Dataset Information

Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model.

ABSTRACT: More than a century has passed since the first surgical mesh for hernia repair was developed, and, to date, this is still the most widely used method despite the great number of complications it poses. The purpose of this study was to combine stem cell therapy and laparoscopy for the treatment of congenital hernia in a swine animal model. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were seeded on polypropylene surgical meshes using a fibrin sealant solution as a vehicle. Meshes with (cell group) or without (control group) MSCs were implanted through laparoscopy in Large White pigs with congenital abdominal hernia after the approximation of hernia borders (implantation day). A successive laparoscopic biopsy of the mesh and its surrounding tissues was performed a week after implantation, and surgical meshes were excised a month after implantation. Ultrasonography was used to measure hernia sizes. Flow cytometry, histological, and gene expression analyses of the biopsy and necropsy samples were performed. The fibrin sealant solution was easy to prepare and preserved the viability of MSCs in the surgical meshes. Ultrasonography demonstrated a significant reduction in hernia size 1 week after implantation in the cell group relative to that on the day of implantation (p < 0.05). Flow cytometry of the mesh-infiltrated cells showed a non-significant increase of M2 macrophages when the cell group was compared with the control group 1 week after implantation. A significant decrease in the gene expression of VEGF and a significant increase in TNF expression were determined in the cell group 1 month after implantation compared with gene expressions in the control group (p < 0.05). Here, we propose an easy and feasible method to combine stem cell therapy and minimally invasive surgical techniques for hernia repair. In this study, stem cell therapy did not show a great immunomodulatory or regenerative effect in overcoming hernia-related complications. However, our clinically relevant animal model with congenital hernia closely resembles the clinical human condition. Further studies should be focused on this valuable animal model to evaluate stem cell therapies in hernia surgery.

SUBMITTER: Marinaro F

PROVIDER: S-EPMC7546355 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model.

Marinaro Federica F Casado Javier G JG Blázquez Rebeca R Brun Mauricio Veloso MV Marcos Ricardo R Santos Marta M Duque Francisco Javier FJ López Esther E Álvarez Verónica V Usón Alejandra A Sánchez-Margallo Francisco Miguel FM

Frontiers in pharmacology 20200925

More than a century has passed since the first surgical mesh for hernia repair was developed, and, to date, this is still the most widely used method despite the great number of complications it poses. The purpose of this study was to combine stem cell therapy and laparoscopy for the treatment of congenital hernia in a swine animal model. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were seeded on polypropylene surgical meshes using a fibrin sealant solution as a vehicle. Meshes wit ...[more]

PMID: 33101010

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Project description:BackgroundIt is an undisputable fact that meshes have become standard for repair of abdominal wall hernias. Whereas in the late eighties there were only a couple of different devices available, today we have to choose among some hundreds, with lots of minor and major variations in polymer and structure. As most of the minor variations may not lead to significant change in clinical outcome and may be regarded as less relevant, we should focus on major differences. Eventually, this is used to structure the world of mesh by forming groups of textile devices with distinct biological response. Many experimental and some clinical studies have underlined the outstanding importance of porosity, which fortunately, in contrast to other biomechanical quanlities, is widely unaffected by the anisotropy of meshes.MethodsIn accordance with the major manufacturers of meshes, a classification of meshes was derived from a huge pool of textile data based briefly on the following: (1) large pores, (2) small pores, (3) additional features, (4) no pores, (5) 3D structure and (6) biological origin. At 1,000 explanted meshes the value of this classification was evaluated by group-specific assessment of inflammatory and connective tissue reaction.ResultsApplication of this classification to common products has proved feasable, and each of the six different classes includes devices that in clinical trials failed to show relevant differences in patients' outcome when comparing products within the same group. Furthermore, histological analysis confirmed significant differences in tissue reactions between but not within the different classes.ConclusionsClassifying implants according to a similar response enables grouping patients into comparable cohorts despite implantation of different devices. Furthermore, it enables the examination of the impact of mesh classes for the various indications even from heterogenous data of registries. Finally and not the least, any grouping supports the surgeon to select the best device to meet the individual need and to tailor patients therapy.

Project description:BACKGROUND:All surgical meshes entering the U.S. market have been cleared for clinical use by the 510(k) process of the Food and Drug Administration (FDA), in which devices simply require proof of "substantial equivalence" to predicate devices, without the need for clinical trials. However, recalled meshes associated with adverse effects may, indirectly, continue to serve as predicates for new devices raising concerns over the safety of the 510(k) route. METHODOLOGY:Here we assess the potential magnitude of this problem by determining the ancestral network of equivalence claims linking recently cleared surgical meshes. Using the FDA website we identified all surgical meshes cleared by the 510(k) route between January 2013 and December 2015 along with all listed predicates for these devices. Using a network approach, we trace the ancestry of predicates across multiple generations of equivalence claims and identify those meshes connected to devices that have since recalled from the market along with the reason for their recall. CONCLUSIONS:We find that the 77 surgical meshes cleared between 2013 and 2015 are based on 771 interconnected predicate claims of equivalence from 400 other devices. The vast majority of these devices (97%) are descended from only six surgical meshes that were present on the market prior to 1976. One of these ancestral meshes alone, provided the basis of 183 subsequent devices. Furthermore, we show that 16% of recently cleared devices are connected through equivalence claims to the 3 predicate meshes that have been recalled for design and material related flaws causing serious adverse events. Taken together, our results show that surgical meshes are connected through a tangled web of equivalency claims and many meshes recently cleared by the FDA have connections through chains of equivalency to devices which have been recalled from the market due to concerns over clinical safety. These findings raise concerns over the efficacy of the 510(k) route in ensuring patient safety.

Project description:Biomaterial substrates composed of semi-aligned electrospun fibers are attractive supports for the regeneration of connective tissues because the fibers are durable under cyclic tensile loads and can guide cell adhesion, orientation, and gene expression. Previous studies on supported electrospun substrates have shown that both fiber diameter and mechanical deformation can independently influence cell morphology and gene expression. However, no studies have examined the effect of mechanical deformation and fiber diameter on unsupported meshes. Semi-aligned large (1.75??m) and small (0.60??m) diameter fiber meshes were prepared from degradable elastomeric poly(esterurethane urea) (PEUUR) meshes and characterized by tensile testing and scanning electron microscopy (SEM). Next, unsupported meshes were aligned between custom grips (with the stretch axis oriented parallel to axis of fiber alignment), seeded with C3H10T1/2 cells, and subjected to a static load (50?mN, adjusted daily), a cyclic load (4% strain at 0.25?Hz for 30?min, followed by a static tensile loading of 50?mN, daily), or no load. After 3 days of mechanical stimulation, confocal imaging was used to characterize cell shape, while measurements of deoxyribonucleic acid (DNA) content and messenger ribonucleic acid (mRNA) expression were used to characterize cell retention on unsupported meshes and expression of the connective tissue phenotype. Mechanical testing confirmed that these materials deform elastically to at least 10%. Cells adhered to unsupported meshes under all conditions and aligned with the direction of fiber orientation. Application of static and cyclic loads increased cell alignment. Cell density and mRNA expression of connective tissue proteins were not statistically different between experimental groups. However, on large diameter fiber meshes, static loading slightly elevated tenomodulin expression relative to the no load group, and tenascin-C and tenomodulin expression relative to the cyclic load group. These results demonstrate the feasibility of maintaining cell adhesion and alignment on semi-aligned fibrous elastomeric substrates under different mechanical conditions. The study confirms that cell morphology is sensitive to the mechanical environment and suggests that expression of select connective tissue genes may be enhanced on large diameter fiber meshes under static tensile loads.

Dataset Information

Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model.

Publications

Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model.

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