreign body reaction [11]. According to a meta-analysis, LWM reduces pain and feeling of foreign body in Lichtenstein Inguinal Hernia Repair (IHR) [12]. However, LWM in the mesh plug technique may not induce less chronic pain [13]. LWM may also not cause an increased risk of recurrence in IHR compared to HWM [14]. HWM should be used in laparo-endoscopic repairs of direct or large inguinal hernias to reduce recurrence rates according to a meta-analysis by Bakker, et al. (2021). LWM provides no benefit in indirect hernias [15]. In a systematic review, HWM had a distinctive advantage over LWM in recurrence in laparoscopic IHR with equivalent outcomes in complications (postoperative pain, seroma, foreign body sensation, infection, numbness) [16].

Reactivity/Biocompatibility
The mesh material, e.g. Polypropylene (PP), is physically and chemically [17] inert, stable, non-immunogenic, and non-toxic but it may induce a foreign body reaction involving inflammation, fibrosis, calcification, thrombosis, and granuloma. The amount of material (Filament and pore size) is relevant for the reaction. Mesh may influence the collagen composition delaying the replacement of type III collagen by the stronger type I collagen [18]. The intensity of oxidative stress seems to be strongly related to the amount of implanted polypropylene [

Constitution
Constitution is formed by multifilament and monofilament fibers with multifilament fibers increasing the risk of infection [28].

Shrinkage
PP mesh may cause an inflammatory response, foreign body reaction, and scar tissue, which may be responsible for shrinkage [29]. Prosthetic meshes are not inert as claimed to be and can expand as well as shrink [30]. Shrinkage depends on both mesh properties-small pores producing scar tissue -and the anchoring device [31]. Mesh characteristics should be considered when choosing the mesh for IHR [32].

Complications of Anterior Inguinal Hernia Repair
In a meta-analysis, there was no difference between Prolene Hernia System ® (PHS) and Lichtenstein IHR for recurrence, chronic pain, operating time, composite complication, and surgical reintervention [33]. Meta-analysis showed that Mesh-Plug Repair (MPR) requires a shorter operation time than Lichtenstein herniorrhaphy, and there is no significant difference in postoperative complications or recurrence rate [34]. This metaanalysis indicates that MPR mesh plug repair and PHS ® seem comparable to LR Lichtenstein repair in terms of recurrence, chronic pain, time to return to work, inguinal paresthesia, testicular and scrotal problems, hematoma, seroma and wound infection. MPR and PHS ® seem comparable in terms of recurrence, chronic pain, and wound infection [35].

Complications of Laparoscopic Inguinal Hernia Repair
A meta-analysis comparing Lichtenstein and TAPP indicates that the complication rate and outcome of both procedures are comparable. TAPP operation demonstrated only one advantage over Lichtenstein operation with significantly less chronic inguinal pain postoperatively [36]. TAPP was associated with a lower seroma rate, and TEP was associated with a lower edema rate according to a meta-analysis [37]. There was less early pain and fewer analgesics after TEP repair, compared to Lichtenstein repair with similar infection rates in this Randomized Controlled Trial (RCT) [38].

Mesh and Vessels
Mesh-induced inflammation and fibrosis may influence blood flow in arteries and veins [39]. Mesh fibrosis may not affect testicular flow [40]. However, dysejaculation and pain-related impairment of activity may be a complication of laparoscopic inguinal herniorrhaphy [41]. Tailored neurectomy, funicular release, and or mesh removal may be helpful [42]. In a recent systematic review, it has been stated that hernia repair with meshopen or laparoscopic-does not affect male fertility [43].

Adhesion
All meshes induce adhesion. Absorption is reduced by ischemia, inflammation, and the foreign body. Pore size, filament structure, and the surface of the mesh structure are decisive in how much adhesion is produced when the mesh is placed in the vicinity of the bowel. Microporous structure at the side of the bowel and additional surface [58] in composite meshes provide a temporary barrier against adhesion. However, the absorbable coatings may be degraded in the short term [59].

Erosion
Mesh erosion into intra-abdominal organs [60-62] is a serious long-term complication, which may be clinically apparent with unspecific symptoms. Mesh migration, adhesion, and formation of granulation tissue are relevant mechanisms [63] that may lead to enterocutaneous fistula [64]. Treatment of mesh erosion may be possible by a laparoscopic approach [65]. It is important to completely close the peritoneum when placing the mesh [66]. 23% of patients in a case series experienced early intestinal erosions occurring during the first 6 postoperative months while the remaining 67% occurred after 6 months. Patients presented most commonly with symptoms of acute obstruction followed by a palpable inguinal mass. The late presentation group after six months exhibited significantly more cases of mesh erosion when compared to the early presentation group. Early cases were more often associated with mesh fixation material erosion and symptoms of acute intestinal obstruction. An open primary procedure was more common in late cases while the early presentation was linked to laparoscopic procedures. Bowel resection was more frequently required in late cases [67].

Mesh Fixation
A self-gripping mesh for hernia repair may result in less pain in the early postoperative phase but chronic post herniorrhaphy pain is not affected. Recurrence rates may be a potential disadvantage [78]. Mesh fixation with glue compared with sutures in Lichtenstein repair inguinal hernia is faster and less painful, without an increase in terms of recurrence rates in the long term [79] The self-gripping mesh and sutured mesh have a similar incidence of chronic postoperative inguinal pain, recurrence, and foreign body sensation. The main advantage of the self-gripping mesh is the consistently significantly reduced operation time [80]. Early and late recurrence was comparable between glue and suture fixation in open Lichtenstein IHR patients. Glue fixation had a shorter operating time and lower hematoma formation than suture fixation. Chronic pain and seroma formation were comparable [81]. In PP HWM or LWM, neither mechanical nor glue fixation improves the outcome of laparoscopic IHR. In HWM non fixation and LWM, fibrin glue fixation has been recommended [82]. There remains no superiority in terms of mesh fixation; the choice of fixation remains with the surgeon's expertise and the patient's preference [83].

Recurrence
The rate of recurrence has been reduced by the use of mesh. However, there are reports of recurrence after mesh inguinal hernia repair (13% of all herniorrhaphies worldwide). In most instances, the cause of recurrence is not the type of mesh, but inadequate fixation and underestimation of mesh shrinkage as the recurrent hernia occurs at the edge of the meshes (O'Dwyer). Patient risk factors are higher BMI, smoking, diabetes, and postoperative surgical site infections. Surgical risk factors are surgeon's experience, mesh with sufficient overlap, and surgical technique. Type of mesh and fixation of mesh were not significant factors for recurrence [84,85].

Pain
Although the tension-free technique of mesh inguinal hernia has been associated with less postoperative pain, Foreign Body Reaction (FBR) including nerve fibers and fascicles, neuromas at the interface of mesh and soft tissue suggest the destruction of nerves may be responsible for pain in IHR. Mesh with small pores induce a greater FBR leading to higher rates of chronic pain [86]. Despite the popularity and outcome of mesh repair persistent postoperative pain still occurs and may become more evident with the interest in laparoscopic hernia repair [87]. Removal of a meshoma must be considered as success rates are optimized following these measures [88]. The choice of the mesh or fixation method did not affect the overall long-term outcome, pain, or recurrence of the hernia. Less penetrating fixation (Glue or self-gripping mesh) is a safe option for the fixation of mesh in Lichtenstein hernia repair [

Conclusion
Polypropylene mesh has been successful in inguinal hernia repair for decades. However, in recent years complications of PP became evident in scientific reports and the public. Complications seem to be related to the material and structure of the mesh but also to the surgeon's expertise and patient's characteristics. It became evident that more complications appear long-term. The true rate of complications could be higher. There are a few clinical reports on titanium-coated mesh (TiMesh) in TAPP and TEP inguinal hernia repair. Experience with TiMesh in laparoscopic procedures long-term and in open IHR is missing. Especially about the longterm effects of coating PP with titanium we need to have a better understanding of the interaction of soft tissue and mesh. There are promising results of pure titanium mesh which need to be confirmed in further controlled clinical studies.