Comparison of adhesion prevention capabilities of the modified starch powder-based medical devices 4DryField® PH, HaemoCer™ PLUS and StarSil® in the Optimized Peritoneal Adhesion Model.

Background and Objectives: The rat Optimized Peritoneal Adhesion Model (OPAM) was developed to provoke adhesion formation with high reproducibility in incidence and extent. In a recent study, the starch-based hemostats 4DryField PH and Arista AH were tested for their capabilities to prevent adhesion formation, the former one certified for adhesion prevention and hemostasis, the latter one only certified for hemostasis. As two further starch-based hemostats, i.e., HaemoCer PLUS and StarSil, have officially been certified for adhesion prevention in the meantime, the present study was conducted to examine their efficacy. Materials and Methods: For this purpose, all three products were applied as a powder that was mixed in situ with saline solution to form a barrier gel. Adhesions were scored using the established macroscopically scoring systems by Lauder and Hoffmann, as well as histopathologically using the score by Zühlke. Animals receiving saline solution solely served as controls. Results: As previously published, 4DryField PH reduced peritoneal adhesions significantly. In contrast, HaemoCer PLUS and StarSil did not lead to a statistically significant reduction of adhesion formation. When comparing 4DryField PH, HaemoCer PLUS and StarSil, 4DryField PH was significantly more effective in preventing peritoneal adhesions. The results of the macroscopic investigation were confirmed by histopathological evaluations. Conclusions: Only 4DryField PH but neither HaemoCer PLUS nor StarSil were capable to effectively prevent adhesion formation, corroborating the assumption that starch-based hemostats do not generally have the capability to act as effective adhesion prevention devices.

Comparison of adhesion prevention capabilities of the modified starch powder-based medical devices 4DryField® PH and Arista™ AH in the Optimized Peritoneal Adhesion Model.

Adhesion barriers can be based on numerous substances. In the rat Optimized Peritoneal Adhesion Model (OPAM) the starch-based hemostats 4DryField and Arista were tested for their capability to act in a preventive manner against adhesion formation (applied as a powder that was mixed in situ with saline solution to form a barrier gel). Adhesions were scored using the established scoring systems by Lauder and Hoffmann, as well as histopathologically using the score by Zühlke. Animals receiving saline solution were used as controls. As previously published, 4DryField reduced peritoneal adhesions significantly. However, Arista did not lead to a statistically significant reduction of adhesion formation. When comparing 4DryField and Arista applied in the same manner, only 4DryField was significantly effective in preventing peritoneal adhesions. Histopathological evaluations confirmed the results of the macroscopic investigation, leading to the conclusion that starch-based hemostats do not generally have the capability to function as effective adhesion prevention devices.

Decreased superficial surgical site infections, shortened hospital stay, and improved quality of life due to incisional negative pressure wound therapy after reversal of double loop ileostomy.

This single-center prospective, controlled observational study investigates the impact of incisional negative pressure wound therapy on wound healing processes and its potency to prevent superficial surgical site infections (SSSI) after reversal of a double loop ileostomy. Furthermore, this study gains insight in socioeconomic aspects, like duration of hospital stay and, for the first time, patient's quality of life during the incisional negative pressure wound treatment. To address this question, an interventional group of 24 patients treated with incisional negative pressure wound therapy (Prevena incisional wound management system, KCI, Germany) and a respective control cohort of 25 patients treated with a standard sterile dressing were observed for 30 days in the postoperative course. Postoperative incisional negative pressure wound therapy resulted in statistically significant decreasing duration of hospital stay (6 days vs. 9 days, p = 0.019) and lower rates of SSSIs (12.5% vs. 20.0%, p = 0.478) in accordance with a not statistically significant decreased necessity of postoperative antibiotic therapy (12.5% vs. 36%, p = 0.051). To survey subjective items of well-being and quality of life, all patients were asked to answer a questionnaire. Patients of both groups noticed increasing quality of life after reversal of their ileostomy. However, patients treated with an incisional negative pressure wound therapy had a superior improvement of a variety of subjective items, resulting in an overall much better satisfaction with the course of wound healing. Our findings suggest, that incisional negative pressure wound therapy seems to be a reasonable therapeutic option to reduce incidence of SSSIs and to have a beneficial impact to patient's quality of life, as well as, socio-economic aspects.

Adhesion Prevention Efficacy of Composite Meshes Parietex®, Proceed® and 4DryField® PH Covered Polypropylene Meshes in an IPOM Rat Model.

Background: Adhesions to intraperitoneally implanted meshes (IPOM) are a common problem following hernia surgery and may cause severe complications. Recently, we showed that missing peritoneal coverage of the intestine is a decisive factor for adhesion formation and 4DryField® PH (4DF) gel significantly prevents intestine-to-mesh adhesions even with use of uncoated Ultrapro® polypropylene mesh (UPM). The present study investigates adhesion prevention capability of coated Parietex® mesh (PTM) and Proceed® mesh (PCM) in comparison to 4DF treated UPM. Methods: 20 rats were randomized into two groups. A 1.5 x 2 cm patch of PTM or PCM was attached to the abdominal wall and the cecum was depleted from peritoneum by abrasion. After seven days incidence of intestine-to-mesh adhesions was evaluated using Lauder and Hoffmann adhesion scores. Histological specimens were evaluated; statistics were performed using student's t-test. The data were compared with recently published data of 4DF treated uncoated UPM. Results: Use of PTM or PCM did not significantly diminish development of intestine-to-mesh adhesions (adhesion reduction rate PTM: 29%, p = 0.069 and PCM: 25%, p = 0.078). Histological results confirmed macroscopic finding of agglutination of intestine and abdominal wall with the mesh in between. Compared to these data, the use of UPM combined with 4DF gel reveals significantly better adhesion prevention capability (p < 0.0001) as shown in earlier studies. However, in clinical situation interindividual differences in adhesion induction mechanisms cannot be excluded by this experimental approach as healing responses towards the different materials might vary. Conclusion: This study shows that in case of impaired intestinal peritoneum coated PTM and PCM do not provide significant adhesion prevention. In contrast, use of UPM combined with 4DF gel achieved a significant reduction of adhesions. Hence, in case of injury of the visceral peritoneum, application of a polysaccharide barrier device such as 4DF gel might be considered more effective in reducing intestine-to-mesh adhesions than coated mesh devices.

Treatment of de-peritonealized intestine with 4DryField® PH prevents adhesions between non-resorbable intra-peritoneal hernia mesh and bowel.

BACKGROUND: Intraperitoneal onlay meshes (IPOM) can be associated with intestine-to-mesh adhesion formation, implementing risks like pain, enterocutaneous fistula, infection, and female infertility. This study investigates, whether a treatment of impaired intestinum with the anti-adhesive and hemostyptic agent 4DryField® PH prevents adhesion formation. METHODS: In 20 male LEWIS rats uncoated polypropylene meshes were sewn to the inner abdominal wall and the cecum of the respective animal was de-peritonealized by peritoneal abrasion by a gauze swap, and meso-sutures ensured a constant contact of injured areas. Rats were treated with 4DryField® PH gel either premixed or applied as a powder with in-situ transformation (100 mg powder plus 0.4 ml 0.9% saline solution). One week postoperatively, the extent of intestine-to-mesh adhesions and the quality of mesh ingrowth were evaluated macroscopically by two independent investigators using two scoring systems. Furthermore, specimens were analysed microscopically. All data were compared with control animals without 4DryField® PH treatment and analysed statistically using student's t-test. RESULTS: Treatment of de-peritonealised cecum with 4DryField® PH significantly reduced intestine-to-mesh adhesions in both treatment groups as compared to controls without 4DryField® PH treatment (68% reduction with premixed gel, P<0.0001; 80% reduction with in-situ gel, P<0.0001). There was no impact on the quality of mesh ingrowth, confirmed histologically by a single-layer mesothelial coverage. CONCLUSION: These experiments mimick clinical IPOM implantation scenarios with adjacent bowel depleted from peritoneum. 4DryField® PH gel treatment resulted in intestinal mesothelial surface recovering without development of bowel-to-mesh adhesions. Concurrently, integration of mesh into the abdominal wall is undisturbed by 4DryField® PH treatment.

Evaluation of 4DryField® PH as Adhesion Prevention Barrier Tested in an Optimized Adhesion Model in Rats.

BACKGROUND: Adhesions due to pelvic/abdominal surgery are a common serious pathology possibly entailing severe complications. This study investigates the adhesion prevention capability of the novel starch-based agent 4DryField® PH, which together with saline solution forms a barrier gel. Herein, an optimized adhesion model (OPAM) inducing severe adhesions/agglutinations with high reproducibility was used. METHODS: In 19 Lewis rats, a 1 × 2 cm abdominal wall defect was created, the peritoneum of the neighboring cecum was abraded, and both injured areas were approximated by suture. Rats were randomized to control (n = 10) or 4DryField PH treatment (n = 9) groups. Another 8 rats had sham surgery for safety assessment of 4DryField PH. At day 7, the quantity and quality of adhesions were assessed macro-/microscopically and evaluated statistically. RESULTS: 4DryField PH treatment significantly reduced the incidence and severity of adhesions as verified by significantly improved adhesion scorings (0.4 vs. 4.5; 1.1 vs. 9). Histology revealed reconstitution of the cecum and abdominal wall including regeneration of the visceral/parietal peritoneum. In sham-operated rats, 4DryField PH did not induce adhesion formation. CONCLUSIONS: 4DryField PH gel was highly effective in preventing adhesions. Histologically, the injured cecum and abdominal wall regenerated well in the presence of 4DryField PH. Considering the severity of OPAM trauma, the potential of 4DryField PH to prevent adhesions can be rated excellent.

Evaluation of the biological tolerability of the starch-based medical device 4DryField® PH in vitro and in vivo a rat model.

PURPOSE: To evaluate in vitro cytotoxicity/biocompatibility as well as in vivo tolerability of the novel polysaccharide 4DryField® PH, certified for haemostasis and adhesion prevention. METHODS: In vitro cytotoxicity/viability testing according to ISO EN 10,993 using murine and human tumour cell lines incubated with 4DryField® PH (PlantTec Medical GmbH). Using a rat model the impact of 4DryField® PH on animals viability and in vivo effects were macro- and micropathologically assessed. RESULTS: In vitro testing revealed no cytotoxic effect of 4DryField® PH nor enhancement of viability to tumour cell lines. In vivo viability of rats was unimpaired by 4DryField® PH. Bodyweight loss in animals with abdominal injury plus treatment with 4DryField® PH was in the range of controls and less than in injured rats without treatment. At day 7 after surgery no formation of adhesions, neither macroscopic nor histological remnants nor signs of foreign body reaction were present in animals without injury. In animals with peritoneal injury and 4DryField® PH application, histopathological observation revealed minor residuals of polysaccharide in the depth of wound cavity embedded in a thickened subperitoneal layer; however, with a suggested intact neoperitoneum. The presence of mononuclear cells surrounding polysaccharide particles in varying states of degradation was observable as well. CONCLUSION: 4DryField® PH is not cytotoxic and does not enhance viability of tumour cell lines. High dose of 4DryField® PH of 1.09 g/kg bodyweight is well tolerated and reduces weight loss in animals with peritoneal injury. The biocompatibility of 4DryField® PH can be rated as being excellent.

High reproducibility of adhesion formation in rat with meso-stitch approximation of injured cecum and abdominal wall.

OBJECTIVE: Peritoneal adhesions following surgery are a common, serious pathology with severe complications. Appropriate animal adhesion models are essential for the assessment of adhesion preventing medical devices. This study introduces a variation of an established rat model in which highest degree adhesions are induced with excellent reproducibility (OPAM=optimized peritoneal adhesion model). Thus, this model seems to be eligible to study effects of adhesion preventing devices. METHODS: 24 Lewis male rats were divided into four groups (OPAM, WSFX, sham-OPAM, sham-WSFX). The OPAM technique comprised cecal abrasion, creation of an abdominal wall defect plus approximation of injured areas by a suture, which was compared to a setting of lesions without suture fixation (WSFX). All rats were sacrificed at day 7. Macroscopic and histopathological evaluations were performed. RESULTS were statistically analyzed using ANOVA and Dunnett's test. RESULTS: In OPAM rats macroscopic analyses revealed a 90% incidence adhesion of cecum to the abdominal wall, all adhesions imposing as complete agglutination. In WSFX animals incidence of adhesions formation was 75%, while in both sham groups there were no adhesions at all. Histology showed the structure of adhesions with merged smooth muscle of colon and skeletal muscle of abdominal wall in all cases. CONCLUSION: OPAM technique provides adhesions of injured areas with a better probability than with conventional methods. All OPAM adhesions impressed as highest degree adhesions, i.e. agglutination. Due to high reproducibility in incidence and extend of adhesion formation, the OPAM is recommended for testing of adhesion prevention medical devices.

Induction of chronic renal allograft dysfunction in a rat model with complete and exclusive MHC incompatibility.

Chronic allograft dysfunction is one of the most important reasons for late graft loss after renal transplantation. Its etiology is multifactorial and combines immunological as well as non-immunological mechanisms. It is known from large registry data that MHC mismatches are inversely correlated to long term allograft survival. Although this is a well known aspect, the mechanisms of MHC-driven graft damage and the impact of other immunological factors leading to chronic rejection are poorly understood. In patients it is impossible to study MHC mismatches without considering non-MHC differences. Further more common animal models for chronic rejection are all characterized by non-MHC as well as MHC disparities. To exclusively study MHC mediated immunoresponses we established a rat model of renal transplantation using congenic rat strains differing in their entire MHC class I and class II, but sharing the genetic background of the LEW rat. After an initial short term of immunosuppression all animals developed renal impairment with severe albuminuria. Half of the animals died of renal failure in week 7 to 14 and showed pathological characteristics of chronic allograft damage including IF/TA and severe glomerulopathy. The majority of these recipients developed circulating donor-specific MHC alloantibodies. Allografts were significantly infiltrated with T-cells, macrophages and NK-cells. We established a MHC congenic rat model to investigate immunological mechanisms of chronic renal allograft rejection exclusively induced by a complete MHC mismatch. We demonstrated humoral as well as cellular immunoresponses leading to chronic allograft loss in 50% of animals.