Expression of CD68 positive macrophages in the use of different barrier materials to prevent peritoneal adhesions-an animal study.

In preventing postoperative adhesion formation the optimal barrier material has still not been found. It is therefore imperative to assess the biocompatibility of potential barrier devices. Macrophages play a decisive role in the regulation of wound healing, tissue regeneration and foreign body reaction. Since the number of CD68-positive macrophages represents an important parameter within biomaterial testing, in the present study it was analysed whether a correlation exists between the total number of CD68-positive macrophages and the extent of fibrosis or inflammation in peritoneal adhesion prevention using biomaterials. After standardized peritoneal wounding, Wistar rats were treated with five adhesion barriers or remained untreated as a control. After 14 days, animals were sacrificed and the treated areas were evaluated histomorphologically and immunohistologically. A heterogeneous pattern of macrophage count in relation to fibrosis or inflammation was found. While some groups described a moderate macrophage infiltration without fibrosis, others showed similar numbers of macrophages, but accompanied by moderate fibrosis. Moreover, a minimal number of macrophages was associated with minimal fibrosis. Mild inflammation was seen both with minimal and moderate macrophage infiltration. Altogether, no correlation could be established between the tissue response and the count of CD68-positive macrophages. With a view to macrophage heterogeneity further studies are required to determine the different macrophage subpopulations and clarify the role of these in the tissue responses to barrier materials.

A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model.

PURPOSE: To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model. METHODS: In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded. RESULTS: Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001). CONCLUSIONS: This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time.

Mesothelial morphology and organisation after peritoneal treatment with solid and liquid adhesion barriers--a scanning electron microscopical study.

Separation of traumatized tissue represents the only promising strategy in postoperative adhesion prevention, a relevant clinical problem after surgical intervention. In the present study scanning electron microscopy (SEM) and subsequent morphometry were used to analyse the tissue response to five commercial adhesion barriers. Standardised peritoneal lesions in Wistar rats were covered with solid and viscous barrier materials and semiquantitatively analysed 14 days postoperatively. Striking morphological differences in lesion surface organisation between the barrier groups became apparent with colonisation of the barrier by mesothelial cells to different degrees. Furthermore, the mesothelial cells showed either a normal or activated phenotype depending on the underlying biomaterial. These experiments demonstrate that the examination by SEM gives useful insights into the performance of barrier materials and the cellular processes of adhesion prevention, since mesothelial cells play an active role in the pathogenesis of adhesion formation.

A direct comparison of seprafilm, adept, intercoat, and spraygel for adhesion prophylaxis.

BACKGROUND: Commercially available agents for adhesion prophylaxis are legion but there is a lack of direct comparisons between them. Here we compare four of the most commonly used adhesion barriers against a control group in a clinically relevant rat model. MATERIAL AND METHODS: Standardized lesions were created in Wistar rats using electrocautery and suturing. Subsequently, the experimental lesions were treated with Seprafilm (n = 30), Adept (n = 30), Intercoat (n = 30), Spraygel (n = 30), or no barrier (n = 30). The resulting adhesions were examined 14 d postoperatively. RESULTS: The mean area covered by adhesion was 77% in the control group, 46% in animals treated with Seprafilm, 54% in animals treated with Adept, 55% in animals treated with Intercoat, and 68% in animals treated with Spraygel. The adhesion-free incidence was 20% (n = 6) of lesions treated with Seprafilm, 20% (n = 6) of lesions treated with Intercoat, 3% of lesions treated with Spraygel (n = 1), and 0% of lesions treated with Adept or the control group. CONCLUSIONS: There were statistically significant differences between the barriers with regards to the area covered by adhesions and the adhesion-free incidence. In spite of this, a significant adhesion burden remains with all of the tested barriers.

Tissue response to five commercially available peritoneal adhesion barriers-A systematic histological evaluation.

Separating wounded serosa by physical barriers is the only clinically approved adjunct for postoperative adhesion prevention. Since the optimal adhesion barrier has not been found, it is essential to improve our pathogenic understanding of adhesion formation and to compare the effects of different barrier materials on tissue and cells. Wistar rats underwent standardized peritoneal damage and were treated either with Seprafilm, Adept, Intercoat, Spraygel, SupraSeal or remained untreated as a control. 14 days postoperatively, the lesions were explanted and histomorphologically analyzed using the European ISO score to evaluate material implants. Striking differences between the material groups were present regarding the inflammation, fibrosis, and foreign body reaction. According to the ISO score, Intercoat and Spraygel were considered as nonirritating to tissue. Adept, Seprafilm, and SupraSeal were assessed as mild-irritating materials. Interestingly, the most effective material in adhesion prevention revealed moderate inflammation accompanied by minor fibrosis. The degree of inflammation to barrier materials does not predict the efficacy in the prevention of adhesions. Histopathological investigations are crucial to improve our understanding of the cellular mechanisms during adhesion formation and elucidate the tissue response to material approaches used in adhesion prevention. This will lead to improved antiadhesive strategies and the development of functional barrier biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 598-609, 2018.

Randomized experimental study to investigate the peritoneal adhesion formation of conventional monopolar contact coagulation versus noncontact argon plasma coagulation in a rat model.

OBJECTIVE: To investigate peritoneal adhesion formation of monopolar contact coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat model. DESIGN: Randomized, controlled, single-blinded animal study. SETTING: University laboratory. ANIMAL(S): Sixteen female Wistar rats. INTERVENTION(S): Bilateral lesions were created on the abdominal wall with MCC and APC in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. MAIN OUTCOME MEASURE(S): Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. RESULT(S): Average energy intake was 99.5 ± 7.39 J for APC and 95.7 ± 9.62 J for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for noncontact APC and 85.4% for MCC. MCC induced significantly more vascular adhesions. Histological evaluation revealed no significant differences regarding average depth of lesions induced by APC and MCC. Both groups showed almost identical morphology of necrosis and granulation tissue formation. CONCLUSION(S): This study compares for the first time adhesion formation of MCC versus noncontact APC in a rat model. With a similar energy intake, contact coagulation induced a significantly higher rate of adhesion formation. APC-induced adhesions were significantly less vascularized compared with MCC adhesions. Besides the thermal effects of both coagulation methods, the direct mechanical contact of the MCC electrode with the highly sensitive peritoneum is thus determined to be a pivotal additional stimulus for adhesion formation.

Current strategies and future perspectives for intraperitoneal adhesion prevention.

INTRODUCTION: The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION: Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review.

Intraperitoneal adhesions--an ongoing challenge between biomedical engineering and the life sciences.

Peritoneal adhesions remain a relevant clinical problem despite the currently available prophylactic barrier materials. So far, the physical separation of traumatized serosa areas using barriers represents the most important clinical strategy for adhesion prevention. However, the optimal material has not yet been found. Further optimization or pharmacological functionalization of these barriers could give an innovative input for peritoneal adhesion prevention. Therefore, a more complete understanding of pathogenesis is required. On the basis of the pathophysiology of adhesion formation the main barriers currently in clinical practice as well as new innovations are discussed in the present review. Physiologically, mesothelial cells play a decisive role in providing a frictionless gliding surface on the serosa. Adhesion formation results from a cascade of events and is regulated by a variety of cellular and humoral factors. The main clinically applied strategy for adhesion prevention is based on the use of liquid or solid adhesion barriers to separate physically any denuded tissue. Both animal and human trials have not yet been able to identify the optimal barrier to prevent adhesion formation in a sustainable way. Therefore, further developments are required for effective prevention of postoperative adhesion formation. To reach this goal the combination of structural modification and pharmacological functionalization of barrier materials should be addressed. Achieving this aim requires the interaction between basic research, materials science and clinical expertise.

A pilot study of laparoscopic adhesion prophylaxis after myomectomy with a copolymer designed for endoscopic application.

STUDY OBJECTIVE: To assess the laparoscopic handling and safety of D,L-polylactide-epsilon-caprolactone-trimethylene carbonate (PCT) copolymer after myomectomy and compare it with icodextrin. In contrast to previously developed solid barriers, the material has rationally designed properties that are advantageous for convenient laparoscopic application. DESIGN: A randomized, single-blinded clinical study (Canadian Task Force Classification I). SETTING: Single-center study in a German University Hospital. PATIENTS: Thirty patients who underwent laparoscopic myomectomy were enrolled. INTERVENTIONS: After laparoscopic myomectomy and subsequent reconstruction of the uterus with interrupted sutures, adhesion prophylaxis with either site-specific PCT copolymer or icodextrin occurred as per randomization. MEASUREMENTS AND MAIN RESULTS: Except in 1 case, complete coverage of the uterine wound was achieved with PCT copolymer, and the mean time taken for application was 6.7 minutes. Mean application time for icodextrin was 1.1 minute. After introduction into the abdomen, PCT copolymer changed into a flexible state that adapted very well to the operative anatomy. The patients were followed up according to the study protocol for 3 months. There were no unforeseen adverse events, possible adhesion-related complications, or nonspecific complications in either study arm. There was no significant difference in pelvic pain scores between PCT copolymer and icodextrin groups 3 months after surgery. CONCLUSION: In this pilot study, there were no adverse events, and the rationally designed material properties are favorable for laparoscopic application. No differences in postoperative pelvic pain were ascertained between PCT copolymer and icodextrin. Therefore a human phase II trial including second-look laparoscopy should be conducted to further evaluate this new solid adhesion barrier PCT copolymer.