Natalio García-Honduvilla

Comparing the Behavior of Different Polypropylene Meshes (Heavy and Lightweight) in an Experimental Model of Ventral Hernia Repair

New generation prosthetic biomaterials for abdominal wall repair have been designed to be less dense, by having larger pores than that of the standard polypropylene meshes, to improve abdominal wall compliance. The aim of the present study was to analyze the functional and morphologic properties of these new meshes. For this purpose, 7 x 5 cm(2) defects were created in the anterior abdominal wall of 36 male New Zealand White rabbits and repaired using different polypropylene meshes: a heavyweight mesh (HW), Surgipro, and two lightweight meshes (LW), Parietene and Optilene. Six animals each implanted with biomaterial were sacrificed on postoperative days 14 and 90. Histological and morphometric analysis, adhesion assessment, and biomechanical resistance tests were performed. Similar behavior was shown by the LW and HW meshes in terms of the adhesions and macrophage response induced. After 14 days, the tensile strength of Optilene was greater than the strengths recorded for the other two biomaterials, probably because of its high elasticity. By 90 days, however, the tensile strengths of the three biomaterials were comparable. In conclusion, despite an initial tensile strength advantage shown by the mesh with larger pores, at 90 days postimplant, tensile strengths were similar. Compared with HW, LW prostheses have the benefit that less foreign material was implanted, preserving the elasticity of the recipient host tissue.

Postimplant behavior of lightweight polypropylene meshes in an experimental model of abdominal hernia.

Background. Over the years, reticular prostheses have undergone changes in their structure and composition to give rise to todays partially absorbable lightweight meshes. This study was designed to assess the biological and biomechanical behavior of these prostheses to establish whether they offer any advantages over nonabsorbable lightweight polypropylene prostheses. Materials and Methods. 7 × 5 cm defects were created in the anterior abdominal wall of New Zealand White rabbits and repaired by securing different prostheses to the edges of the defect with a running 4/0 polypropylene suture. The lightweight biomaterials compared were two nonabsorbable meshes: Parietene® and Optilene elastic®, and two partially absorbable prostheses: Vypro II® and Ultrapro®. At 14 and 90 days postimplant, tissue/prosthesis specimens were subjected to histological, immunohistochemical, shrinkage, and biomechanical analyses. Results. Adhesion formation on the peritoneum-facing surface of the meshes was significantly less extensive in the meshes with absorbable components at 90 days postimplant. The newly formed tissue around the prosthetic filaments was comprised of collagen fibers, fibroblasts, blood vessels, and macrophages. The partially absorbable meshes showed higher macrophage proportions (due to remnants of absorbable material and their structure) than the nonabsorbable meshes at 90 days, although differences were not significant. At 90 days postimplant, similar tensile strengths were recorded for all the implants. Conclusions. All the prosthetic materials induced good host tissue ingrowth, with no significant differences in tensile strength observed. Our findings suggest that partially absorbable lightweight prostheses could offer advantages over nonabsorbable lightweight meshes since less foreign material persists in the recipient, improving abdominal wall compliance.

Bioactive bilayered dressing for compromised epidermal tissue regeneration with sequential activity of complementary agents

The article deals with the design, preparation, and evaluation of a new bilayered dressing for application in the healing of compromised wounds. The system is based on the sequential release of two complementary bioactive components to enhance the activation of the regeneration of dermal tissue. The internal layer is a highly hydrophilic and biodegradable film of gelatin and hyaluronic acid (HG), crosslinked with the natural compound genipin, which reacts with the amine groups of gelatin. This film is loaded with the proangiogenic, anti-inflammatory, and antibacterial peptide, proadrenomedullin N-terminal 20 peptide (PAMP), that is released slowly in the wound site. The external layer, more stable and less hydrophilic, is constituted by a biodegradable polyurethane derived from poly(caprolactone) and pluronic L61. This layer is loaded with resorbable nanoparticles of bemiparin (a fractionated low molecular weight heparin), which promotes the activation of growth factors, FGF and VEGF, and provides a good biomechanical stability and controlled permeability of the bilayered dressing. Experiments carried out in mice demonstrate the excellent angiogenic effect of the HG film in the dermal tissue. Application of the bilayered dressing in the wound healing rabbit ear model shows an improved cicatrization of the wound in both ischemic and non-ischemic defects, favoring epithelialization and reducing noticeably the contraction and the inflammation.

Efficiency of 4% Icodextrin in Preventing Adhesions to Spiral Tacks Used to Fix Intraperitoneal Prostheses

Background/Aims: This study was designed to evaluate the extent of adhesion formation to prostheses fixed with spiral tacks and to establish whether the use of Ringer’s lactate or icodextrin could prevent these adhesions. Methods:24New Zealand white rabbits weighing around 3,000 g were implanted with a 7 × 5 cm patch of ePTFE (DualMesh®) through amidline laparotomy. The prosthesis was fixed to the intact peritoneum using spiral tacks. Three study groups were established according to whether the animals were: implanted with ePTFE fixed with spiral tacks or implanted with ePTFE fixed with spiral tacks and simultaneously administered Ringer’s lactate or 4% icodextrin in the peritoneal cavity. Adhesion formation and prosthetic behavior at the prosthesis/peritoneal interface were evaluated and quantified by sequential laparoscopy performed at 3, 7 and 14 days. Results: Adhesions generally formed on the tacks and were classified as the fully integrated type. No significant differences were observed in terms of the extent of adhesions or of neoperitoneal thickness between control animals and those receiving Ringer’s lactate or icodextrin. Conclusions: (a)Prosthesis-fixing tacks induced adhesions; (b) the use of substances such as icodextrin or Ringer’s lactate does not seem to diminish adhesion formation, and (c) the use of icodextrin offered no benefits over that of Ringer’s lactate solution.

A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats

Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show deficient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in fibroblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3-10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on fibroblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisation and fibrosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administration vehicle for hGH improves the wound scarring process in the pathological setting of diabetes.

Effects of a novel NADPH oxidase inhibitor (S42909) on wound healing in an experimental ischemic excisional skin model.

Chronic wounds are a serious healthcare problem. As non‐healing wounds involve continuous pathologic inflammatory stage, research is focused on anti‐inflammatory treatments. Our objective was to analyze the effect of S42909, a potent NADPH oxidase inhibitor activity, with vascular anti‐inflammatory properties. An ischemic rabbit ear ulcer model (24 New Zealand white rabbits) was used to evaluate the reepithelialization/contraction areas, anti‐/pro‐inflammatory cytokines mRNA (TGF‐β1/IL‐10/IFN‐γ/VEGF) by qRT‐PCR, collagen I/III deposition, and neovascularization (TGF‐β1/VEGF) by morphological and immunohistochemical analyses. Three different doses were administered by gavage for 2 weeks: 10 and 30 mg/kg/d in self‐microemulsion drug delivery system (SMEDDS) and 100 mg/kg/d in arabic gum. Each vehicle was used as control. No signs of infection or necrosis were found. Reepithelialization was almost complete whatever the groups reaching 95% at the dose of 100 mg/kg. Wound contraction was significantly reduced in all S42909‐treated groups. A significant increase in anti‐inflammatory cytokines TGF‐β1 mRNA and IL‐10 mRNA was observed at the dose of 100 and 30 mg/kg/d, respectively. No changes were observed in pro‐inflammatory factors INF‐γ and VEGF mRNA. Ischemic skin wound areas had scarce expression of collagen I/III and showed rich glycosaminoglycans content. Treatment increased the collagen deposition and TGF‐β1 protein expression and decreased glycosaminoglycan content dose dependently; however, no effect in VEGF was appreciated. Therefore, our results indicate that S42909 improved healing process by dampening excessive inflammation and facilitating collagen deposition without wound contraction phenomena. S42909 might be a promising therapy to treat chronic wounds as venous leg ulcers.

3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine

The current study reports on the manufacturing by rapid prototyping technique of three-dimensional (3D) scaffolds based on silicon substituted hydroxyapatite with Elastin-like Recombinamers (ELRs) functionalized surfaces. Silicon doped hydroxyapatite (Si-HA), with Ca10(PO4)5.7(SiO4)0.3(OH)1.7h0.3 nominal formula, was surface functionalized with two different types of polymers designed by genetic engineering: ELR-RGD that contain cell attachment specific sequences and ELR-SNA15/RGD with both hydroxyapatite and cells domains that interact with the inorganic phase and with the cells, respectively. These hybrid materials were subjected to in vitro assays in order to clarify if the ELRs coating improved the well-known biocompatible and bone regeneration properties of calcium phosphates materials. The in vitro tests showed that there was a total and homogeneous colonization of the 3D scaffolds by Bone marrow Mesenchymal Stromal Cells (BMSCs). In addition, the BMSCs were viable and able to proliferate and differentiate into osteoblasts.nnnSTATEMENT OF SIGNIFICANCEnBone tissue engineering is an area of increasing interest because its main applications are directly related to the rising life expectancy of the population, which promotes higher rates of several bone pathologies, so innovative strategies are needed for bone tissue regeneration therapies. Here we use the rapid prototyping technology to allow moulding ceramic 3D scaffolds and we use different bio-polymers for the functionalization of their surfaces in order to enhance the biological response. Combining the ceramic material (silicon doped hydroxyapatite, Si-HA) and the Elastin like Recombinamers (ELRs) polymers with the presence of the integrin-mediate adhesion domain alone or in combination with SNA15 peptide that possess high affinity for hydroxyapatite, provided an improved Bone marrow Mesenchymal Stromal Cells (BMSCs) differentiation into osteoblastic linkage.

Elastin Development-Associated Extracellular Matrix Constituents of Subepithelial Connective Tissue in Human Pterygium

PURPOSEnWe evaluated the expression of several extracellular matrix constituents implicated in the synthesis and reticulation of elastin in human pterygium, according to age and sex of the patients.nnnMETHODSnPterygia and normal conjunctiva samples were divided into groups according to age (<50/≥50 years) and sex. Tissue was subjected to immunohistochemical staining with anti-lysyl oxidase (LOX), lyxyl oxidase-like 1 (LOXL-1), fibulin (FBLN)-5 and FBLN4, and fibrillin-1 (FBN1) antibodies. Specific primers for the same constituents were used in a quantitative real-time PCR (qRT-PCR) analysis to determine gene expression.nnnRESULTSnThe LOXL-1 (P = 0.0002), FBLN5 (P = 0.0035), and FBN1 (P < 0.0001) mRNAs were significantly higher in pterygium than conjunctiva. No differences were found for LOX and FBLN4 mRNA. The expression of LOXL-1 was not affected by age or sex; however, pterygium from men and patients over 50 years old exhibited significantly higher FBLN5/FBN1 expression than did controls. The LOX gene expression was higher in the pathologic samples from the over 50-year-olds compared to the conjunctiva (P = 0.0396) and in mens versus womens pterygium (P = 0.0173). In general, the levels of LOX, LOXL-1, and FBLN5 decreased with age in healthy samples, while the pathology seemed to have increased expression of the three proteins, and even more so in older patients. The FBLN4 and FBN1 immunostaining was slight in all samples, displaying no differences between groups.nnnCONCLUSIONSnSeveral extracellular matrix constituents, LOXs, FBN1, and FBLN5, implicated in the development of elastin, are overexpressed in the subepithelial connective tissue extracellular matrix of human pterygium, supporting our hypothesis that elastic synthesis and reticulation is dysregulated in this type of pathology.

Serum IL-15 and IL-15Rα levels are decreased in lean and obese physically active humans

Circulating IL‐15 presence is required to stimulate anti‐adipogenic effects of the IL‐15/IL‐15Rα axis in adipose tissue. Although exercise increases blood IL‐15 expression post‐exercise, it remains inconclusive whether physical activity can alter the baseline concentrations of this cytokine. The aim of this study was to determine whether physical activity regulates circulating IL‐15 and IL‐15Rα in lean and obese individuals. Two hundred and seventy‐six participants were divided into five groups according to physical activity (PA), body mass and type 2 diabetes mellitus (T2DM) diagnosis: (a) lean PA (N = 25); (b) lean non‐PA (N = 28); (c) obese PA (N = 64); (d) obese non‐PA (N = 79); and (e) obese non‐PA with T2DM (N = 80). Serum IL‐15 and IL‐15Rα, blood glucose/lipid profile and body composition were measured. Serum IL‐15 and IL‐15Rα decreased in PA participants compared to non‐PA (P < .05), while IL‐15 and IL‐15Rα increased in obese with T2DM compared to obese without T2DM (P < .05). No differences were observed between lean non‐PA and obese PA. Serum IL‐15Rα was associated with fasting glucose (R2 = .063), insulin (R2 = .082), HbA1c (R2 = .108), and HOMA (R2 = .057) in obese participants. Circulating IL‐15 and IL‐15Rα are reduced in lean and obese participants who perform physical activity regularly (≥180 min/week), suggesting a regulative role of physical activity on the circulating concentrations of IL‐15 and IL‐15Rα at baseline. Moreover, the relationship observed between IL‐15Rα and glucose profile may indicate a role of the alpha receptor in glucose metabolism.