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

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.

Mesh Fixation Using a Cyanoacrylate Applied as a Spray Improves Abdominal Wall Tissue Repair.

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.

Comparing the influence of two immunosuppressants (fingolimod, azathioprine) on wound healing in a rat model of primary and secondary intention wound closure.

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).

Sutures versus new cyanoacrylates in prosthetic abdominal wall repair: a preclinical long-term study.

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.

Behavior of a new long-chain cyanoacrylate tissue adhesive used for mesh fixation in hernia repair.

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.

Host tissue response by the expression of collagen to cyanoacrylate adhesives used in implant fixation for abdominal hernia repair.

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.

Remodeling of Noncrosslinked Acellular Dermal Matrices in a Rabbit Model of Ventral Hernia Repair.

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.

Comparing the host tissue response and peritoneal behavior of composite meshes used for ventral hernia repair.

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.

Involvement of transforming growth factor-ß3 and betaglycan in the cytoarchitecture of postoperative omental adhesions.

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)-ß3 and betaglycan in this response, in relation to TGF-ß1, 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-ß3 and TGF-ß1 (Western blotting, reverse transcription-polymerase chain reaction), and TGF-ß1:TGF-ß3 messenger RNA and protein expression ratios were analyzed. Immunohistochemical detection of TGF-ß3 and betaglycan was performed. RESULTS: Injury to the omentum led to mobilization of TGF-ß3 and betaglycan-expressing cells from milky spots. Fibrous zones in adhesions were simultaneous to the presence of TGF-ß1 and the membrane-bound form of betaglycan (7-d adhesions), whereas soluble betaglycan appeared in TGF-ß1-positive areas showing limited fibrosis (3-d adhesions). The elevated expression of TGF-ß3 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-ß3. CONCLUSIONS: Milky spots on the omentum contain inflammatory/immune cells positive for TGF-ß3, TGF-ß1, and betaglycan, playing a role in the damaged omentum repair. Our observations support the contribution of TGF-ß3 to tissue repair through adipose tissue regeneration and the profibrotic role of TGF-ß1 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.

New suture materials for midline laparotomy closure: an experimental study.

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.

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

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.

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

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.

Self-adhesive hydrogel meshes reduce tissue incorporation and mechanical behavior versus microgrips self-fixation: a preclinical study.

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.

Polymer Hernia Repair Materials: Adapting to Patient Needs and Surgical Techniques.

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.

Antibacterial polypropylene mesh fixation with a cyanoacrylate adhesive improves its response to infection.

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.

Antibacterial Biopolymer Gel Coating on Meshes Used for Abdominal Hernia Repair Promotes Effective Wound Repair in the Presence of Infection.

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.

New Insights into the Application of 3D-Printing Technology in Hernia Repair.

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.

The Role of the Stromal Extracellular Matrix in the Development of Pterygium Pathology: An Update.

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.

Transdifferentiation potentiality of human Wharton's jelly stem cells towards vascular endothelial cells.

Human Wharton's jelly stem cells (HWJSC) emerged as a potential source of viable cells for use in tissue engineering. In this work, we have analyzed the transdifferentiation capabilities of HWJSC towards transdifferentiated endothelial-like cells (Tr-ELC) in order to establish the potential usefulness of these cells in vascular tissue engineering. Our results show that Tr-ELC became more polygonal and less proliferative than HWJSC, resembling the structure and proliferation rate of the endothelial cells. In addition, the markers of mesenchymal undifferentiation CD9, E-cad, PODXL, and SSEA-4 are downregulated in Tr-ELC, suggesting that these cells can be in the process of adult differentiation. Besides, RT-PCR and microarray analyses revealed that some genes with a role in defining the endothelial phenotype and structure are upregulated (VEGF-R1, EDF1, AAMP, CD31, CD34, CDH5, and ICAM2) or downregulated (VEGF) in Tr-ELC, although a number of genes related to relevant endothelial cell functions (CD36, ECE2, VWF, THBD, PGI2, ECE1, and ACE) did not change or were only partially induced. All this implies that HWJSC are able to efficiently transdifferentiate towards Tr-ELC at the phenotypical level following a hierarchical pattern of gene activation, with an earlier induction of morphological and phenotypical genes.

Thermo-Responsive Antimicrobial Hydrogel for the In-Situ Coating of Mesh 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 (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.