Circulating myokines IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity

24 p.Objective: To examine the effects of a time-matched endurance versus 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. Methods: 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. Results: 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-15R? concentration (-28% vs. -40%; P=0.023). Finally, in EN2, the delta change of fat mass and IL-6, IL-15 and IL-15R? were associated (r=0.605; r=0.546; r=0.515; P<0.05). IL-13 showed undetected concentrations. Conclusions: 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.Universidad de Alcal

Polymer hernia repair materials: adapting to patient needs and surgical techniques

"Publicación presentada para convocatoria 2023 Proyectos Generación de Conocimiento"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 ccommodate 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, long with their modifications as new surgical techniques have unfolded

Efficacy of antimicrobial agents delivered to hernia meshes using an adaptable thermo-responsive hyaluronic acid-based coating

19 p.Purpose Mesh-related infection is a critical outcome for patients with hernia defect stabilized with synthetic or biological meshes. Even though bioactive meshes loaded with antibiotics or antiseptics are slowly emerging in the market, the available solutions still lack versatility. Here, we proposed a polymer solution, i.e., hyaluronic acid-poly(N-isopropylacrylamide) (HApN), which forms a hydrogel to be used as coating for meshes only when it reaches body temperature. Methods We assessed how the gelation of HApN was influenced by the incorporation of different antibiotic and antiseptic formulations, and how this gel can be used to coat several mesh types. The impact of the coating on the elastic behavior of a macroporous mesh was tested under cyclic elongation condition. Finally, we selected two different coating formulations, one based on antibiotics (gentamicin + rifampicin) and one based on antiseptic (chlorhexidine) and tested in vitro their antimicrobial efficacies. Results HApN can be used as carrier for different antimicrobial agents, without having a strong influence on its gelation behavior. Porous or dense meshes can be coated with this polymer, even though the stability was not optimal on macroporous meshes such as Optilene when pores are too large. HApN loaded with drugs inhibited in vitro the growth of several Gram-positive and Gram-negative bacteria. Conclusion Compared to the available technologies developed to endow meshes with antibacterial activity, the proposed HApN offers further versatility with potential to prevent mesh-related infection in hernioplasty.European Hernia SocietyMinisterio de Ciencia, Innovación y Universidade

The role of the stromal extracellular matrix in the development of pterygium pathology: an update

22 p.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.CIBER-BB

Stromal vascular fraction cells as biologic coating of mesh for hernia repair

11 p.Background. The interest in non-manipulated cells originating from adipose tissue has raised tremendously in the field of tissue engineering and regenerative medicine. The resulting stromal vascular fraction (SVF) cells have been successfully used in numerous clinical applications. The aim of this experimental work is, first to combine a macroporous synthetic mesh with SVF isolated using a mechanical disruption process, and to assess the effect of those cells on the early healing phase of hernia. Methods. Human SVF cells combined with fibrin were used to coat commercial titanized polypropylene meshes. In vitro, viability and growth of the SVF cells were assessed using live/dead staining and scanning electron microscopy. The influence of SVF cells on abdominal wall hernia healing was conducted on immunodeficient rats, with a focus on short-term vascularization and fibrogenesis. Results. Macroporous meshes were easily coated with SVF using a fibrin gel as temporary carrier. The in vitro experiments showed that the whole process including the isolation of human SVF cells and their coating on PP meshes did not impact on the SVF cells? viability and on their capacity to attach and to proliferate. In vivo, the SVF cells were well tolerated by the animals, and coating mesh with SVF resulted in a decrease degree of vascularity compared to control group at day 21. Conclusions. The utilization of SVF-coated mesh influences the level of angiogenesis during the early onset of tissue healing. Further long-term animal experiments are needed to confirm that this effect correlates with a more robust mesh integration compared to non-SVF-coated mesh.European Hernia Society Research GrantTU

Wound Healing Modulation through the Local Application of Powder Collagen-Derived Treatments in an Excisional Cutaneous Murine Model

15 p.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.CIBER-BBNViscofan S.A

New insights into the application of 3D-printing technology in hernia repair.

"Publicación presentada para sexenios"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.Financial support from the CIBER-BB

Experimental study on the use of a chlorhexidine-loaded carboxymethylcellulose gel as antibacterial coating for hernia repair meshes

21 p.Purpose: Biomaterials with an antimicrobial coating could avoid mesh-associated infection following hernia repair. This study assesses the use of a chlorhexidine-loaded carboxymethylcellulose gel in a model of Staphylococcus aureus mesh infection. Methods: A 1% carboxymethylcellulose gel containing 0.05% chlorhexidine was prepared and tested in vitro and in vivo. The in vitro tests were antibacterial activity (S. aureus; agar diffusion test) and gel cytotoxicity compared to aqueous 0.05% chlorhexidine (fibroblasts; alamarBlue). For the in vivo study, partial abdominal wall defects (5 × 2 cm) were created in New Zealand white rabbits (n = 15) and inoculated with 0.25 mL of S. aureus ( 106 CFU/mL). Defects were repaired with a lightweight polypropylene mesh (Optilene) without coating (n = 3) or coated with a carboxymethylcellulose gel (n = 6) or chlorhexidine-loaded carboxymethylcellulose gel (n = 6). Fourteen days after surgery, bacterial adhesion to the implant (sonication, immunohistochemistry), host tissue incorporation (light microscopy) and macrophage reaction (immunohistochemistry) were examined. Results: Carboxymethylcellulose significantly reduced the toxicity of chlorhexidine (p < 0.001) without limiting its antibacterial activity. While control and gel-coated implants were intensely contaminated, the chlorhexidine-gel-coated meses showed a bacteria-free surface, and only one specimen showed infection signs. The macrophage reaction in this last group was reduced compared to the control (p < 0.05) and gel groups. Conclusions: When incorporated in the carboxymethylcellulose gel, chlorhexidine showed reduced toxicity yet maintained its bactericidal effect at the surgery site. Our findings suggest that this antibacterial gel-coated polypropylene meshes for hernia repair prevent bacterial adhesion to the mesh surface and have no detrimental effects on wound repair.Ministerio de Ciencia, Innovación y Universidade

Preclinical bioassay of a novel antibacterial mesh for the repair of abdominal hernia defects

25 p.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 x 2 cm) were created in New Zealand white rabbits (n = 34), the wound inoculated with 0.25 mL of 106 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, rifampicincarboxymethylcellulose 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-touse and effective prophylactic strategy that potentially reduce the prevalence of postoperative mesh infectionMinisterio de Ciencia, Innovación y Universidade

Behaviour at the peritoneal interface of next generation prosthetic materials for hernia repair

22 p.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-?/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.Ministerio de Economía y Competitivida