Association of systemic antibody response against polyethylene terephthalate with inflammatory serum cytokine profile following implantation of differently coated vascular prostheses in a rat animal model.

Experimental studies demonstrated antibodies against matrix and coating of polyester-based vascular prostheses. Thus, this study examined associations of these antibodies with serum cytokines (IL-2, IL-4, and IL-10) and local inflammatory reactions. Rats (n = 8/group) intramuscularly received prosthesis segments [PET-C, PET-G, and PET-A groups: polyethylene terephthalate (PET)-based prostheses coated with bovine collagen and gelatin or human serum albumin, respectively; uncoated polytetrafluoroethylene-based (PTFE) prosthesis], with sham-operated controls. Blood was drawn pre-operatively and weekly until day 22. Polymer-specific or coating-specific antibodies and cytokines were detected by enzyme immunoassays, inflammatory reactions were immunohistochemically evaluated on day 23. Polymer-specific antibodies were detected in all PET-groups using uncoated PET as antigenic target, but not for PTFE or controls, coating-specific antibodies only for PET-A. IL-10 was increased in all PET-groups and correlated with polymer-specific antibodies for PET-G and PET-A. IL-2 was increased for PET-A, but overall correlated with PET-specific antibodies. IL-4 remained unchanged in all groups. Intense local inflammatory reactions (ED1+ /ED2+ macrophages and T lymphocytes) were found within all PET-groups, but only minor for PTFE or controls. In conclusion, PET-specific antibodies were associated with increased IL-10 and along with concurrent coating-specific antibodies also with increased IL-2, indicating a specific T cell response. Thus, matrix and/or coating of polymeric vascular prostheses elicit distinct systemic immune reactions, probably influencing local inflammatory reactions.

Corrigendum to 'In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats'.

In the "Materials and methods" chapter of the article given above, in section 2.1 titled "Implant samples and preparation" on page 2 (top paragraph of the right column), an incorrect value of 1 µg mm-2 for the average Cu load of the surface was inadvertently specified. This was due to an accidental mix-up of electronic data sets from examination of different implant series. The correct value is 0.2 µg mm-2. No other data given in the article are affected. The authors kindly apologize for this mistake.

In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats.

Copper (Cu) based coatings can reduce infections for titanium (Ti) implants. However, Cu is also cytotoxic. To examine the balance of antibacterial versus adverse tissue effects, this study aimed at evaluating a Cu coating regarding in vivo Cu release and local inflammatory reactions for 72 h. TiAl6V4 plates received either plasma electrolytic oxidation only (Ti), or an additional galvanic Cu deposition (Ti-Cu). No Staphylococcus aureus were found in vitro on Ti-Cu after 24 h. Following simultaneous intramuscular implantation of two Ti and two Ti-Cu plates into nine rats, serum Cu was elevated until 48 h and residual Cu on explanted samples reduced accordingly after 48 h. Total and tissue macrophages around implants increased until 72 h for both series, and were increased for Ti-Cu. As numbers of total and tissue macrophages were comparable, macrophages were probably tissue-derived. MHC-class-II-positive cells increased for Ti-Cu only. T-lymphocytes had considerably lower numbers than macrophages, did not increase or differ between both series, and thus had minor importance. Tissue reactions increased beyond Cu release, indicating effects of either surface-bound Cu or more likely the implants themselves. Altogether, Ti-Cu samples possessed antibacterial effectiveness in vitro, released measurable Cu amounts in vivo and caused a moderately increased local inflammatory response, demonstrating anti-infective potential of Cu coatings.

Improved laparoscopic treatment of symptomatic urachal anomalies.

PURPOSE: Remaining urachal anomalies are seldom found but can result in long-standing recurrent symptoms and repeated surgery. In this single-centre study, we evaluated the laparoscopic approach of excision of the urachus leaving the umbilicus untouched. METHODS: Twenty-one patients were operated on for persisting symptomatic urachal anomalies between 1998 and 2011. Patients included 8 males and 13 females (mean 28.5 years, range 15-72 years). Patients' histories, surgical data and demographic data were prospectively collected and analysed. During follow-up, patients were evaluated using the total body image and cosmesis questionnaire (BIQ). RESULTS: Excision of the urachus was carried out in 18 cases in a laparoscopic three-trocar technique and in 3 cases using single-site surgery. In all cases, the infected umbilicus was left untouched. Mean surgical time of all procedures was 55.7 min (31-106 min). Histopathology confirmed an urachal anomaly in all cases. The former discharging or infected umbilicus healed without any complications. Sixteen patients could be included for the BIQ. Total body image score after surgery was 5.49 with a score of 5.0 being the most satisfactory result possible. The total cosmetic score was 21.37 close to the maximum score of 24. CONCLUSIONS: The laparoscopic treatment of urachal anomalies using a three-trocar technique or the single-site surgery technique is both safe and effective. In our opinion, the excision of the umbilicus should be avoided. It simplifies the procedure and leads to satisfactory cosmetic results.

Serum profile of pro- and anti-inflammatory cytokines in rats following implantation of low-temperature plasma-modified titanium plates.

Surface modification of Titanium (Ti) by low-temperature plasma influences cell-material interactions. Therefore, this study aimed at examining serum cytokine levels and associations after intramuscular implantation (n = 8 rats/group) of Ti-plates with Plasma Polymerized Allyl Amine (Ti-PPAAm), Plasma Polymerized Acrylic Acid (Ti-PPAAc), and without such layers (Ti-Controls). Pro-inflammatory (IL-2, IFNγ, IL-6) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were measured weekly for 56 days. Ti-PPAAm caused increased IL-2 (d7-14, d35), increased IFNγ (d35) and decreased IL-10 (d35, d49-56). Ti-PPAAc induced divergent anti-inflammatory cytokine changes with increased IL-4 (d28-56) and decreased IL-10 (d42-56). Ti-Controls elicited increased IL-2 (d42) and IFNγ (d35-42, d56). IL-6 was not detected and IL-13 only in three samples, thus they do not influence the response against these Ti implants. Correlation analysis revealed surface-dependent associations between cytokines indicating the involvement of different inflammatory cell populations. Concluding, different plasma modifications induce specific serum cytokine profiles and associations indicating distinct inflammatory responses.

Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs.

Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

Morphometric immunohistochemical examination of the inflammatory tissue reaction after implantation of calcium phosphate-coated titanium plates in rats.

Calcium phosphate (CaP) preparations are established coatings for titanium-based medical implants used for bone reconstruction. However, biodegradation of the coating can result in microparticles that subsequently cause inflammatory reactions. The present study was therefore aimed at investigating the inflammatory response to two series of CaP-coated titanium plates: Ti-brushite (Ti-B) and Ti-hydroxyapatite (Ti-H) implants. Fifteen male LEW.1A rats received one plate of each series and a pellet (5 x 2 mm) of sol-gel derived silica/CaP (SCP implants) implanted into the back musculature. After 7, 14 and 28 days, five rats were killed and the implants were removed with the surrounding tissue. Quantitative immunohistochemistry was performed on frozen sections. Total monocytes/macrophages, tissue macrophages, T-cells, MHC-class-II-positive cells and proliferating cells were counted. For the Ti-B implants, the number of monocytes/macrophages remained constant while the other cell populations increased. In contrast, for the Ti-H implants the number of monocytes/macrophages decreased while the other cell populations remained constant. The SCP implants demonstrated degradation and scattering into smaller particles with an increase for all cell populations except the proliferating cells. Human mesenchymal stem cells demonstrated adherence and a flat morphology on Ti-B and Ti-H implants and no remarkable difference between both implants. Taken together, the in vivo data demonstrate that the short-term inflammatory response against a hydroxyapatite coating is lower in comparison to a brushite coating, and that the morphology of cells growing in vitro is similar on both layers.

Local tissue reaction and differentiation of the prosthesis-specific antibody response following functional implantation of vascular grafts in pigs.

The study was aimed at investigating the local tissue reactions through a histological examination of beta-1-integrin expression and neointima formation, and humoral immune responses by detection of prosthesis-specific antibodies, after functional implantation of vascular prostheses. In three groups of pigs, the infrarenal aorta was replaced with segments of collagen-impregnated Dacron-prostheses: M-prosthesis--medium primary porosity, double velour layer, crimping; C-prosthesis--low primary porosity, no velour, crimping; T-prosthesis--high primary porosity, no velour, no crimping. For each prosthesis type, one series with four animals was used for examining the tissue reactions, and a second series with eight animals was used to study the antibody response, both until 116 days postoperative. In the first three weeks, the M-prosthesis caused the highest tissue reactions and the highest antipolyester antibodies, but the lowest anticollagen antibodies, whereas the T-prosthesis caused the highest anticollagen antibodies, but the least tissue response and antipolyester antibodies in the early phase. On day 116, the C-prosthesis caused the highest tissue reactions and highest polyester-specific antibodies. These results indicate a possible association between local inflammatory reactions and humoral immune responses, influenced by properties of vascular grafts.

Evaluation of the biocompatibility of a new vascular prosthesis coating by detection of prosthesis-specific antibodies.

In recent experimental studies, we could demonstrate the occurrence of antibodies against the prosthesis matrix and coating following implantation of polyester-based vascular grafts. Therefore, this study aimed at evaluating the biocompatibility of a new absorbable polymer coating by detection of antibodies against the coating and the polyester matrix. Two polyester vascular prostheses coated either with the polymer (PP-prosthesis) or with gelatine (PG-prosthesis) were functionally implanted into sheep (n = 22 per group). Blood was drawn on days 1 (pre-OP) and 7, 14, 28, 56, 84, 140 (post-OP). Homogenates from both prostheses (PP-target or PG-target) or from an uncoated prosthesis (P-target) were used as assay targets in a particle-based immunoassay. The antibody binding against the P-target was significantly higher in the PP-group than in the PG-group on days 7-56, but not on days 84 and 140. Within both groups, no significant differences but a significant correlation between the binding against the P-target and the coated target was found. Therefore, the absorbable polymer did not induce a specific humoral immune response. In conclusion, the overall immunogenicity of the polymer-coated graft was comparable to the gelatine-coated graft. The detection of prosthesis-specific antibodies seems to be useful for in vivo biocompatibility testing.

Immune response against polyester implants is influenced by the coating substances.

The aim of this study was to evaluate the influence of the coating of polymer implants upon the individual humoral immune response to the polymer matrix. Intramuscular implantation and explantation of samples from three different polyester vascular prostheses coated with collagen, gelatin, or human serum albumin was performed in LEW.1A rats and subsequently compared to sham operated control animals. Antibodies in serum samples were detected by means of enzyme immunoassays employing particles of pure polyester and the respective prosthesis, or solid phase bound coating substances as targets. In contrast to the controls, all animals with implants demonstrated a high antipolyester antibody response with a broad individual variability graduated according to the prosthesis coatings: gelatin > albumin > collagen. This was further significantly increased after the second implantation/first explantation and declined following the last explantation. Only animals with albumin-coated implants revealed specific antibodies to the coating as well as the strongest overall immunological reaction against the prosthesis already on day 8. Specificity of polymer antibodies was demonstrated by competitive inhibition of median antibody binding. Our results showed a specific immune reaction as a result of the applied polymer, which varied due to the surface-coating and individual factors.

Digital image analysis for morphometric evaluation of tissue response after implanting alloplastic vascular prostheses.

The aim of this study was to examine the suitability of digital image analysis, using the KS400 software system, for the morphometric evaluation of the tissue response after prosthesis implantation in an animal model. Twenty-four female pigs aged 10 weeks were implanted with infrarenal Dacron(R) prostheses for 14, 21, 28, and 116 days. Following the explantation and investigation of the neointima region, the expression of beta-1-integrin, the proliferation rate by means of Ki-67 positive cells, and the intima thickness were evaluated as exemplary parameters of the tissue response after implantation. Frozen tissue sections were immunohistochemically stained and subsequently examined using computer-aided image analysis. A maximum expression of 32.9% was observed for beta-1-integrin 14 days after implantation, gradually declining over time to 9.8% after 116 days. The proliferation rate was found to be 19% on day 14, increasing to 39% on day 21 with a subsequent gradual decline to 5% after 116 days. The intima thickness increased from 189.9 microm on day 14 to 1228.0 microm on day 116. In conclusion, digital image analysis was found to be an efficient and reproducible method for the morphometric evaluation of a peri-prosthetic tissue response.

Preoperative application of selective angiographic embolization in the treatment of focal nodular hyperplasia.

A focal nodular hyperplasia (FNH) rarely requires surgical intervention unless complications or clinical symptoms come into play. In 2 female patients, ages 35 and 44, with symptomatic tumors of that entity (10 and 14 cm, respectively, in size) we performed a laparoscopic liver resection. Directly before undergoing this operation they underwent a selective angiographic embolization of the arterial inflow for control of hemorrhage by application of polyvinyl alcohol particles to the afferent arteries. This procedure led to a complete interruption in arterial inflow and the subsequent laparoscopic resection itself could be carried out as planned with minimal blood loss as well an uncomplicated postoperative course. The patients demonstrated a high degree of subjective satisfaction with the procedure. A reduction in arterial inflow through selective embolization is a useful tool in the preparation for laparoscopic resection of large, well-vascularized liver tumors.

Pathophysiological measurement and results after laparoscopic fundoplication for gastroesophageal reflux disease.

PURPOSE: Both surgical and conservative treatments for gastroesophageal reflux disorder (GERD) are controversial. The aim of this prosepective study was to examine outcomes after laparoscopic antireflux surgery. METHODS: The subjects were 143 patients who underwent laparoscopic antireflux surgery. Following diagnostic procedures 126 patients were allocated to a total fundoplication group (360 degrees C, Nissen-DeMeester) and 17, to a posterior semifundoplication group (250-270 degrees, Toupet). All complications were registered, and pathophysiological and outcome data were examined 3, 6, and 9 months after surgery. RESULTS: By 6 months after surgery the mean lower esophageal sphincter (LES) pressure had improved significantly, to 14.8 mmHg in the Nissen-DeMeester group, and to 12.1 mmHg in the Toupet group, corresponding to successful prevention of esophageal reflux in both groups. Dysphagia was more common in the early postoperative period after total fundic wrap (17% vs12%), but this difference disappeared in time. All patients reported complete relief of reflux symptoms, although two of those who underwent the Nissen-DeMeester fundoplication experienced relapse of GERD and required open reconstruction (1.4%). The laparoscopic procedure was converted to open surgery in three patients (2%). There were no associated deaths and the perioperative complication rate was 4.2%. CONCLUSION: Laparoscopic antireflux surgery is an effective treatment for GERD. More than 93% of the patients in this series rated their outcome as good to excellent following the operation.