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Prosthetic mesh infection constitutes one of the major postsurgical complications following abdominal hernia repair. Antibacterial coatings represent a prophylactic strategy to reduce the risk of infection. This study assessed the in vitro response of two antibacterial gels made of 1% carboxymethylcellulose (CMC) functionalized with an antiseptic (chlorhexidine, CHX) or an antibiotic (rifampicin, RIF), developed for the coating of polypropylene (PP) meshes for hernia repair. Fragments of a lightweight PP mesh (1 cm 2 ) presoaked in the unloaded or drug-loaded CMC (0.05% CHX; 0.13 mg/mL RIF) were challenged with 10 6 CFU/mL Staphylococcus aureus (Sa) and methicillin-resistant S. aureus (MRSA). Agar diffusion tests, sonication, turbidimetry, crystal violet staining, scanning electron microscopy and cell viability assays (fibroblasts, mesothelial cells) were performed to evaluate the response of the gels. Both compounds-especially the RIF-loaded gel-exerted a biocidal effect against gram-positive bacteria, developing wide inhibition halos, precluding adhesion to the mesh surface, and hampering bacterial survival in culture. The antibiotic gel proved innocuous, while lower viability was found in cells exposed to the antiseptic ( p < 0.05). Together with their fast, affordable, convenient processing and easy application, the results suggest the potential effectiveness of these drug-loaded CMC gels in providing meshes with an antibacterial coating exhibiting great biocide performance.

To examine the effects of a time-matched endurance vs. concurrent training on circulating IL-6, IL-13, IL-15, IL-15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre- and postmenopause. Thirty-five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1, N  = 10), concurrent training (CON, N  = 13) or no training group (CT, N  = 12). Additionally, twelve sedentary premenopausal women with obesity were added to an endurance training group (EN2, N  = 12). Participants took part in a 12-week supervised intervention, performing 3 sessions/week of 60 min/session. Before and after the interventions, body composition and fitness were assessed, and blood samples obtained to measure serum myokines levels. Total fat mass decreased in all exercised groups (CON,-5.2%; EN1,-5.3%; EN2,-5.6%). In postmenopausal women, serum IL-6, IL-15 and IL-15Ra decreased after training ( P <0.01), finding a pronounced reduction in IL-6 (-42% vs. -16%) and IL-15 (-50% vs. -31%) when comparing EN1 to CON ( P <0.05). Serum FGF21 was only reduced in the EN1 (-27%; P =0.012). While EN1 and EN2 comparison, reported differences for IL-15Rα concentration (-28% vs. -40%; P =0.023). Finally, in EN2, the delta change of fat mass and IL-6, IL-15 and IL-15Rα were associated ( r  = 0.605; r  = 0.546; r  = 0.515; P <0.05). IL-13 showed undetected concentrations. Circulating IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity. Endurance training promotes a higher reduction of these myokines, potentially activating their intricate immune and fat mass regulation roles in postmenopausal women with obesity.

Wound healing includes dynamic processes grouped into three overlapping phases: inflammatory, proliferative, and maturation/remodeling. Collagen is a critical component of a healing wound and, due to its properties, is of great interest in regenerative medicine. This preclinical study was designed to compare the effects of a new collagen-based hydrolysate powder on wound repair to a commercial non-hydrolysate product, in a murine model of cutaneous healing. Circular excisional defects were created on the dorsal skin of Wistar rats ( n = 36). Three study groups were established according to the treatment administered. Animals were euthanized after 7 and 18 days. Morphometric and morphological studies were performed to evaluate the healing process. The new collagen treatment led to the smallest open wound area throughout most of the study. After seven days, wound morphometry, contraction, and epithelialization were similar in all groups. Treated animals showed reduced granulation tissue formation and fewer inflammatory cells, and induction of vasculature with respect to untreated animals. After 18 days, animals treated with the new collagen treatment showed accelerated wound closure, significantly increased epithelialization, and more organized repair tissue. Our findings suggest that the new collagen treatment, compared to the untreated control group, produces significantly faster wound closure and, at the same time, promotes a slight progression of the reparative process compared with the rest of the groups.

Purpose: Atraumatic mesh fixation for abdominal hernia repair has been developed to avoid the disadvantages of classical fixation with sutures, which is considered a cause of chronic pain and discomfort. This study was designed to analyze, in the short and medium term, the biological and mechanical behavior of two self-fixing meshes compared to that of a polypropylene (PP) mesh fixed with a cyanoacrylate (CA) tissue adhesive., Methods: Partial abdominal wall defects (6 × 4 cm) were created in New Zealand rabbits (n = 36) and repaired using a self-adhesive hydrogel mesh (Adhesix™), a self-gripping mesh (ProGrip™) or a PP mesh fixed with CA (Surgipro™ CA). After 14 and 90 days, the host tissue incorporation, macrophage response and biomechanical strength were examined., Results: At 14 and 90 days, the ProGrip and Surgipro CA meshes showed good host tissue incorporation; however, the Adhesix implants presented poor integration, seroma formation and a higher degree of shrinkage. The Adhesix hydrogel was completely reabsorbed at 14 days, whereas ProGrip microhooks were observed at all study times. The macrophage response was higher in the ProGrip and Surgipro CA groups at 14 and 90 days, respectively, and decreased over time. At 90 days, the ProGrip implants showed the highest tensile strength values and the Adhesix implants showed the highest failure stretch., Conclusion: Meshes with mechanical microgrip self-fixation (ProGrip) show better biological and mechanical behavior than those with adhesive hydrogel (Adhesix) in a preclinical model of abdominal hernia repair in rabbits., (© 2022. The Author(s).)

Background: When using a prosthetic material in hernia repair, the behaviour of the mesh at the peritoneal interface is especially important for implant success. Biomaterials developed for their intraperitoneal placement are known as composites and are made up of two different-structure materials, one is responsible for good integration within host tissue and the other is responsible to make contact with the viscera. This study examines the behaviour at the peritoneal level of two composites, the fully degradable Phasix-ST® and the partially degradable Symbotex®. A polypropylene mesh (Optilene®) served as control., Methods: Sequential laparoscopy from 3 to 90 days, in a preclinical model in the New Zealand white rabbit, allowed monitoring adhesion formation. Morphological studies were performed to analyse the neoperitoneum formed in the repair process. Total macrophages were identified by immunohistochemical labelling. To identify the different macrophage phenotypes, complementary DNAs were amplified by qRT-PCR using specific primers for M1 (TNF-α/CXCL9) and M2 (MRC1/IL-10) macrophages., Results: The percentage of firm and integrated adhesions remained very high in the control group over time. Both composites showed a significant decrease in adhesions at all study times and in qualitative terms were mainly loose. Significant differences were also observed from 7 days onwards between the two composites, increasing the values in Phasix over time. Neoperitoneum thickness for Phasix was significantly greater than those of the other meshes, showing mature and organized neoformed connective tissue. Immunohistochemically, a significantly higher percentage of macrophages was observed in Symbotex. mRNA expression levels for the M2 repair-type macrophages were highest for Phasix but significant differences only emerged for IL-10., Conclusions: Fewer adhesions formed to the Symbotex than Phasix implants. Ninety days after implant, total macrophage counts were significantly higher for Symbotex, yet Phasix showed the greater expression of M2 markers related to the tissue repair process., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva with frequent involvement of the corneal limbus. Its pathogenesis has been mainly attributed to sun exposure to ultraviolet-B radiation. Obtained evidence has shown that it is a complex and multifactorial process which involves multiple mechanisms such as oxidative stress, dysregulation of cell cycle checkpoints, induction of inflammatory mediators and growth factors, angiogenic stimulation, extracellular matrix (ECM) disorders, and, most likely, viruses and hereditary changes. In this review, we aim to collect all authors' experiences and our own, with respect to the study of fibroelastic ECM of pterygium. Collagen and elastin are intrinsic indicators of physiological and pathological states. Here, we focus on an in-depth analysis of collagen (types I and III), as well as the main constituents of elastic fibers (tropoelastin (TE), fibrillins (FBNs), and fibulins (FBLNs)) and the enzymes (lysyl oxidases (LOXs)) that carry out their assembly or crosslinking. All the studies established that changes in the fibroelastic ECM occur in pterygium, based on the following facts: An increase in the synthesis and deposition of an immature form of collagen type III, which showed the process of tissue remodeling. An increase in protein levels in most of the constituents necessary for the development of elastic fibers, except FBLN4, whose biological roles are critical in the binding of the enzyme LOX, as well as FBN1 for the development of stable elastin. There was gene overexpression of TE, FBN1, FBLN5, and LOXL1, while the expression of LOX and FBLN2 and -4 remained stable. In conclusion, collagen and elastin, as well as several constituents involved in elastic fiber assembly are overexpressed in human pterygium, thus, supporting the hypothesis that there is dysregulation in the synthesis and crosslinking of the fibroelastic component, constituting an important pathogenetic mechanism for the development of the disease.

Abdominal hernia repair using prosthetic materials is among the surgical interventions most widely performed worldwide. These materials, or meshes, are implanted to close the hernial defect, reinforcing the abdominal muscles and reestablishing mechanical functionality of the wall. Meshes for hernia repair are made of synthetic or biological materials exhibiting multiple shapes and configurations. Despite the myriad of devices currently marketed, the search for the ideal mesh continues as, thus far, no device offers optimal tissue repair and restored mechanical performance while minimizing postoperative complications. Additive manufacturing, or 3D-printing, has great potential for biomedical applications. Over the years, different biomaterials with advanced features have been successfully manufactured via 3D-printing for the repair of hard and soft tissues. This technological improvement is of high clinical relevance and paves the way to produce next-generation devices tailored to suit each individual patient. This review focuses on the state of the art and applications of 3D-printing technology for the manufacture of synthetic meshes. We highlight the latest approaches aimed at developing improved bioactive materials (e.g., optimizing antibacterial performance, drug release, or device opacity for contrast imaging). Challenges, limitations, and future perspectives are discussed, offering a comprehensive scenario for the applicability of 3D-printing in hernia repair.

Background: Antibacterial meshes for hernia repair seek to avoid infection in the patient. As these biomaterials are especially prone to bacteria settling at their sutured borders, this study examines whether the use of a cyanoacrylate tissue adhesive could improve mesh behavior at the fixation zones., Methods: First, antibacterial polypropylene meshes were prepared by soaking in 0.05% chlorhexidine, and the response of n-hexyl cyanoacrylate to contamination with Staphylococcus aureus ATCC25923 was assessed in vitro. Then, in a preclinical model, partial defects (5 x 3 cm) were created in the abdominal wall of 18 New Zealand White rabbits and repaired with mesh to establish the following 3 study groups: (1) mesh without chlorhexidine fixed with cyanoacrylate, (2) antibacterial mesh fixed with sutures, and (3) antibacterial mesh fixed with cyanoacrylate (n = 6 each). The implants were inoculated with 10 6 CFU/mL of S aureus. At 14 days after surgery, bacterial adhesion to the implant and its integration within host tissue were determined through microbiological, histological and immunohistochemical procedures., Results: As observed in vitro, the cyanoacrylate gave rise to a 1.5-cm bacteria-free margin around the prosthetic mesh. In vivo, the tissue adhesive prevented bacterial adhesion to the fixation zones, reducing infection of chlorhexidine-free meshes and optimizing the efficacy of the antibacterial meshes compared with those fixed with sutures., Conclusion: These findings indicated that cyanoacrylate fixation does not affect mesh integration into the host tissue. Likewise, the antibacterial behavior and tissue response of a chlorhexidine-treated polypropylene mesh is improved when cyanoacrylate is used for its fixation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Prosthetic mesh infection is a devastating complication of abdominal hernia repair which impairs natural healing in the implant area, leading to increased rates of patient morbidity, mortality, and prolonged hospitalization. This preclinical study was designed to assess the effects on abdominal wall tissue repair of coating meshes with a chlorhexidine or rifampicin-carboxymethylcellulose biopolymer gel in a Staphylococcus aureus ( S. aureus ) infection model. Partial abdominal wall defects were created in New Zealand white rabbits ( n = 20). Four study groups were established according to whether the meshes were coated or not with each of the antibacterial gels. Three groups were inoculated with S. aureus and finally repaired with lightweight polypropylene mesh. Fourteen days after surgery, implanted meshes were recovered for analysis of the gene and protein expression of collagens, macrophage phenotypes, and mRNA expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Compared to uncoated meshes, those coated with either biopolymer gel showed higher collagen 1/3 messenger RNA and collagen I protein expression, relatively increased VEGF mRNA expression, a significantly reduced macrophage response, and lower relative amounts of MMPs mRNAs. Our findings suggest that following mesh implant these coatings may help improving abdominal wall tissue repair in the presence of infection.

Biomaterials and their applications are perhaps among the most dynamic areas of research within the field of biomedicine. Any advance in this topic translates to an improved quality of life for recipient patients. One application of a biomaterial is the repair of an abdominal wall defect whether congenital or acquired. In the great majority of cases requiring surgery, the defect takes the form of a hernia. Over the past few years, biomaterials designed with this purpose in mind have been gradually evolving in parallel with new developments in the different surgical techniques. In consequence, the classic polymer prosthetic materials have been the starting point for structural modifications or new prototypes that have always strived to accommodate patients' needs. This evolving process has pursued both improvements in the wound repair process depending on the implant interface in the host and in the material's mechanical properties at the repair site. This last factor is important considering that this site-the abdominal wall-is a dynamic structure subjected to considerable mechanical demands. This review aims to provide a narrative overview of the different biomaterials that have been gradually introduced over the years, along with their modifications as new surgical techniques have unfolded.

The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide- co -glycolide) (PLGA) nanoparticles loaded with chlorhexidine or rifampicin. The chlorhexidine-loaded system exhibited a burst release during the first day reaching the release of the loaded drug in three or four days, whereas rifampicin was gradually released for at least 11 days. Both antibacterial coated meshes were highly active against Staphylococcus aureus and Staphylococcus epidermidis (10 6 CFU/mL), displaying zones of inhibition that lasted for 7 days (chlorhexidine) or 14 days (rifampicin). Apparently, both systems inhibited bacterial growth in the surrounding environment, as well as avoided bacterial adhesion to the mesh surface. These polymeric coatings loaded with biodegradable nanoparticles containing antimicrobials effectively precluded bacterial colonization of the biomaterial. Both biocomposites showed adequate performance and thus could have potential application in the design of antimicrobial coatings for the prophylactic coating of polypropylene materials for hernia repair.

The prophylactic coating of prosthetic mesh materials for hernia repair with antimicrobial compounds is commonly performed before implantation of the mesh in the abdominal wall. We propose a novel alternative, which is a rifampicin-loaded thermo-responsive hydrogel formulation, to be applied on the mesh after its implantation. This formulation becomes a gel in-situ once reached body temperature, allowing an optimal coating of the mesh along with the surrounding tissues. In vitro, the hydrogel cytotoxicity was assessed using rabbit fibroblasts and antimicrobial efficacy was determined against Staphylococcus aureus . An in vivo rabbit model of hernia repair was performed; implanted polypropylene meshes (5 × 2 cm) were challenged with S. aureus (10 6 CFU), for two study groups-unloaded (n = 4) and 0.1 mg/cm 2 rifampicin-loaded hydrogel (n = 8). In vitro, antibacterial activity of the hydrogel lasted for 5 days, without sign of cytotoxicity. Fourteen days after implantation, meshes coated with drug-free hydrogel developed a strong infection and resulted in poor tissue integration. Coating meshes with the rifampicin-loaded hydrogel fully prevented implant infection and permitted an optimal tissue integration. Due to its great performance, this, degradable, thermo-responsive antimicrobial hydrogel could potentially be a strong prophylactic armamentarium to be combined with prosthesis in the surgical field.

Background: In hernia surgery, soaking of meshes in antibiotics before implantation is a prophylactic strategy for minimizing the risk of infection while providing minimal, local, drug doses. This study describes the development and application of an antibacterial mesh coating comprising a carboxymethylcellulose gel loaded with rifampicin in a preclinical model of Staphylococcus aureus and S. epidermidis infection in rabbits., Methods: Antibacterial activity and cytocompatibility (with fibroblasts) of unloaded carboxymethylcellulose gel and 0.13 mg/mL rifampicin-carboxymethylcellulose gel were assessed in vitro. Then, partial abdominal wall defects (5 × 2 cm) were created in New Zealand white rabbits (n = 34), the wound inoculated with 0.25 mL of 10 6 CFU Staphylococcus aureus/ S. epidermidis (n = 17 each), and the defect then repaired with a lightweight, monofilament, large pore polypropylene mesh either uncoated (n = 3) or coated with carboxymethylcellulose gel (n = 7) or rifampicin-carboxymethylcellulose gel (n = 7). By postoperative day 14, coating performance was evaluated by determining bacterial adhesion (via sonication), host tissue incorporation (via histology), macrophage response via immunostaining), and bloodstream drug diffusion (via high-performance liquid chromatography)., Results: In vitro, rifampicin-carboxymethylcellulose gel demonstrated great activity against Staphylococcus aureus/S. epidermidis, while being innocuous for fibroblasts. In vivo, rifampicin-carboxymethylcellulose gel-coated implants displayed full bacterial clearance and optimal tissue integration, irrespective of the strain of Staphylococcus. In contrast, uncoated and carboxymethylcellulose gel-coated implants exhibited macro/microscopic signs of infection and impaired tissue integration. Macrophage responses were less in rifampicin-carboxymethylcellulose gel implants than in uncoated mesh (Staphylococcus aureus/S. epidermidis; P < .01) and carboxymethylcellulose gel (S. epidermidis; P < .05) implants. Bloodstream levels of rifampicin were undetectable., Conclusion: Soaking meshes in rifampicin-carboxymethylcellulose gel inhibited effectively the bacterial adhesion to the mesh without compromising the tissue repair. This antibiotic gel constitutes an easy-to-use and effective prophylactic strategy that potentially reduce the prevalence of postoperative mesh infection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Tissue adhesives are a feasible option to fix a hernia repair mesh, avoiding tissue trauma of suture fixation. Classically, they are applied in the form of a drop, although novel applications such as spray are emerging. This study compares the use of a new experimental cyanoacrylate (n-butyl) in the form of a spray or drops., Materials and Methods: Three study groups of New Zealand White rabbits were established (n = 6 each) according to the method used to fix a 5 × 3 cm polypropylene mesh in a partial abdominal wall defect model: control group (polypropylene stitches), adhesive drops group, and adhesive spray group. Morphological, immunohistochemical, and biomechanical strength studies were performed at 14 d postimplant. Collagen 1/3 gene ratio was determined by quantitative reverse transcription polymerase chain reaction., Results: In the drops group, the adhesive obstructed the mesh pores and prevented tissue infiltration at the points of application. When the adhesive was applied as a spray, although more numerous, adhesive deposits were smaller and allowed for better host tissue infiltration into the mesh. The inflammatory response was similar in the adhesive groups and more intense than in the control group. Collagen 1/3 mRNA ratio was significantly higher in the spray than the control group. The mechanical resistance of the meshes was similar in all three groups., Conclusions: The application of the cyanoacrylate adhesive in the form of spray to fix polypropylene meshes in an animal model had a similar inflammatory response compared with droplet application. Neither application impacted the mechanical strength of the repaired area. An increased in collagen 1/3 ratio was found with cyanoacrylate spray compared with suture, and future studies should focus on this pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Reticular hybrid meshes represent an alternative material for intraperitoneal repair of abdominal hernias. These consist of a reticular mesh coated or interwoven/knitted with inert materials. This study assesses the performance of two reticular polypropylene-containing hybrid meshes, TiMESH (coated with titanium) and DynaMesh (interwoven with polyvinylidene fluoride), in vitro, as well as their efficiency in adhesion prevention and tissue incorporation in an intraperitoneal model., Methods: The mesothelialization capacity of TiMESH and DynaMesh was evaluated in vitro and compared to that of Surgipro (reticular bare polypropylene) and Preclude (laminar expanded polytetrafluoroethylene). Mesh fragments were placed on the intact parietal peritoneum of New Zealand white rabbits (n = 24), and laparoscopy performed 7 days post-surgery. Fourteen days post-implantation, adhesions were evaluated and host tissue incorporation, macrophage response, collagen expression (immunohistochemistry/RT-PCR) and neoperitoneum formation assessed. Adhesions and omental tissue were also examined., Results: Mesh pores in reticular meshes were devoid of cells in the in vitro study. TiMESH, DynaMesh and Surgipro showed similar adhesion rates at 7/14 days and optimal tissue integration, with significant differences in comparison to Preclude. The greatest presence of macrophages was observed for TiMESH and was significant versus that for Preclude. Hybrid meshes revealed significantly higher collagen 1 mRNA expression in implants, with no differences in the levels of collagen 3. Omental samples from animals with a reticular mesh showed significantly greater collagen 1 mRNA levels., Conclusions: The reticular structure of a mesh limits the formation of a continuous mesothelial monolayer in vitro, regardless of its composition. The presence of titanium as a coating or polyvinylidene fluoride interwoven with polypropylene in a reticular structure did not prevent adhesions. The hybrid meshes showed proper integration and an increase in the mRNA Col 1 levels in the implant area compared to Surgipro or Preclude., Competing Interests: The authors have declared that no competing interests exist.

In this study, rat models of wound closure by first and second intention were developed to evaluate the influence that two immunosuppressants for treating multiple sclerosis (fingolimod, azathioprine) have on wound healing. Sixty-three Sprague-Dawley rats were daily treated with fingolimod (0.6 mg/kg), azathioprine (2.5 mg/kg), or placebo (saline). Following 6 weeks of treatment, a linear incision (1.5 cm) or a circular excisional defect (diameter 1.5 cm) was made on the dorsal skin. The treatments were uninterrupted and after 7 days (incisional) or 21 days (incisional, excisional), animals were euthanized (n = 7 per group and time-point). Morphometric (wound closure), histological (stainings), and immunofluorescent studies (macrophages) were performed to evaluate the healing process. For both the incisional and excisional defects, animals treated with fingolimod exhibited a healing process equivalent to that of placebo in terms of collagenization, wound closure, and macrophage response. By comparison, groups treated with azathioprine displayed a delay in healing times which was especially evident in the excisional defect, where inflammatory reaction and collagen deposition in the repair tissue remained active by day 21. These results show that immunosuppressants with a selective mechanism of action (fingolimod) can have less impact on wound healing than their classical nonselective counterparts (azathioprine)., (© 2018 by the Wound Healing Society.)

Introduction: Lightweight (LW) polypropylene (PP) meshes better adapt to host tissue, causing less fibrosis and inflammatory responses than high-density meshes. Mesh fixation using tissue adhesives (TA) that replace conventional sutures may improve the process of hernia repair and tissue trauma. This preclinical study compares the behavior of different cyanoacrylate-based adhesives in the fixation of LW-PP meshes for hernia repair., Methods: Partial abdominal wall defects were repaired using LW-PP Optilene meshes in New Zealand rabbits. The following groups were established according to the mesh fixation method: Suture (control), Glubran 2 (n-butyl), Ifabond (n-hexyl), SafetySeal (n-butyl) and Evobond (n-octyl). At 14, 90 and 180 days after surgery, the recovered implants were examined to assess the host tissue integration, the macrophage response and the biomechanical strength., Results: All the groups showed optimal host tissue incorporation regardless of the fixation procedure. Significantly increased levels of collagen 1 and collagen 3 gene expression (p<0.001) were observed at 14 days compared to the medium- and long-term durations, where the Suture and Glubran groups showed the highest expression of collagen 1. All the adhesives increased the macrophage reaction (p<0.001) compared to sutures at all implant times. Maximal macrophage response was observed in the short-term Glubran group (p<0.01) compared to the rest of the groups. Although SafetySeal and Evobond did not reach the biomechanical resistance of sutures at 14 days, all the adhesives did reach this level in the medium- to long-term periods, providing significantly higher resistance (p<0.05)., Conclusions: All the cyanoacrylates, despite inducing a significantly increased macrophage response versus sutures, showed optimal host tissue integration and long-term mechanical behavior; thus, they might be good choices for LW-PP mesh hernia repairs., Competing Interests: The authors have declared that no competing interests exist.

Background: As an alternative to sutures, meshes used for hernia repair can be fixed using cyanoacrylate-based adhesives. Attempts to improve these adhesives include alkyl-chain lengthening to reduce their toxicity. This preclinical study compares the long-term behavior of cyanoacrylates of different chain lengths already used in hernia repair and new ones for this application., Materials and Methods: Partial abdominal wall defects were repaired using a Surgipro mesh in 18 New Zealand White rabbits, and groups were established according to the mesh fixation method: sutures (control), Glubran 2 (n-butyl), Ifabond (n-hexyl), and the new adhesives SafetySeal (n-butyl), and Evobond (n-octyl). Six months after surgery, recovered implants were examined to assess adhesive degradation, host tissue reaction, and biomechanical strength., Results: All the cyanoacrylate groups showed good host tissue incorporation in the meshes. Macrophage responses to Glubran and Ifabond were quantitatively greater compared with sutures. Cell damage caused by the adhesives was similar, and only Glubran induced significantly more damage than sutures. Significantly lower collagen 1/3 messenger RNA expression was induced by Ifabond than the remaining fixation materials. No differences were observed in collagen expression except slightly reduced collagen I deposition in Glubran/Ifabond and collagen III deposition in the suture group. Mechanical strengths failed to vary between the suture and cyanoacrylate groups., Conclusions: All cyanoacrylates showed good long-term behavior and tolerance irrespective of their long or intermediate chain length. Cyanoacrylate residues persisted at 6 mo, indicating their incomplete degradation. Biomechanical strengths were similar both for the adhesives and sutures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this report, we review the use of the New Zealand White rabbit as the experimental animal for several models of abdominal wall repair. For the repair of an abdominal wall defect, such as a hernia in clinical practice, multiple types of prosthetic material exist. Before their marketing, each of these biomaterials needs to be tested in a preclinical setting to confirm its biocompatibility and appropriate behavior at the different tissue interfaces. For preclinical trials, we have always used the New Zealand White rabbit as the model owing to its ease of handling and suitable size. This size allows for laparoscopic studies designed to follow the behavior in real time of a biomaterial implanted at the peritoneal interface, a delicate interface that often gives rise to complications in human practice. The size of the rabbit also offers a sufficiently large number of implant samples to be harvested for a complete battery of tests at several time points postimplant. In this review, we first describe the models established and then provide the results obtained so far using these models to test the different types of biomaterial. We end our review with a discussion of the clinical implications of these results.

The less traumatic use of surgical adhesives rather than sutures for mesh fixation in hernia repair has started to gain popularity because they induce less host tissue damage and provoke less postoperative pain. This study examines the host tissue response to a new cyanoacrylate (CA) adhesive (n-octyl, OCA). Partial defects (3 × 5 cm) created in the rabbit anterior abdominal wall were repaired by mesh fixation using OCA, Glubran2 ® (n-butyl-CA), Ifabond ® (n-hexyl-CA) or sutures. Samples were obtained at 14/90 days for morphology, collagens qRT-PCR/immunofluorescence and biomechanical studies. All meshes were successfully fixed. Seroma was detected mainly in the Glubran group at 14 days. Meshes fixed using all methods showed good host tissue incorporation. No signs of degradation of any of the adhesives were observed. At 14 days, collagen 1 and 3 mRNA expression levels were greater in the suture and OCA groups, and lower in Ifabond, with levels varying significantly in the latter group with respect to the others. By 90 days, expression levels had fallen in all groups, except for collagen 3 mRNA in Ifabond. Collagen I and III protein expression was marked in the suture and OCA groups at 90 days, but lower in Ifabond at both time points. Tensile strengths were similar across groups. Our findings indicate the similar behavior of the adhesives to sutures in terms of good tissue incorporation of the meshes and optimal repair zone strength. The lower seroma rate and similar collagenization to controls induced by OCA suggests its improved behavior over the other two glues. This article deals with a preclinical study to examine different aspects of the repair process in the host of three alkyl cyanoacrylates (n-butyl (GLUBRAN 2), n-hexyl (IFABOND), and n-octyl cyanoacrylate (EVOBOND)) compared to sutures (control), in the fixation of surgical meshes for hernia repair. It goes into detail about collagen deposition in the repair zone at short and medium term. The results obtained demonstrate lower seroma rate and similar collagenization to sutures induced by the n-octyl suggesting better behavior than the other two cyanoacrylates.

Aims: This study examines the intraperitoneal behavior of two cyanoacrylate tissue adhesives: Ifabond ® and a new, non-marketed octyl cyanoacrylate adhesive (OCA) used for the intraperitoneal fixation of a laminar expanded polytetrafluoroethylene (ePTFE) mesh., Material and Methods: In 36 New Zealand White rabbits, 3 × 3 cm (n = 24) or 1.5 × 3 cm (n = 12) fragments of ePTFE mesh (Preclude ® , Gore, Flagstaff, USA) were fixed to the parietal peritoneum using OCA or Ifabond ® . Peritoneal fluid was obtained at the time of implant and at 2 weeks postimplant for determination of the cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). At 14 or 90 days postsurgery, the animals were euthanized and the meshes excised to assess host tissue incorporation, the macrophage response, apoptosis and fixation strength (T-peel tensiometry)., Results: Peritoneal fluid IL-6 and TNF-α concentrations were similar in the OCA and Ifabond ® groups. Both adhesives gave rise to adequate mesothelialization of the laminar ePTFE. Macrophage counts were similar for the two study groups, but a significantly increase in macrophage response was observed from 14 to 90 days for Ifabond ® . At 90 days postimplant, apoptotic cell counts was lower for the implants fixed with OCA and a fixation strength was significantly lower for OCA., Conclusions: Despite similar cytokine levels at 2 weeks and similar host tissue incorporation observed for the meshes fixed with the two adhesives, the use of Ifabond ® gave rise to a greater apoptosis rate, although this adhesive provided a stronger fixation bond. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 312-319, 2017., (© 2015 Wiley Periodicals, Inc.)

Background: Synthetic tissue adhesives (TA) are sometimes used in hernia repair surgery. This study compares the use of a new, noncommercial, long-chain cyanoacrylate (n-octyl) TA and Ifabond for mesh fixation., Materials and Methods: In two implant models in the rabbit, expanded polytetrafluorethylene meshes were fixed to the parietal peritoneum using a TA or tacks (intraperitoneal model), or polypropylene meshes used to repair partial abdominal wall defects were fixed with a TA or sutures (extraperitoneal model). Animals were euthanized 14 or 90 d postsurgery and implant specimens were processed for microscopy (labeling of macrophages and apoptotic cells), peritoneal fluid and biomechanical strength testing. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determinated in peritoneal fluid., Results: Mesothelial cell deposition on the intraperitoneal implants fixed using the new TA and Ifabond was adequate and similar IL-6 and TNF-α levels were detected in these implants. Intraperitoneal meshes fixed with tacks showed IL-6 overexpression. Three months after surgery, macrophage and apoptotic cell rates were higher for the intraperitoneal implants fixed with Ifabond versus the new TA or tacks. In the extraperitoneal model, reduced macrophage and cell damage responses were observed in the meshes fixed with sutures versus both TA. Tensile strengths were greater for the tacks versus TA in the intraperitoneal implants and similar for the sutures and TA in the extraperitoneal implants (90 d)., Conclusions: Both TA showed a good cell response in both models. Their use in an intraperitoneal location resulted in reduced tensile strength compared with the tacks. However, strengths were comparable when extraperitoneal implants were fixed with these adhesives or sutures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The article deals with a comparative analysis of the parameters of the polymerization in physiological conditions of three commercially available alkyl cyanoacrylates, n-butyl cyanoacrylate (GLUBRAN 2), n-hexyl cyanoacrylate (IFABOND), and n-octyl cyanoacrylate (EVOBOND), the cell behavior of the corresponding polymers and the application of these adhesives in the fixation of surgical polypropylene meshes for hernia repair in an animal model of rabbits. The results obtained demonstrate that the curing process depends on the nature of the alkyl residue of the ester group of cyanoacrylate molecules, being the heat of polymerization lower for the octyl derivative in comparison with the hexyl and butyl, and reaching a maximum temperature of 35 °C after a time of mixing with physiological fluids of 60-70 s. The cell behavior demonstrates that the three systems do not present toxicity for fibroblasts and low adhesion of cells, which is a positive result for application as tissue adhesives, especially for the fixation of abdominal polypropylene meshes for hernia repair. The animal experimentation indicates the excellent tolerance of the meshes fixed with the cyanoacrylic adhesives, during at least a period of 90 d, and guarantees a good adhesion for the application of hernia repair meshes., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cyanoacrylate(CA)-based tissue adhesives, although not widely used, are a feasible option to fix a mesh during abdominal hernia repair, due to its fast action and great bond strength. Their main disadvantage, toxicity, can be mitigated by increasing the length of their alkyl chain. The objective was to assess the in vitro cytotoxicity and in vivo biocompatibility in hernia repair of CAs currently used in clinical practice (Glubran(n-butyl) and Ifabond(n-hexyl)) and a longer-chain CA (OCA(n-octyl)), that has never been used in the medical field., Methods: Formaldehyde release and cytotoxicity of unpolymerized(UCAs) and polymerized CAs(PCAs) were evaluated by macroscopic visual assessment, flow cytometry and Alamar Blue assays. In the preclinical evaluation, partial defects were created in the rabbit abdominal wall and repaired by fixing polypropylene prostheses using the CAs. At 14 days post-surgery, animals were euthanized for morphology, macrophage response and cell damage analyses., Results: Formaldehyde release was lower as the molecular weight of the monomer increased. The longest side-chain CA(OCA) showed the highest cytotoxicity in the UCA condition. However, after polymerization, was the one that showed better behavior on most occasions. In vivo, all CAs promoted optimal mesh fixation without displacements or detachments. Seroma was evident with the use of Glubran, (four of six animals: 4/6) and Ifabond (2/6), but it was reduced with the use of OCA (1/6). Significantly greater macrophage responses were observed in groups where Glubran and Ifabond were used vs. sutures and OCA. TUNEL-positive cells were significantly higher in the Glubran and OCA groups vs. the suture group., Conclusions: Although mild formaldehyde release occurred, OCA was the most cytotoxic during polymerization but the least once cured. The CAs promoted proper mesh fixation and have potential to replace traditional suturing techniques in hernia repair; the CAs exhibited good tissue integration and effective short-term biocompatibility, with the slightest seroma and macrophage response induced by OCA.

Background: The use of a prosthetic mesh to repair a tissue defect may produce a series of post-operative complications, among which infection is the most feared and one of the most devastating. When occurring, bacterial adherence and biofilm formation on the mesh surface affect the implant's tissue integration and host tissue regeneration, making preventive measures to control prosthetic infection a major goal of prosthetic mesh improvement., Methods: This article reviews the literature on the infection of prosthetic meshes used in hernia repair to describe the in vitro and in vivo models used to examine bacterial adherence and biofilm formation on the surface of different biomaterials. Also discussed are the prophylactic measures used to control implant infection ranging from meshes soaked in antibiotics to mesh coatings that release antimicrobial agents in a controlled manner., Results: Prosthetic architecture has a direct effect on bacterial adherence and biofilm formation. Absorbable synthetic materials are more prone to bacterial colonization than non-absorbable materials. The reported behavior of collagen biomeshes, also called xenografts, in a contaminated environment has been contradictory, and their use in this setting needs further clinical investigation. New prophylactic mesh designs include surface modifications with an anti-adhesive substance or pre-treatment with antibacterial agents or metal coatings., Conclusions: The use of polymer coatings that slowly release non-antibiotic drugs seems to be a good strategy to prevent implant contamination and reduce the onset of resistant bacterial strains. Even though the prophylactic designs described in this review are mainly focused on hernia repair meshes, these strategies can be extrapolated to other implantable devices, regardless of their design, shape or dimension.

Background: Bioprostheses represent a significant advance in the abdominal wall reconstruction since they become degraded until their complete elimination in the recipient organism. This study examines remodeling in the host of three noncrosslinked porcine dermal collagen biomeshes: Strattice™ (St; LifeCell Corp.), XCM Biologic® Tissue Matrix (XCM; Synthes CMF) and Protexa® (Pr; Deco Med S.R.L.)., Methods: Partial ventral hernia defects created in New Zealand White rabbits were repaired using the biomeshes that were placed in an inlay, preperitoneal position. At 14 and 90 days after implantation, explants were assessed in terms of their host tissue incorporation by morphological studies, collagen gene/protein expression (quantitative real-time PCR/immunofluorescence), macrophage response (immunohistochemistry) and biomechanical strength., Results: There were no cases of mortality or infection. Among our macroscopic findings, the mesh detachment detected in one third of the Pr implants at 90 days was of note. The host tissue response to all the biomeshes was similar at both time points, with a tendency observed for their encapsulation. There were no appreciable signs of mesh degradation. The extent of host tissue infiltration and collagenization was greater for St and Pr than for XCM. Macrophages were observed in zones of inflammation and tissue infiltration inside the mesh. XCM showed a greater macrophage response at 90 days (p < 0.05). Improved tensile strength was observed for St (p < 0.05) over Pr and unrepaired defects., Conclusions: St showed the best behavior, featuring good collagenization and tensile strength while also inducing a minimal foreign body reaction., (© 2015 S. Karger AG, Basel.)

Introduction: Prosthetic mesh infection constitutes one of the major complications following hernia repair. Antimicrobial, non-antibiotic biomaterials have the potential to reduce bacterial adhesion to the mesh surface and adjacent tissues while avoiding the development of novel antibiotic resistance. This study assesses the efficacy of presoaking reticular polypropylene meshes in chlorhexidine or a chlorhexidine and allicin combination (a natural antibacterial agent) for preventing bacterial infection in a short-time hernia-repair rabbit model., Methods: Partial hernia defects (5 x 2 cm) were created on the lateral right side of the abdominal wall of New Zealand White rabbits (n = 21). The defects were inoculated with 0.5 mL of a 106 CFU/mL Staphylococcus aureus ATCC25923 strain and repaired with a DualMesh Plus antimicrobial mesh or a Surgipro mesh presoaked in either chlorhexidine (0.05%) or allicin-chlorhexidine (900 μg/mL-0.05%). Fourteen days post-implant, mesh contraction was measured and tissue specimens were harvested to evaluate bacterial adhesion to the implant surface (via sonication, S. aureus immunolabeling), host-tissue incorporation (via staining, scanning electron microscopy) and macrophage response (via RAM-11 immunolabeling)., Results: The polypropylene mesh showed improved tissue integration relative to the DualMesh Plus. Both the DualMesh Plus and the chlorhexidine-soaked polypropylene meshes exhibited high bacterial clearance, with the latter material showing lower bacterial yields. The implants from the allicin-chlorhexidine group displayed a neoformed tissue containing differently sized abscesses and living bacteria, as well as a diminished macrophage response. The allicin-chlorhexidine coated implants exhibited the highest contraction., Conclusions: The presoaking of reticular polypropylene materials with a low concentration of chlorhexidine provides the mesh with antibacterial activity without disrupting tissue integration. Due to the similarities found with the antimicrobial DualMesh Plus material, the chlorhexidine concentration tested could be utilized as a prophylactic treatment to resist infection by prosthetic mesh during hernia repair.

Development of an efficient vascular substitute by tissue engineering is strongly dependent on endothelial cell viability. The aim of this study was to evaluate cell viability of transdifferentiated endothelial-like cells (Tr-ELC) by using for the first time electron probe X-ray microanalysis (EPXMA), not only to accurately analyze cell viability by quantifying the intracellular ionic concentrations, but also to establish their possible use in vascular tissue engineering protocols. Human umbilical cord Wharton's jelly stem cells (HWJSC) and endothelial cells from the human umbilical vein (HUVEC) were isolated and cultured. Transdifferentiation from HWJSC to the endothelial phenotype was induced. EPXMA was carried out to analyze HUVEC, HWJSC and Tr-ELC cells by using a scanning electron microscope equipped with an EDAX DX-4 microanalytical system and a solid-state backscattered electron detector. To determine total ion content, the peak-to-local-background (P/B) ratio method was used with reference to standards composed of dextran containing known amounts of inorganic salts. Our results revealed a high K/Na ratio in Tr-ELC (9.41), in association with the maintenance of the intracellular levels of chlorine, phosphorous and magnesium and an increase of calcium (p=0.031) and sulfur (p=0.022) as compared to HWJSC. Calcium levels were similar for HUVEC and Tr-ELC. These results ensure that transdifferentiated cells are highly viable and resemble the phenotypic and microanalytical profile of endothelial cells. Tr-ELC induced from HWJSC may fulfill the requirements for use in tissue engineering protocols applied to the vascular system at the viability and microanalytical levels.

Introduction: Presoaking meshes for hernia repair with antiseptics prior to implantation could decrease the adhesion of microorganisms to the material surface and reduce the risk of antibiotic resistances. In this work, we evaluate chlorhexidine and allicin (natural antiseptic not yet tested for these purposes) against vancomycin as antiseptics to be used in the pretreatment of a heavyweight polypropylene mesh using an in vitro model of bacterial contamination., Methods: Solutions of saline, vancomycin (40 µg/mL), allicin (1,000 µg/mL), chlorhexidine (2%-0.05%) and the combination allicin-chlorhexidine (900 µg/mL-0.05%) were analyzed with agar diffusion tests in the presence of 106 CFU Staphylococcus aureus ATCC25923. Additionally, sterile fragments of Surgipro (1 cm2) were soaked with the solutions and cultured onto contaminated agar plates for 24/48/72 h. The antimicrobial material DualMesh Plus was utilized as positive control. At every time, the inhibition zones were measured and the bacterial adhesion to the mesh surface quantified (sonication, scanning electron microscopy). Cytotoxicity of the treatments was examined (alamarBlue) using rabbit skin fibroblasts., Results: The largest zones of inhibition were created by allicin-chlorhexidine. Chlorhexidine was more effective than vancomycin, and allicin lost its effectiveness after 24 h. No bacteria adhered to the surface of the DualMesh Plus or the meshes soaked with vancomycin, chlorhexidine and allicin-chlorhexidine. On the contrary, saline and allicin allowed adherence of high loads of bacteria. Vancomycin had no toxic effects on fibroblasts, while allicin and chlorhexidine exerted high toxicity. Cytotoxicity was significantly reduced with the allicin-chlorhexidine combination., Conclusions: The use of antiseptics such as chlorhexidine, alone or combined with others like allicin, could represent an adequate prophylactic strategy to be used for hernia repair materials because soaking with these agents provides the mesh with similar antibacterial properties to those observed after soaking with vancomycin, similar to the effect of DualMesh Plus.

Background: The use of a prosthetic material is the best treatment option for ventral hernia repair; one of the most frequently performed abdominal surgery procedures. This preclinical study compares the behavior of a new mesh (Parietex composite ventral patch [Ptx]) with that of two existing meshes used for ventral hernia repair., Materials and Methods: Fifty-four New Zealand White rabbits (3000 g) were used in an experimental model of umbilical hernia repair (diameter 1.5 cm). The materials tested were: Ventralex ST hernia patch (Vent) (Bard Davol Inc, Warwick, RI) (n = 18); Proceed ventral patch (Ethicon, Somerville, NJ) (PVP) (n = 18) and Ptx (Covidien, Sofradim, Trevoux, France) (n = 18). At 3, 7, 14 d, and 6 wk after implant, peritoneal behavior and adhesion formation were assessed by sequential laparoscopy. Mesh mesothelial cover was determined by scanning electron microscopy. Host tissue ingrowth (collagens I and III) and the macrophage response were assessed by immunohistochemical labeling. Animals were euthanized at 2, 6 wk, and 6 mo after surgery. Data were compared using the Mann-Whitney U test., Results: Adhesion formation from 3 d-6 wk was significantly greater (P < 0.05) for PVP compared with Vent or Ptx. Three encapsulated PVP implants showed "tissue-integrated" adhesions affecting the intestinal loops. All three implant types showed similar patterns of collagen l and III deposition. The PVP mesh elicited the greater macrophage response both at 2 wk and 6 mo., Conclusions: Ptx and Vent showed excellent mesothelialization, which led to minimum adhesion formation. The appropriate tissue integration of Ptx in the parietal neoperitoneum is likely attributable to its deployment system., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Midline laparotomy closure carries a significant risk of incisional hernia. This study examines the behavior of two new suture materials, an elastic material, polyurethane (PUe), and a barbed polydioxanone (PDXb) suture thread in a rabbit model of midline incision closure., Methods: Three 2-cm midline incisions were made in 68 New Zealand White rabbits. The incisions were closed by running suture using four 3/0 threads: polypropylene (PP) (Surgipro®, Covidien), PUe (Assuplus®, Assut Europe), PDX (Assufil®, Assut Europe) or PDXb (Filbloc®, Assut Europe). Animals in each suture group were euthanized 3 weeks and 6 months after surgery. Histological sections of the tissue-embedded sutures were subjected to morphological, collagen expression, macrophage response and uniaxial tensiometry studies., Results: No signs of wound dehiscence or complications were observed. At 3 weeks, all sutures were surrounded by connective tissue composed mainly of collagen III. PUe showed greater collagen I expression than the other sutures. All sutures elicited a macrophage response that diminished from 3 weeks to 6 months (p < 0.001). This response was similar for the non-reabsorbable sutures (PP and PUe) yet PDXb showed a significantly greater response than the other reabsorbable suture (PDX) at 3 weeks (p < 0.01). At this early time point, the tensile strength of PUe was similar to that of control intact tissue (p > 0.05)., Conclusion: Three weeks after surgery, PUe revealed more collagen I deposition than the remaining materials and this translated to a similar biomechanical behavior to linea alba, that could avoid the appearance of short term dehiscences and thus reduce the incidence of incisional hernia. PDXb provides no additional advantages in their behavior regarding PDX suture.

Background: Adhesions commonly appear in patients after abdominal surgery, with considerable individual variation in adhesion composition and severity of the repair process. Here, we address the influence of transforming growth factor (TGF)-β3 and betaglycan in this response, in relation to TGF-β1, in an adhesiogenic rabbit model., Materials and Methods: Omental adhesions were recovered 3, 7, 14, and 90 d after the implantation of a polypropylene mesh on the parietal peritoneum in New Zealand White rabbits. Omentum from nonoperated animals served as control. Tissue specimens were examined for TGF-β3 and TGF-β1 (Western blotting, reverse transcription-polymerase chain reaction), and TGF-β1:TGF-β3 messenger RNA and protein expression ratios were analyzed. Immunohistochemical detection of TGF-β3 and betaglycan was performed., Results: Injury to the omentum led to mobilization of TGF-β3 and betaglycan-expressing cells from milky spots. Fibrous zones in adhesions were simultaneous to the presence of TGF-β1 and the membrane-bound form of betaglycan (7-d adhesions), whereas soluble betaglycan appeared in TGF-β1-positive areas showing limited fibrosis (3-d adhesions). The elevated expression of TGF-β3 concurrent with the presence of membrane-bound form of betaglycan was observed in zones of adipose regeneration (14-d adhesions), whereas zones of fibrous consistency were negative for TGF-β3., Conclusions: Milky spots on the omentum contain inflammatory/immune cells positive for TGF-β3, TGF-β1, and betaglycan, playing a role in the damaged omentum repair. Our observations support the contribution of TGF-β3 to tissue repair through adipose tissue regeneration and the profibrotic role of TGF-β1 and suggest that these effects on the local wound repair response could be driven by the expression of betaglycan in its soluble or membrane-bound form., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The surgical repair of an abdominal wall defect may be complicated by infection. We examined the in vitro and in vivo behavior of Staphylococcus aureus (Sa) and Staphylococcus epidermidis (Se) when placed in contact with three collagen bioprostheses. For the in vitro study, 1 cm(2) fragments of the collagen meshes (Collamend®, Surgisis®, and Permacol®) and a control polytetrafluoroethylene mesh, Preclude®(ePTFE) were incubated on blood agar plates inoculated with Sa or Se. In the in vivo study, 2 partial 3 × 3 cm defects were created in the abdominal wall of 72 rabbits and infected with a suspension-containing 10(6) Colony-forming unit (CFU) of Sa or Se. The defects were then repaired using the above materials. At 14 and 30 days postimplant, mesh specimens were obtained for histological, morphometric, and biomechanical analysis. The incubated collagen meshes showed significantly greater bacterial loads than the ePTFE. In vivo, large abscesses comprised of bacteria (Sa/Se), detritus and white cells could be seen 14 days post-implant. At 30 days, the bacterial infiltrate was reduced in the Se group. In conclusion, in presence of bacterial contamination, no benefits were observed of the use of the collagen bioprostheses tested over the use of a non porous ePTFE mesh (Preclude®)., (Copyright © 2013 Wiley Periodicals, Inc.)

Introduction: The viability and immunological response induced by cryopreserved arterial allografts remain unclear. This study examines the post-graft behaviour of this type of vessel substitute., Materials and Methods: Both iliac arteries were extracted from Lewis rats (donors) and used to establish groups of allogeneic fresh (group I) or cryopreserved (group II) grafts in Fisher-344 rats (recipients). Cryopreserved segments for grafting were prepared by automated controlled freezing at a cooling rate of 1°C/min followed by storage in liquid nitrogen vapour at -145°C for 30 days. Before grafting, the vessels were slowly thawed. Animals were sacrificed at 14, 30, 90 and 180 days post-surgery when graft specimens were obtained for light and electron microscopy and immunohistochemical detection of inflammatory cells (CD45, ED1, CD4, CD8)., Results: After surgery, 85.71% of the grafts in group I and 82.14% in group II were patent. Following long-term implant, both the fresh and cryopreserved allografts showed complete loss of the muscle compartment of the media. Inflammatory or CD45-positive cells (mainly macrophages and CD8 T-lymphocytes) were detected at earlier time points in suture zones and adventitia. In the fresh allografts, the number of immunolabelled cells steadily increased until they were seen to occupy the entire adventitia at 90 days, with high numbers persisting at 6 months. In the cryopreserved allografts, this adventitial inflammatory infiltrate was significantly reduced., Conclusions: The cryopreservation/slow thawing protocol used diminished the immune response induced by fresh arterial allografts improving their behaviour after grafting.

Human umbilical cord Wharton's jelly stem cells (HWJSCs) are gaining attention as a possible clinical source of mesenchymal stem cells for cell therapy and tissue engineering due to their high accessibility, expansion potential, and plasticity. We employed a combination of highly sensitive techniques to determine the average cell viability levels and proliferation capabilities of 10 consecutive cell passages of cultured HWJSCs and then used RNA microarrays to identify genes associated with changes in cell viability levels. We found an initial decrease in cell viability from the first to the third cell passage followed by an increase until the sixth passage and a final decrease from the sixth to tenth cell passages. The highest cell viability levels corresponded to the fifth and sixth passages. The intracellular ionic contents of potassium, sodium, and chlorine suggest that the lower cell viability levels at passages 2, 3, and 8-10 may be associated with apoptotic cell death. In fact, gene expression analysis revealed that the average cell viability was significantly associated with genes with a function in apoptotic cell death, especially pro-apoptotic FASTKD2, BNIP3L genes and anti-apoptotic TNFAIP8 and BCL2L2 genes. This correlation with both pro-apoptotic and anti-apoptotic genes suggests that there may be a complex live-death equilibrium in cultured HWJSCs kept in culture for multiple cell passages. In this study, the highest cell viability levels corresponded to the fifth and sixth HWJSC passages, suggesting that these passages should be preferentially employed in cell therapy or tissue engineering protocols using this cell type.