Semiresorbable biologic hybrid meshes for ventral abdominal hernia repair in potentially contaminated settings: lower risk of recurrence

In case of potential contamination, implantation of synthetic meshes in hernia and abdominal wall surgery is problematic due to a higher risk of mesh infection. As an alternative, a variety of different biologic meshes have been used. However, relevant data comparing outcome after implantation of these meshes are lacking. Between January 2012 and October 2021, biologic meshes were used for reconstruction of the abdominal wall in 71 patients with preoperative or intraoperative abdominal contamination. In this retrospective study, semiresorbable biologic hybrid meshes (BHM) and completely resorbable meshes (CRM) were compared and analyzed using a Castor EDC database. In 28 patients, semiresorbable biologic hybrid meshes were used; in 43 patients, completely resorbable meshes were used. Both groups showed no difference in age, gender, BMI, operation duration, hernia size and Charlson comorbidity index. The risk degree of surgical-site occurrences was graded according to the Ventral Hernia Working Group (VHWG) classification, and the median value was 3 (range 2–4) in the BHM group and 3 (range 2–4) in the CRM group. Hernia recurrence within 24 months after hernia repair was significantly lower in the BHM group (3.6% vs. 28.9%; p = 0.03), while postoperative complication rate, with respect to seromas in need of therapy (61.4% vs. 55.5%, p = 0.43) and operative revision (28.6% vs. 16.3%, p = 0.22) was not different in either group. Biologic hybrid meshes can be used safely in case of possible contamination. BHM seems to reduce the risk of hernia recurrence compared to completely resorbable biologic meshes, but this has to be investigated further.


Introduction
In the surgical treatment of abdominal wall hernias, the use of meshes is recommended for larger hernias, and is associated with a significantly lower rate of hernia recurrence [1][2][3]. However, mesh infections represent a serious complication with a relevant necessity of reintervention and mesh removal, especially in contaminated wound situations [4,5]. While synthetic meshes are commonly used, biologic meshes were invented as an alternative to reduce the risk of superinfection [6][7][8][9]. Since the advantage of biologic compared to synthetic meshes is discussed controversially in the literature [5,[10][11][12][13][14][15], clear guidelines on when to use biologic meshgrafts are lacking. Consequently, the decision about whether or not to use a biologic mesh, and which type depends on the intraoperative assessment of the individual surgeon. Many different types of biologic and biosynthetic meshes are available, most of them completely resorbable [6][7][8]. In our department, in the case of verified or possible wound contamination, we recently changed from using completely resorbable biologic meshes to OviTex ® 2s reinforced 1 3 tissue meshes, consisting of a combination of ovine extracellular matrix and non-resorbable polypropylene fibers. The outcome in this group compared to all other patients with biologic meshgraft hernia repair was analyzed in this study.

Methods
Between January 2012 and October 2021, 71 cases with biologic mesh implantation in the setting of preoperative or intraoperative possible wound contamination were identified. Only patients with reconstruction of the abdominal wall, which included ventral abdominal hernias and abdominal cavity closing after open abdomen situations, were enrolled in this study. Other indications for mesh implantation were excluded. To compare the outcome of the different meshes, the patients were retrospectively separated into a semiresorbable (BHM) and a completely resorbable meshes (CRM) group. The data were stored in a Castor EDC database and analyzed using IBM SPSS statistics 26. Statistical analysis was done using Student's t test in case of normally distributed data, and otherwise the Mann-Whitney U test. The Chi-square test was used, if appropriate, to compare nominal variables. The recurrence-free survival rates were calculated with a Kaplan-Meier analysis and the log-rank method was used to compare these rates between groups. A p value of 0.05 or less was considered statistically significant. The study was approved by the ethics committee of the University of Regensburg, Germany (Nr. 19-1547-101).

Materials
In total, four different types of biologic meshes were used. Three of them were completely resorbable and 1 semiresorbable:

Patient characteristics
Both groups showed no statistical difference in age, gender, BMI, Charlson Comorbidity Index, or hernia size, and only the presence of stomata was significantly higher in the CRM group (p = 0.01) ( Table 1). The median age was 58 years (range 1-82 years) in the BHM group and 57 years (range 0-82 years) in the CRM group. 53.6% of the patients were male in the BHM cohort, and 60.5% in the CRM group. The median BMI was 28.8 kg/m 2 (range 15-41.8 kg/m 2 ) for patients treated with a biologic hybrid mesh compared to 27.5 kg/m 2 (range 13.5-72.6 kg/m 2 ) in the CRM group. Furthermore, a median of 3.5 points (range 0-8 points) were generated using the Charlson Comorbidity Index in the BHM group and 3 points (range 0-10 points) in the CRM group. While all patients had undergone abdominal surgical treatment in the past, the median number of previous operations was 4.5 (range 1-6) in the BHM group and 5 (range 1-6) in the CRM group. The risk degree of surgical-site occurrences according to the VHWG classification indicated a median value of 3 (range 2-4) in the BHM group and 3 (range 2-4) in the CRM group. The median hernia size was 220.7 cm 2 (range 20.7-586.6 cm 2 ) in the BHM group and 107.8 cm 2 (range 0.2-505.5 cm 2 ) in the CRM group. Preoperative wound conditioning, either through negative wound pressure therapy or regular lavage (Table 1), was performed in the BHM group and the CRM group in 42.9% and 37.2% of the cases, respectively (p = 0.64).

Operative items
The median operation time was 162 min (range 51-493 min) in the BHM group and 157 min (range 37-511 min) in the CRM group. The mesh grafts were placed as intraperitoneal onlay mesh (IPOM), sublay, bridging, and onlay in 11 (39.3%),

Laboratory results
In both groups, a notable increase in CRP scores (Fig. 2), white blood cell counts (Fig. 3), and procalcitonin (PCT) (Fig. 4) was seen over the initial 2-3 days after mesh implantation, with no significant differences between the BHM and the CRM group. In the further postoperative course, all three parameters steadily decreased in both groups, but never reached the normal range over the first 14 days.

Discussion
The results of this study suggest that semiresorbable biologic hybrid meshes show a significantly lower hernia recurrence rate (p = 0.03) in a mid-term follow-up period when compared to completely resorbable biologic meshgrafts in potentially contaminated wounds. Comparable results regarding hernia recurrence rates for meshes with non-resorbable components are found in the current literature [5, 9-13, 16, 17]. Although most studies only compare non-resorbable synthetic meshes with different completely resorbable biologic meshes [5,[10][11][12][13], Parker et al. [9] and Timmer et al. [16] as well as the 12 months analysis of the ongoing prospective BRAVO study [17] present low rates of hernia recurrence and surgical-site occurences requiring intervention for biologic hybrid meshes. Confirming the low rate of surgical-site complications in these studies, both groups in our study show a comparable safe use in complex patients and potentially contaminated wound situations. We observed a slightly higher rate of operative revisions without statistical significance in the BHM group (28.6% vs 16.3%), mostly due to wound infections, which is an acceptable level for such complex patients when considering the bigger defect size (220.7 cm 2 vs. 107.8 cm 2 ) and is consistent with the current literature analyzing biologic meshgrafts [5][6][7][8][9]. Moreover, mesh removal was not necessary in either the BHM or CRM group. A further complication seen twice as much without reaching the significance level in the BHM group in our study is the development of postoperative seromas. This is not necessarily related to contamination, but could also be due to an early immunological reaction, which is triggered more intensively by the monofilament polypropylene fibers, and was previously observed in a non-human model for these meshes [18]. This assumption is supported by the low rate of microbiological findings after drainage of these seromas and the similar need of reintervention in both groups. Therefore, the clinical condition of the patient and signs of a systemic infection in combination with raised infection parameters should be evaluated before considering an intervention. There are, of course, some limitations to our study mainly because of the retrospective study design without randomization, which must be considered. Generally, a possible bias in patient selection cannot be completely excluded, although the presence of stomata was the only significant difference in patient characteristics between both groups. Furthermore, an increasing experience of the surgeons due to non-contemporaneous mesh usage is possible and the patient number (28 vs. 43) as well as the follow-up period (16 months vs. 31.5 months) differs in both groups.
Nevertheless, a clear benefit of this study is the comparison of a new semiresorbable biologic hybrid mesh with other kinds of completely resorbable biologic meshes, which is a valuable comparison that has not yet been done before. However, since only ovine biologic hybrid meshes were used in this study, all conclusions must be limited to this type of meshgraft.

Conclusion
In summary, we suggest that semiresorbable biologic hybrid meshes are safe to use in complex patients with possible wound contamination and potentially reduce the risk of hernia recurrence compared to CRM in a mid-term follow-up period. Despite the heterogeneity of the presented retrospective study, our data show actual clinical courses of complex patients. However, for definitive clinical and economic conclusions, further prospective randomized trials and long-term follow-up data are required.
Author contributions MG: participated in research design, data collection, data analysis, and writing of the paper. MJ: participated in data collection and data analysis. HJ: participated in data analysis. HJS: participated in writing of the paper. SMB: participated in research design, and writing of the paper. FWB: participated in research design, data analysis, and writing of the paper.
Funding Open Access funding enabled and organized by Projekt DEAL. A funding grant of 2500 Euro for the Castor EDC data base access was received by TELA Bio. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.

Fig. 2
Both groups show a notable increase in the CRP score within the first 3 days after mesh implantation. Although slowly decreasing afterwards, CRP levels stay elevated over the next several days. No significant difference is seen between groups Fig. 3 Similar to the CRP levels, the white blood cell count also increases until day 3 after the operation, and decreases over the following days. No statistical difference is seen between groups Fig. 4 Shown is the PCT level course over the first 14 days. In the CRM group, the PCT level is higher than in the BHM group until postoperative day 10. Afterwards, the curves begin to align. No significant difference is reached