Cyanoacrylate surgical glue as an alternative to suture threads for mesh fixation in hernia repair.

BACKGROUND: In recent years, the use of synthetic glues has become an established practice in several areas of surgical treatment. For example, they are used in open and laparoscopic surgery and in digestive tract endoscopy, interventional radiology, and vascular neuroradiology. The experiments in this study were aimed at elucidating that suture-based permanent mesh fixation can be replaced by fixation with N-butyl 2-cyanoacrylate glue (Glubran2) for surgical repair of abdominal wall hernias. MATERIALS AND METHODS: In 25 Wistar rats, two hernia defects (1.5 cm in diameter) per animal were created bilaterally in the midline of the abdominal wall. The peritoneum was spared. The lesions were left untreated for 10 d to achieve a chronic condition. Then the defects were covered with TiMESH extralight (2 × 2 cm) and fixed by 30 µL of Glubran2 or traditional suture. The time points of sacrifice were 17 and 28 d, 3, 4, and 5 mo. At autopsy, histology and immunohistochemistry were performed to evaluate the inflammatory response and the presence of apoptotic cells respectively. RESULTS: Mesh fixation was excellent in all samples at each time point. At application sites, the inflammatory reaction was mild with a small number of macrophages and vascularized connective tissue presence around glue and mesh threads. Glue residues were observed in histologic sections at each time point. No presence of apoptotic cells was found. CONCLUSIONS: This study demonstrated that Glubran2 can effectively replace traditional suture in mesh fixation without affecting tissue healing and determining a physiological inflammatory reaction at the abdominal wall site.

Tissue response to poly(ether)urethane-polydimethylsiloxane-fibrin composite scaffolds for controlled delivery of pro-angiogenic growth factors.

The development of a scaffold able to mimic the mechanical properties of elastic tissues and to induce local angiogenesis by controlled release of angiogenic growth factors could be applied in the treatment of several ischemic diseases. For this purpose a composite scaffold made of a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (semi-IPN) and fibrin loaded growth factors (GFs), such as VEGF and bFGF, was manufactured using spray, phase-inversion technique. To evaluate the contribution of each scaffold component with respect to tissue response and in particular to blood vessel formation, three different scaffold formulations were developed as follows: 1) bare PEtU-PDMS; 2) PEtU-PDMS/Fibrin; and 3) PEtU-PDMS/Fibrin + GFs. Scaffolds were characterized in vitro respect to their morphology, VEGF and bFGF release kinetics and bioactivity. The induction of in vivo angiogenesis after subcutaneous and ischemic hind limb scaffold implantation in adult Wistar rats was evaluated at 7 and 14 days by immunohistological analysis (IHA), while Laser Doppler Perfusion Imaging (LDPI) was performed in the hind limbs at 0, 3, 7, 10 and 14 days. IHA of subcutaneously implanted samples showed that at 7 and 14 days the PEtU-PDMS/Fibrin + GFs scaffold induced a statistically significant increase in number of capillaries compared to bare PEtU-PDMS scaffold. IHA of ischemic hind limb showed that at 14 days the capillary number induced by PEtU-PDMS/Fibrin + GFs scaffolds was higher than that of PEtU-PDMS/Fibrin scaffolds. Moreover, at both time-points PEtU-PDMS/Fibrin scaffolds induced a significant increase in number of capillaries compared to bare PEtU-PDMS scaffolds. LDPI showed that at 10 and 14 days the ischemic/non-ischemic blood perfusion ratio was significantly greater in the PEtU-PDMS/Fibrin + GFs than in the other scaffolds. In conclusion, this study showed that the semi-IPN composite scaffold acting as a pro-angiogenic GFs delivery system has therapeutic potential for the local treatment of ischemic tissue and wound healing.

The effect of gamma irradiation on physical-mechanical properties and cytotoxicity of polyurethane-polydimethylsiloxane microfibrillar vascular grafts.

Poly(ether) urethane (PEtU)-polydimethylsiloxane (PDMS) based materials have been processed by a spray, phase-inversion technique to produce microfibrillar small-diameter vascular grafts; however the effect of sterilization upon these grafts is still unknown. This study investigated the effect of gamma irradiation on grafts made of PEtU-PDMS materials containing different PDMS concentrations. Sterilisation-induced changes in surface chemical structure and morphology were assessed by infrared spectroscopy, light and scanning electron microscopy. Tensile tests were used to examine changes in mechanical properties and the cytotoxicity evaluation was performed on L929 fibroblasts. The study demonstrated that physical-chemical and mechanical properties of PEtU-PDMS grafts, at each PDMS concentration, were not significantly affected by the exposure to gamma irradiation, moreover no sign of cytotoxicity was observed after sterilisation. Although in vitro experiments have been promising, further in vivo studies are necessary to evaluate the biodegradation behaviour of PEtU-PDMS graft after gamma irradiation, before any clinical application.

Long term performance of small-diameter vascular grafts made of a poly(ether)urethane-polydimethylsiloxane semi-interpenetrating polymeric network.

In the past years considerable research efforts have been directed at developing more suitable synthetic vascular grafts, but small-diameter vascular grafts (SDVGs) perform less well than autogenous arterial or venous grafts. Grafts such as Dacron and ePTFE have often been used as alternatives to autologous grafts, but they have shown poor patency rates when used in small-diameter sizes or low-flow locations. Nevertheless, despite these efforts no alternative concepts have emerged yet that promises to replace the current generation of synthetic grafts soon. The purpose of this preliminary in vivo study was to assess the blood and tissue compatibility behaviors of a novel compliant SDVGs, fabricated with a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (semi-IPN) and featuring two different porous layers in the wall thickness. Grafts were implanted according to anastomotic techniques which emulate the flow conditions clinically adopted for peripheral or aorto-coronary bypass procedures. Relatively long grafts were implanted in the common carotid artery of adult sheep and compared to standard ePTFE grafts of the same size and length implanted controlaterally. The animal experimentation showed superior handling and compliance characteristics, and patency rates of PEtU-PDMS grafts in comparison with a standard ePTFE graft, and the ability of remodelling in vivo while being gradually replaced by a natural tissue with no sign of calcification.

A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors.

The aim of this study was to fabricate and characterize in vitro a novel composite scaffold that, combining good mechanical properties with a controlled and sustained release of bioactive pro-angiogenetic growth factors, should be useful for angiogenesis induction in organs/tissues in which is also necessary to give resistance and mechanical strength. Composite scaffolds, constituted by a synthetic biocompatible material, a poly(ether)urethane-polydimethylsiloxane blend, and a biological polymer, the fibrin, were manufactured by spray, phase-inversion technique. During the manufacturing process heparin and heparin-binding growth factors, such as VEGF(165) and bFGF, were incorporated into the fibrin layer. Microscopical examinations showed a homogeneous fibrin layer firmly adherent on top of the synthetic material. Tensile tests highlighted the high elasticity of the composite scaffold and its capability to maintain integrity up to high deformation. VEGF(165) and bFGF release were controlled by fibrinogen concentration, whereas it was not affected by heparin concentration, as revealed by ELISA assay. The biological activity of the released growth factors was maintained as demonstrated by HUVEC proliferation. Finally, scaffolds induced a low monocyte mRNA expression of inflammatory markers (IL-8, L-SEL, LFA-1 and iNOS). In conclusion, the new composite scaffolds, once implanted, providing a co-localization and temporal distribution of bioactive VEGF and bFGF in addition to good mechanical properties, may be useful to stimulate new vessels formation in ischemic tissues.

Glubran2 surgical glue: in vitro evaluation of adhesive and mechanical properties.

BACKGROUND: In surgical and endoscopic procedures, tissue adhesives are commonly used as reinforcement of sutures or as bonding and hemostatic agents. Fibrin glues do not guarantee adequate properties for many clinical applications; on the contrary, cyanoacrylate glues guarantee high bonding strength between biologic tissues. The aim of this study was to provide evidence regarding adhesive and strength properties of a widely used cyanoacrylate glue, Glubran2, GEM s.r.l., Viareggio, Italy. Comparative tests were also carried out on a commercial fibrin glue. MATERIAL AND METHODS: Glubran2 is a modified n-butyl-2-cyanoacrylate glue approved for internal and external use, in Europe. The glue, on contact with living tissues polymerizes rapidly, generating a film that guarantees firm adherence of tissues. In this study, adhesive properties on biologic substrates, both of Glubran2 and of fibrin glue, were investigated according to American Society for Testing and Materials (ASTM) standards, while their strength, after polymerization on an inert substrate, was investigated according to Deutsches Institut Für Normung (DIN) standards. RESULTS: All tests evidenced a strong bonding capability of Glubran2 on biologic tissues and high tensile strength of polymerized film; high breaking strength of polymerized glue was highlighted by tensile tests. CONCLUSION: The present study fills the gap concerning Glubran2 adhesive and tensile properties. All tests showed the intrinsic tensile strength of polymerized Glubran2 and its capability to realize a higher-resistance bonding among biologic tissues, in comparison with fibrin glue, giving strong indication of its usefulness in surgical and endoscopic practice, especially in a wet environment.

PDMS content affects in vitro hemocompatibility of synthetic vascular grafts.

An unsolved problem when employing small-diameter vascular grafts for aorto-coronary by-pass and peripheral reconstruction is the early thrombotic occlusion. The PEtU-PDMS is a new elastomeric material, composed of poly(ether)urethane and polydimethylsiloxane, synthesized to realize grafts with improved hemocompatibility characteristics. In order to investigate the effect of PDMS content on hemocompatibility, three different percentages of PDMS containing grafts (10, 25 and 40) were evaluated. Grafts realized with Estane 5714-F1 and silicone medical grade tubes were used as references. The hemocompatibility was investigated by an in vitro circuit in which human anticoagulated blood was circulated into grafts by a peristaltic pump modified to obtain a passive flow. For each experiment, 40 cm length graft was closed into a circular loop and put in rotation for 2 h at 37 degrees C. At the end of the experiments different parameters regarding platelet adhesion and activation were evaluated: circulating platelets count, beta-thromboglobulin release, platelet CD62P expression and amount of monocyte-platelet conjugates. PEtU-PDMS grafts with 25 and 40% of PDMS induced the lowest platelet adhesion, plasma level of beta-TG and amount of monocyte-platelet conjugates. No significative variations were observed in CD62P expression. In conclusion, PDMS content significatively affects blood-graft surface interaction, in fact higher PDMS percentage containing grafts showed the best in vitro hemocompatibility.