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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.
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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.
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Hérnia Abdominal , Telas Cirúrgicas , Adesivos , Animais , Cianoacrilatos , Hérnia Abdominal/cirurgia , Herniorrafia , Humanos , Hidrogéis , Polipropilenos , Coelhos , Cimentos de ResinaRESUMO
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.
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Herniorrafia , Telas Cirúrgicas , Animais , Materiais Biocompatíveis , Peritônio/cirurgia , Polipropilenos , Coelhos , Aderências TeciduaisRESUMO
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.
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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.
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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.
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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.
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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 106 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.
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Antibacterianos/administração & dosagem , Clorexidina/administração & dosagem , Hérnia Abdominal/cirurgia , Herniorrafia/instrumentação , Telas Cirúrgicas , Infecção da Ferida Cirúrgica/prevenção & controle , Animais , Cianoacrilatos , Modelos Animais de Doenças , Hérnia Abdominal/etiologia , Herniorrafia/efeitos adversos , Masculino , Polipropilenos , Coelhos , Infecção da Ferida Cirúrgica/etiologia , Adesivos TeciduaisRESUMO
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 (106 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.
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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 (106 CFU), for two study groups-unloaded (n = 4) and 0.1 mg/cm2 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.
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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 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, 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.
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Antibacterianos/administração & dosagem , Antibioticoprofilaxia/instrumentação , Hérnia Abdominal/cirurgia , Herniorrafia/efeitos adversos , Telas Cirúrgicas , Infecção da Ferida Cirúrgica/prevenção & controle , Animais , Carboximetilcelulose Sódica/administração & dosagem , Modelos Animais de Doenças , Herniorrafia/instrumentação , Herniorrafia/métodos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Coelhos , Rifampina/administração & dosagem , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Infecção da Ferida Cirúrgica/microbiologiaRESUMO
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.
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Cianoacrilatos/administração & dosagem , Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Procedimentos Cirúrgicos sem Sutura/métodos , Adesivos Teciduais/administração & dosagem , Parede Abdominal/cirurgia , Animais , Modelos Animais de Doenças , Herniorrafia/instrumentação , Coelhos , Telas Cirúrgicas , Procedimentos Cirúrgicos sem Sutura/instrumentação , Suturas , Resistência à TraçãoRESUMO
INTRODUCTION: Pterygium is a conjunctival fibrovascular tissue growth on the cornea. The pathogenesis of pterygium involves several factors such as the presence of active angiogenic factors. Expansion of the lymphatic microvasculature has also been hypothesized. This study examines the activity of the angiogenic/lymphangiogenic factor VEGF and the expression of vascular and lymphatic endothelial proteins in pterygia and normal conjunctival tissues. MATERIAL AND METHODS: Primary grade 2 pterygium (n=20) and normal conjunctiva (n=20) biopsies were obtained during surgery after written informed consent. mRNA expression for CD31, podoplanin, and VEGF (isoforms VEGF-A and VEGF-165) were determined by qRT-PCR. Tissue samples were also processed for immunohistochemical techniques to examine the lymphatic and vascular endothelium (anti-D2-40, anti-CD31 respectively) and VEGF-A and VEGF-C levels and distribution. RESULTS: VEGF-A gene expression levels failed to differ between the healthy and pterygium tissues. However, expression of its more angiogenic isoform, VEGF-165, was significantly higher in the pterygia. Immunohistochemistry revealed the greater presence of VEGF-A, compared to VEGF-C, in pterygium than conjunctiva, both in blood vessels and extracellular matrix. In addition, pterygia showed higher expression levels of the endothelial junction protein CD31. Lymphatic marker D2-40 expression was slightly augmented in this pathological tissue. The ratio between blood and lymphatic vessel counts was 1.05 in the normal conjunctiva and 3-fold this value in pterygium. CONCLUSION: In pterygium, while both lymphangiogenesis and angiogenesis take place, the formation of new blood vessels is the most relevant event, correlating with the increased expression of vascular endothelial CD31 and an elevated blood/lymphatic vessel ratio. The presence of high levels of VEGF-A in both vessel networks and extracellular matrix in human pterygium tissue may have a major impact on angiogenesis in this pathological tissue.
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Túnica Conjuntiva/anormalidades , Linfangiogênese , Neovascularização Patológica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Pterígio/metabolismo , Fatores de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Túnica Conjuntiva/irrigação sanguínea , Túnica Conjuntiva/metabolismo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
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.
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Colágeno Tipo III/genética , Hérnia Abdominal/cirurgia , Herniorrafia/instrumentação , Aderências Teciduais/metabolismo , Animais , Colágeno Tipo III/metabolismo , Modelos Animais de Doenças , Hérnia Abdominal/metabolismo , Humanos , Laparoscopia , Polipropilenos/química , Polivinil/química , Coelhos , Telas Cirúrgicas , Aderências Teciduais/genética , Titânio/químicaRESUMO
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).
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Azatioprina/farmacologia , Cloridrato de Fingolimode/farmacologia , Imunossupressores/farmacologia , Inflamação/tratamento farmacológico , Técnicas de Fechamento de Ferimentos , Cicatrização/efeitos dos fármacos , Animais , Inflamação/patologia , Masculino , Modelos Animais , Ratos , Ratos Sprague-DawleyRESUMO
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.
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Cianoacrilatos , Herniorrafia , Polipropilenos , Telas Cirúrgicas , Adesivos , Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Reação a Corpo Estranho/patologia , Macrófagos , Teste de Materiais , Coelhos , SuturasRESUMO
In chronic venous insufficiency of the lower limbs, data show that the clinical manifestation is varicose veins (VVs), and VV epidemiology suggests that sex hormones directly influence disease development through intracellular receptors. This study aimed to determine the presence and localization of oestrogen receptors (ERs), progesterone receptors (PRs), and androgen receptors (ARs) in both healthy and VV wall cells and their relationship with gender. In this study, samples from patients without a history of venous disease (CV) (n = 18) and with VV (n = 40) were used. The samples were divided by gender: CV women (CVw) = 6, CV men (CVm) = 12, VV women (VVw) = 25, and VV men (VVm) = 15. RT-qPCR and immunohistochemical techniques were performed, and increased ER and PR protein expression was found in VVw in all tunica layers. ARs were localized to the adventitial layer in the CV and were found in the neointima in VVs. mRNA expression was increased for ER and PR in VVw. AR gene expression was significantly decreased in VVm. The increase in the number of these receptors and their redistribution through the wall reinforces the role of sex hormones in varicose vein development.
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Pré-Menopausa/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Varizes/metabolismo , Varizes/fisiopatologia , Remodelação Vascular , Adulto , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Varizes/genéticaRESUMO
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.
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Cianoacrilatos/uso terapêutico , Hérnia Abdominal/cirurgia , Herniorrafia/instrumentação , Suturas , Animais , Fenômenos Biomecânicos , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Cianoacrilatos/efeitos adversos , Cianoacrilatos/química , Modelos Animais de Doenças , Macrófagos/imunologia , Masculino , Coelhos , Telas CirúrgicasRESUMO
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.
Assuntos
Parede Abdominal/patologia , Cicatrização , Animais , Materiais Biocompatíveis , Fenômenos Biomecânicos , Modelos Animais de Doenças , Implantes Experimentais , CoelhosRESUMO
PURPOSE: To assess the feasibility of characterizing and following up the mechanical behavior of the corneal tissue after corneal cross-linking (CXL) by using a combined mechanical (in vivo indentation and in vitro uniaxial tensile tests) and morphological (immunohisto-chemistry) experimental protocol. METHODS: CXL (3 mW/cm2; 370 nm) for 20 minutes (total dose 3.6 J/cm2) was performed on 12 New Zealand rabbits. The mechanical behavior of the cornea was characterized in small and large strain regimens using an in vivo indentation test with a laboratory device and an in vitro uniaxial tensile test, respectively. These tests and corneal immunohistochemistry were performed before (PreCXL) and on the 7th (PostCXL-7d) and 56th days (PostCXL-56d) after CXL. The intraocular pressure and corneal thickness were measured before each test. RESULTS: For the indentation tests, significant differences were found between PreCXL and PostCXL-7d and between PostCXL-7d and PostCXL-56d, but not between PreCXL and PostCXL-56d. On average, for the small strain regimen, PostCXL-7d corneas showed the most compliant behavior, with progressive recovery of the corneal stiffness over time. For the large strain regimen, significant differences in the maximum tangent modulus between PreCXL and PostCXL-7d and between PreCXL and PostCXL-56d were observed for the uniaxial tensile tests, with no significant differences between PostCXL-7d and PostCXL-56d. Immunohistochemistry showed a lack of cells in the anterior stroma at PostCXL-7d, but at PostCXL-56d the cell density and morphology were comparable to PreCXL. CONCLUSIONS: Indentation tests cannot characterize the changes in the corneal collagen scaffold caused by the CXL, but the uniaxial test can. However, indentation tests can assess the recovery of keratocyte density after CXL. [J Refract Surg. 2017;33(3):184-192.].