The objective of this study was to evaluate the mechanical and histological properties of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh (Phasix™ ST) compared to partially absorbable (Ventralight™ ST), fully absorbable (Phasix™), and biologically derived (Strattice™) meshes in a porcine model of ventral hernia repair.
Mechanical testing revealed that sites repaired with coated (Phasix™ ST) or uncoated (Phasix™) versions of the poly-4-hydroxybutyrate technology had similar mesh/repair strength and were both significantly stronger than NAW at 12 and 24 weeks. These results suggest that Phasix™ ST and Phasix™, with associated tissue ingrowth, augmented the strength of the NAW despite partial resorption of mesh fibers comprising these devices. In addition, Phasix™ ST and Phasix™ demonstrated comparable mesh/repair strength to Ventralight™ ST, which suggests that they may provide medium-term mechanical strength comparable to partially absorbable mesh incorporating a permanent polypropylene scaffold. However, it is noteworthy that Ventralight™ ST exhibited significantly greater mesh/repair strength at 24 weeks compared to Phasix™ ST, which may be due to volume differences in PGA fiber content (Phasix™ ST possesses ~40 % less PGA fiber), biomechanical differences between P4HB/polypropylene load-bearing components, and/or partial resorption of P4HB.
Although exhibiting the greatest preimplantation strength of all biomaterials evaluated in this study, biologically derived (Strattice™) mesh/repairs demonstrated 78 % lower mechanical strength relative to preimplantation strength at 12 weeks, indicating a rapid strength decline in vivo. Comparatively, sites repaired with Strattice™ were significantly weaker than sites repaired with the fully absorbable biosynthetic mesh (Phasix™), as early as 12 weeks. These biologically derived scaffold observations are similar to previously reported results by Cavallo et al. that demonstrated 91 % and 96 % lower mechanical strength for biologically derived (Strattice™) mesh/repairs relative to preimplantation strength at 1 and 6 months, respectively [19, 26]. Similarly, Monteiro et al. also showed a 40, 84, and 81 % reduction in mechanical strength for Strattice™ mesh/repairs relative to preimplantation strength at 2, 4, and 6 weeks, respectively [27]. However, it should be noted that in the current study, the strength of Strattice™ mesh/tissue repairs at both 12 and 24 weeks was still approximately 3 times the strength of NAW alone. Clinical studies are required to determine whether this strength profile is compatible with the dynamic load-bearing requirements of the human abdominal wall in specific targeted patient populations.
As demonstrated through mechanical testing in this porcine study, the relatively slow degradation rate of the load-bearing component within Phasix™ ST and Phasix™ (P4HB) may be advantageous in facilitating a more gradual transfer of load from the mesh back to the native tissue compared to biologically derived or rapidly resorbing synthetic biomaterials. Rapid mechanical degradation of biomaterials could result in premature transfer of load back to the native tissue before the repair site has been fully remodeled and strengthened by mature collagen and may ultimately contribute to hernia recurrence rates. Within the Repair of Infected or Contaminated Hernias (RICH) clinical trial (NCT00617357), Itani et al. previously reported 28 % hernia recurrence at 2 years following ventral hernia repair with biologically derived non-cross-linked porcine dermis (Strattice™) in CDC class II to IV patients [28]. Within the Complex Open Bioabsorbable Reconstruction of the Abdominal Wall (COBRA) clinical trial (NCT01325792), Rosen et al. recently reported 17 % hernia recurrence at 2 years following ventral hernia repair with a synthetic fully absorbable mesh (Gore® Bio-A®) in CDC class II to III patients [29]. Additional clinical studies are warranted to determine whether rapid mechanical degradation of the devices evaluated ultimately contributed to the observed hernia recurrence rate and/or whether longer-term fully absorbable biosynthetics could improve upon these results.
The predictable, long-term resorption profile associated with Phasix™ ST and Phasix™ may also be beneficial in protecting these meshes from rapid degradation by collagenases if inadvertently exposed to bacteria during/after implantation. Deeken et al. have shown that Strattice™ is rapidly degraded by collagenases during in vitro studies, leading to a significant loss of mechanical strength, particularly when compared to cross-linked porcine dermis material such as Permacol™ [30]. Additionally, Sahoo et al. have shown that enzymatic degradation of non-cross-linked human acellular dermal matrices leads to a significant decline in mechanical properties and frequently mechanical failure of the material [31]. These results compare well with those of the current study and provide rationale for further evaluation of Phasix™ ST and Phasix™ in future studies with bacterial or collagenase exposure.
Histological analysis of each mesh was performed to provide additional insight into the host response associated with each of the mesh materials evaluated in this study. The results revealed that Phasix™ ST mesh exhibited minimal–mild inflammation, fibrosis, and neovascularization characteristics comparable to Ventralight™ ST and Phasix™. Additionally, these three meshes exhibited similar responses at both 12 and 24 weeks, indicating a stable host tissue response with insignificant changes over time.
In contrast, Strattice™ was associated with significant changes in neovascularization over time. At 12 weeks, neovascularization scores for Strattice™ were significantly lower than scores reported for Phasix™ mesh. However, neovascularization scores for Strattice™ increased significantly between 12 and 24 weeks, reaching levels of neovascularization comparable to the other three mesh types by 24 weeks. Morphological characteristics such as overall surface area may contribute to these temporal differences between materials. The microporous, sheet-like structure inherent in biologically derived scaffolds may slow the overall rate of tissue integration and vascularization compared to the macroporous, monofilament structure of Phasix™ ST and Phasix™, which facilitates rapid integration and neovascularization, similar to traditional and composite ventral hernia repair prosthetics.
Interestingly, Strattice™ was also associated with significantly less inflammation at 24 weeks compared to Phasix™ mesh. This may be explained by the differing resorption profiles associated with these materials. As shown in Fig. 6, Strattice™ was significantly resorbed/remodeled by 24 weeks, while Phasix™ remained largely intact. Thus, the inflammatory response was absent/minimal for Strattice™, but remained an ongoing, mild response for Phasix™.
The results of this study compare well with similar, previously published studies [24, 25, 27, 32]. In 2013, Deeken et al. evaluated Phasix™ in a porcine model of hernia repair at 6, 12, 26, and 52 weeks postimplantation. The results were comparable to the current study and showed that Phasix™-repaired sites were significantly stronger than NAW at all time points with a mild inflammatory response [25]. In another study, Martin et al. evaluated Phasix™ in a porcine model at 8, 16, 32, and 48 weeks postimplantation. Again, the results were comparable to the current study and showed that Phasix™-repaired sites were significantly stronger than NAW at 8 and 16 weeks and comparable to NAW thereafter, with a moderate inflammatory response present at all time points [32]. In a third study, Monteiro et al. evaluated Strattice™ in a porcine model at 2, 4, and 6 weeks postimplantation. These results were also comparable to the results of Strattice™ in the current study and showed a mild inflammatory response with rapid 40, 84, and 81 % decline in mesh strength at 2, 4, and 6 weeks, respectively [27].
There are some limitations associated with the current study that deserve consideration. First, the medium-term implant duration of 24 weeks is limited given the longer-term resorption profile associated with Phasix™ ST and Phasix™ compared to that associated with Strattice™. The results of this study provide an understanding of the short- to medium-term tissue response and mechanical properties associated with these materials. However, future studies should include longer implant durations to more fully characterize the responses associated with these materials after complete resorption of not only the barrier layer, but also the primary load-bearing structural component of the mesh. Additionally, although this study provides important insight using an established large animal model, the impact of mesh resorption on hernia recurrence rates and clinical performance should be addressed in future clinical trials. Furthermore, there are some limitations associated with the T0 and NAW specimens chosen for this study. In future studies, it may be useful to also include a T0 sample of mesh/tissue repair strength immediately after surgical implantation of the mesh over a repaired defect in addition to the T0 mesh-only data acquired here. This type of specimen would provide additional insight into the contribution of the repaired tissue to the strength of the initial mesh/tissue repair prior to mesh resorption or tissue ingrowth. Finally, it should be acknowledged that specimens obtained for histological analysis were taken after the completion of mechanical testing. It is possible that artifacts were created in the tissue specimens due to compression during testing, although no such observations were noted by the pathologist.