META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair.

PURPOSE: The objective was to evaluate the host response, resorption, and strength properties, and to assess the performance in the presence of bacteria for Phasix™ Mesh (Phasix™) and Gore® Bio-A® Tissue Reinforcement (Bio-A®) in preclinical models. METHODS: In a rat model, one mesh (2 × 2 cm) was implanted subcutaneously in n = 60 rats. Animals were euthanized after 2, 4, 8, 12, 16, or 24 weeks (n = 5/mesh/time point), and implant sites were assessed for host inflammatory response and overall fibrotic repair thickness. In a rabbit model, meshes (3.8 cm diameter) were bilaterally implanted in subcutaneous pockets in n = 20 rabbits (n = 10 rabbits/mesh) and inoculated with 108 CFU clinically isolated methicillin-resistant Staphylococcus aureus (MRSA). One mesh type was implanted per animal. Animals were euthanized after 7 days, and implants were assessed for abscess formation, bacterial colonization, and mechanical strength. RESULTS: In the rat study, Phasix™ and Bio-A® exhibited similar biocompatibility, although Bio-A® demonstrated a significantly greater inflammatory response at 4 weeks compared to Phasix™ (p < 0.01). Morphometric analysis demonstrated rapid resorption of Bio-A® implants with initially thicker repair sites at 2, 4, 8, and 12 weeks (p < 0.0001), which transitioned to significantly thinner sites compared to Phasix™ at 16 and 24 weeks (p < 0.0001). In the rabbit bacterial inoculation study, Phasix™ exhibited significantly lower abscess score (p < 0.001) and bacterial colonization (p < 0.01), with significantly greater mechanical strength than Bio-A® (p < 0.001). CONCLUSIONS: Host response, resorption, repair thickness, strength, and bacterial colonization suggest a more stable and favorable outcome for monofilament, macroporous devices such as Phasix™ relative to multifilament, microporous devices such as Bio-A® over time.

Remodeling characteristics and biomechanical properties of a crosslinked versus a non-crosslinked porcine dermis scaffolds in a porcine model of ventral hernia repair.

PURPOSE: The objective of this study was to evaluate the histologic remodeling profile and biomechanical properties of the porcine abdominal wall after repair with HDMI-crosslinked (Permacol(®)) or non-crosslinked (Strattice(®)) porcine dermis in a porcine model of ventral hernia repair. METHODS: Bilateral incisional hernias were created in Yucatan minipigs and repaired after 21 days. The repair site, including mesh and abdominal wall, was harvested after 1, 6, and 12 months and subjected to histologic analysis and uniaxial testing. Native abdominal wall without mesh was also subjected to uniaxial tensile testing. RESULTS: Permacol(®) demonstrated significant improvement over time in every remodeling category except scaffold degradation, while remodeling characteristics of Strattice(®) remained relatively unchanged over time for every category except fibrous encapsulation and neovascularization. However, remodeling scores for Strattice(®) were already significantly higher after just 1 month compared to Permacol(®) in the categories of cellular infiltration, ECM deposition, and neovascularization, providing evidence of earlier remodeling of the non-crosslinked grafts compared to the crosslinked grafts. The tensile strength and stiffness of both crosslinked and non-crosslinked graft-tissue composites were greater than the tensile strength and stiffness of the native porcine abdominal wall in the very early post-operative period (1 month), but there was no difference in tensile strength or stiffness by the end of the study period (12 months). CONCLUSIONS: HDMI collagen crosslinking of porcine dermis scaffolds reduces the early histologic remodeling profile but does not significantly impact the tensile strength or stiffness of the graft-tissue composites in a porcine model of ventral hernia repair.

A comparative study of the remodeling and integration of a novel AuNP-tissue scaffold and commercial tissue scaffolds in a porcine model.

The extracellular matrices of a variety of human and animal tissues have been utilized as scaffold materials for soft tissue applications including hernia repair, dermal grafts, and tendon, ligament, and cartilage reconstruction. While these biological scaffolds are expected to demonstrate superior tissue integration, there is very little evidence documenting the properties and behavior of these materials in vivo. This in vivo study investigated four biological scaffolds: two commercially available (a moderately crosslinked scaffold and a noncrosslinked scaffold) and two novel porcine diaphragm biological scaffolds (one with and one without the incorporation of gold nanoparticles). The scaffolds were implanted in a porcine model and evaluated over 1, 3, and 6 months. The moderately crosslinked scaffolds demonstrated the least cellular infiltration and evidence of fibrosis. The noncrosslinked scaffolds demonstrated the greatest cellular infiltration, but these scaffolds were delaminated and exhibited a rapid loss of integrity. The porcine diaphragm scaffolds with and without nanoparticles showed evidence of tissue remodeling and cellular infiltration, with no evidence of encapsulation. While there were no significant differences in the performance of the two novel scaffolds, the gold nanoparticle scaffold typically exhibited higher cellular infiltration. This study demonstrated the potential biocompatibility of a gold nanoparticle-tissue scaffold.

Comparison of contracture, adhesion, tissue ingrowth, and histologic response characteristics of permanent and absorbable barrier meshes in a porcine model of laparoscopic ventral hernia repair.

PURPOSE: The objective of this study was to determine the mesh contracture, adhesion, tissue ingrowth, and histologic characteristics of a novel absorbable barrier mesh (Ventrio™ ST Hernia Patch) compared to existing permanent (Ventrio™ Hernia Patch) and absorbable barrier meshes (Sepramesh™ IP Composite and PROCEED™ Surgical Mesh). METHODS: Standard laparoscopic technique was utilized to bilaterally implant meshes in 20 female Yorkshire pigs (n = 5 pigs/group). Meshes were fixated to the intact peritoneum with SorbaFix™ absorbable fixation devices. Mesh contracture, adhesion coverage, and adhesion tenacity were evaluated after 4 weeks. T-Peel testing and hematoxylin and eosin (H&E) staining were utilized to assess tissue ingrowth and host response. RESULTS: A significantly greater percent area contracture was demonstrated for PROCEED™ (26.9%) compared to Ventrio™ ST (8.8%), Ventrio™ (14.5%) and Sepramesh™ (9.2%). Ventrio™ ST demonstrated similar adhesion area, tenacity, and tissue ingrowth compared to all other meshes. Histological scoring revealed a comparable host inflammatory response for all meshes, with a few exceptions. A greater number of giant cells were observed in Ventrio™ ST and Sepramesh™ near the multifilament polyglycolic acid (PGA) fibers; a greater number of macrophages were observed in PROCEED™ compared to Ventrio™; and a greater number of neutrophils were observed in PROCEED™, compared to Sepramesh™ (P < 0.05). Focal areas of hemorrhage were also observed on the visceral surface of PROCEED™. CONCLUSIONS: Ventrio™ ST Hernia Patch demonstrated comparable contracture, adhesion, tissue ingrowth, and histologic characteristics compared to existing permanent and absorbable barrier meshes. Host inflammatory and fibrotic responses for all four meshes were minimal and representative of a biocompatible response.

Histologic evaluation of absorbable and non-absorbable barrier coated mesh secured to the peritoneum with fibrin sealant in a New Zealand white rabbit model.

PURPOSE: The purpose of this study is to evaluate the histologic response to fibrin sealant (FS) as an alternative fixation method for laparoscopic ventral hernia repair. METHODS: One non-absorbable barrier mesh (Composix™) and three absorbable barrier meshes (Sepramesh™, Proceed™, and Parietex™ Composite) were used for the study, with uncoated macroporous polypropylene mesh (ProLite Ultra™) as the control. Three methods of fixation were used: #0-polypropylene suture + FS (ARTISS™, Baxter Healthcare Corp.), FS alone (ARTISS™), or tacks alone (n = 10 for each group). Two pieces of mesh (of dimensions 4 × 4-cm) were secured intraperitoneally in 75 New Zealand white rabbits. After 8 weeks, hematoxylin and eosin (H&E)-stained specimens were evaluated for host tissue response. Statistical significance (P < 0.05) was determined using a one-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) post hoc test. RESULTS: Composix™ with FS only showed significantly greater cellular infiltration than with suture + FS (P = 0.0007), Proceed™ with FS only had significantly greater neovascularization than with suture + FS (P = 0.0172), and ProLite Ultra™ with suture + FS had significantly greater neovascularization than with tacks only (P = 0.046). Differences due to mesh type showed that Composix™ exhibited less extensive cellular infiltration (P ≤ 0.0032), extracellular matrix (ECM) deposition, and neovascularization, and demonstrated less inflammatory cells and more fibroblasts compared to the other meshes (P < 0.05). CONCLUSIONS: FS did not have a significant histologic effect compared to tacks when utilized for the fixation of mesh to the peritoneum of New Zealand White rabbits. However, the mesh type did have a significant histologic effect. The permanent barrier mesh (Composix™) was associated with less histologic incorporation than absorbable barrier and macroporous meshes, as evidenced by lower levels of cellular infiltration, ECM deposition, and neovascularization, independent of the fixation method used.

Histologic and biomechanical evaluation of a novel macroporous polytetrafluoroethylene knit mesh compared to lightweight and heavyweight polypropylene mesh in a porcine model of ventral incisional hernia repair.

PURPOSE: To evaluate the biocompatibility of heavyweight polypropylene (HWPP), lightweight polypropylene (LWPP), and monofilament knit polytetrafluoroethylene (mkPTFE) mesh by comparing biomechanics and histologic response at 1, 3, and 5 months in a porcine model of incisional hernia repair. METHODS: Bilateral full-thickness abdominal wall defects measuring 4 cm in length were created in 27 Yucatan minipigs. Twenty-one days after hernia creation, animals underwent bilateral preperitoneal ventral hernia repair with 8 × 10 cm pieces of mesh. Repairs were randomized to Bard(®)Mesh (HWPP, Bard/Davol, http://www.davol.com), ULTRAPRO(®) (LWPP, Ethicon, http://www.ethicon.com), and GORE(®)INFINIT Mesh (mkPTFE, Gore & Associates, http://www.gore.com). Nine animals were sacrificed at each timepoint (1, 3, and 5 months). At harvest, a 3 × 4 cm sample of mesh and incorporated tissue was taken from the center of the implant site and subjected to uniaxial tensile testing at a rate of 0.42 mm/s. The maximum force (N) and tensile strength (N/cm) were measured with a tensiometer, and stiffness (N/mm) was calculated from the slope of the force-versus-displacement curve. Adjacent sections of tissue were stained with hematoxylin and eosin (H&E) and analyzed for inflammation, fibrosis, and tissue ingrowth. Data are reported as mean ± SEM. Statistical significance (P < 0.05) was determined using a two-way ANOVA and Bonferroni post-test. RESULTS: No significant difference in maximum force was detected between meshes at any of the time points (P > 0.05 for all comparisons). However, for each mesh type, the maximum strength at 5 months was significantly lower than that at 1 month (P < 0.05). No significant difference in stiffness was detected between the mesh types or between timepoints (P > 0.05 for all comparisons). No significant differences with regard to inflammation, fibrosis, or tissue ingrowth were detected between mesh types at any time point (P > 0.09 for all comparisons). However, over time, inflammation decreased significantly for all mesh types (P < 0.001) and tissue ingrowth reached a slight peak between 1 and 3 months (P = 0.001) but did not significantly change thereafter (P > 0.09). CONCLUSIONS: The maximum tensile strength of mesh in the abdominal wall decreased over time for HWPP, LWPP, and mkPTFE mesh materials alike. This trend may actually reflect inability to adequately grip specimens at later time points rather than any mesh-specific trend. Histologically, inflammation decreased with time (P = 0.000), and tissue ingrowth increased (P = 0.019) for all meshes. No specific trends were observed between the polypropylene meshes and the monofilament knit PTFE, suggesting that this novel construction may be a suitable alternative to existing polypropylene meshes.

Method of preparing a decellularized porcine tendon using tributyl phosphate.

Extracellular matrix (ECM) materials are currently utilized for soft tissue repair applications such as vascular grafts, tendon reconstruction, and hernia repair. These materials are derived from tissues such as human dermis and porcine small intestine submucosa, which must be rendered acellular to prevent disease transmission and decrease the risk of an immune response. The ideal decellularization technique removes cells and cellular remnants, but leaves the original collagen architecture intact. The tissue utilized in this study was the central tendon of the porcine diaphragm, which had not been previously investigated for soft tissue repair. Several treatments were investigated during this study including peracetic acid, TritonX-100, sodium dodecyl sulfate, and tri(n-butyl) phosphate (TnBP). Of the decellularization treatments investigated, only 1% TnBP was effective in removing cell nuclei while leaving the structure and composition of the tissue intact. Overall, the resulting acellular tissue scaffold retained the ECM composition, strength, resistance to enzymatic degradation, and biocompatibility of the original tissue, making 1% TnBP an acceptable decellularization treatment for porcine diaphragm tendon.

Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

PURPOSE: Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. METHODS: Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. RESULTS: There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. CONCLUSIONS: While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

Assessment of the biocompatibility of two novel, bionanocomposite scaffolds in a rodent model.

Two novel, bionanocomposite scaffolds were evaluated in a rodent model over the course of three months to determine whether these scaffolds possessed adequate biocompatibility characteristics to warrant further evaluation as possible tissue reconstruction scaffolds. These bionanocomposite scaffolds were comprised of amine-functionalized gold nanoparticles (AuNP) or silicon carbide nanowires (SiCNW) crosslinked to an acellular porcine diaphragm tendon. It was hypothesized that the addition of nanomaterials to the porcine tendon would also improve its biocompatibility by imparting a nanostructured surface. As early as seven days after implantation, both types of bionanocomposite scaffolds displayed evidence of granulation tissue and the beginning of scaffold remodeling with new collagen deposited by the host, and by ninety-seven days the bionanocomposite scaffolds were completely remodeled with no evidence of any adverse host tissue reaction or scar tissue formation. The AuNP bionanocomposite scaffolds exhibited accelerated scaffold remodeling compared to the SiCNW scaffolds.

Evaluation of fenestrated and non-fenestrated biologic grafts in a porcine model of mature ventral incisional hernia repair.

INTRODUCTION: The purpose of this study is to compare the tissue incorporation of a novel fenestrated and non-fenestrated crosslinked porcine dermal matrix (CPDM) (CollaMend™, Davol Inc., Warwick, RI) in a porcine model of ventral hernia repair. METHODS: Bilateral abdominal wall defects were created in 12 Yucatan minipigs and repaired with a preperitoneal or intraperitoneal technique 21 days after hernia creation. Animals were randomized to fenestrated or non-fenestrated CPDM for n = 6 pieces of each graft in the preperitoneal or intraperitoneal location. All animals were sacrificed at 1 month. Adhesion characteristics and graft contraction/growth were measured by the Garrard adhesion grading scale and transparent grid overlay. Histological analysis of hematoxylin and eosin (H&E)-stained slides was performed to assess graft incorporation. Tissue incorporation strength was measured by a T-peel tensile test. The strength of explanted CPDM alone and de novo CPDM was measured by a uniaxial tensile test using a tensiometer (Instron, Norwood, MA) at a displacement rate of 0.42 mm/s. Statistical significance (P < 0.05) was determined for histological analysis using a Kruskal-Wallis non-parametric test with a Bonferroni correction, and for all other analyses using a two-way analysis of variance (ANOVA) with a Bonferroni post-test or a Kruskal-Wallis non-parametric test with a Dunn's post-test. RESULTS: Intraperitoneal placement of fenestrated CPDM resulted in a significantly higher area of adhesions and adhesion score compared to the preperitoneal placement of fenestrated CPDM (P < 0.05). For both preperitoneal and intraperitoneal placement, histological findings demonstrated greater incorporation of the graft due to the fenestrations. No significant differences were detected in the uniaxial tensile strengths of the graft materials alone, either due to the graft type (non-fenestrated vs. fenestrated) or due to the placement location (preperitoneal vs. intraperitoneal). The incorporation strength (T-peel force) was significantly greater for fenestrated compared to non-fenestrated CPDM when placed in the preperitoneal location (P < 0.01). The incorporation strength was also significantly greater for fenestrated CPDM placed in the preperitoneal location compared to fenestrated CPDM placed in the intraperitoneal location (P < 0.05). CONCLUSIONS: Fenestrations in CPDM result in greater tissue incorporation strength and lower adhesion area and score when placed in the preperitoneal location. Fenestrations in CPDM allow for greater tissue incorporation without accelerating graft degradation. Fenestrations may be placed in CPDM while still allowing adequate graft strength for intraperitoneal and preperitoneal hernia repairs at 1 month in a porcine model.

Evaluation of acute fixation strength of absorbable and nonabsorbable barrier coated mesh secured with fibrin sealant.

INTRODUCTION: The purpose of this study was to evaluate the acute fixation strength of fibrin sealant as an alternative fixation method for laparoscopic ventral hernia repair (LVHR) when utilized with absorbable and nonabsorbable barrier meshes. METHODS: Representative mesh types for LVHR included one nonabsorbable barrier mesh (Bard Composix) and three absorbable barrier meshes (Sepramesh, Proceed, and Parietex Composite Mesh). Macroporous polypropylene mesh (Prolite Ultra) served as a control. An associated pilot study demonstrated that acute fixation was not achieved with C-Qur or Dualmesh, thus these meshes were not subjected to further analysis. Two fibrin sealants varying in thrombin concentration (TISSEEL 500 IU/ml or ARTISS 4 IU/ml) were each utilized to secure a 3 x 4 cm piece of mesh to the peritoneal surface of harvested abdominal wall from New Zealand white rabbits. Ten samples were prepared for each mesh and fibrin sealant combination. The resulting mesh-tissue interface (3 x 3 cm) underwent lap shear testing at a rate of 0.42 mm/s using a tensiometer (Instron 5542, Norwood, MA). The maximum load sustained by the construct was recorded as the acute fixation strength in units of Newtons (N). Data are given as means +/- SEM. Statistical significance (P < 0.05) was determined using a two-way ANOVA and Bonferroni post-test. RESULTS: There was no significant difference (P > 0.05) in the acute fixation strength achieved by ARTISS versus TISSEEL with Composix, Sepramesh, Proceed, and Parietex Composite Mesh. However, Prolite Ultra fixed with ARTISS (7.099 +/- 1.01 N) had a significantly higher tensile strength (P < 0.001) than Prolite Ultra fixed with TISSEEL (3.405 +/- 0.72 N). Among meshes fixed with TISSEEL, Parietex Composite (3.936 +/- 0.73 N) was significantly stronger than Sepramesh (1.760 +/- 0.33 N) (P < 0.05). CONCLUSIONS: Acute fixation strength is equivalent for TISSEEL and ARTISS fibrin sealants for selected nonabsorbable (Composix) and absorbable barrier-coated (Sepramesh, Proceed, and Parietex Composite Mesh) meshes. Previous evaluations in this model indicated fibrin sealant alone did not appear to be a suitable method of fixation with C-Qur or DualMesh against the peritoneum. Long-term evaluation is needed to evaluate the efficacy of this method of fixation using absorbable and nonabsorbable barrier-coated meshes in a model of LVHR.