OBJECTIVE: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide.
OBJECTIVE: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery.
METHODS: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included.
RESULTS: We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0-67%, and 85%, respectively.
CONCLUSIONS: Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.

Introduction Post-operative adhesions present a number of difficulties, including intestinal obstruction and infertility, and they frequently require readmission due to adhesion-related problems. Notwithstanding these ramifications, there are surprisingly few thorough national surveys that address surgeons\' awareness of adhesives. By assessing Saudi surgeons\' knowledge of post-operative adhesions and their use of anti-adhesive medications, this study aims to close this knowledge gap. Methods This study is a cross-sectional observational research study aimed at Saudi Arabian surgeons utilizing a self-administered, semi-structured online questionnaire. The questionnaire was distributed to participants via social media and in-person email using basic random selection. It included adhesion morbidity and prevalence, pre-operative informed consent issues, adhesion preventive viewpoints, and anti-adhesive chemical use. Results There were 111 participants in total, of 41% were experienced surgeons with more than five years of experience. According to the survey, the majority of surgeons occasionally employed anti-adhesive compounds, especially during laparotomies (28%), and 38% never used them during laparoscopies. The study found that participants varied in what they informed patients regarding adhesion complications: 25% of participants informed 5%-10% of the patients about the possible adhesion complications in laparotomy procedures, whereas 26% of participants informed 10-25% of the patients in laparoscopic procedures. Compared with their specialist peers, general surgeons agreed more on the clinical significance of adhesions and prevention. Notably, three-quarters of participants were unclear about when to use anti-adhesive compounds. Conclusion While acknowledging the clinical significance of post-operative adhesions and recognizing the potential for prevention, most surveyed surgeons did not include adhesions as a post-operative complication in informed consent. The study underscores a belief in the efficacy of anti-adhesives yet reveals a widespread lack of clarity regarding specific indications for their use. Recommendations include implementing educational sessions during surgical training to heighten awareness of adhesions as a major post-operative complication and to encourage the appropriate utilization of available barriers and pharmacological anti-adhesive products.

Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti-inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in-vitro model systems as well as in-depth study of in-vivo models to evaluate the efficiency of anti-adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell-based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti-adhesion agents represent a promising approach for reducing the burden of adhesion-related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.

Postoperative adhesion remains a problem in surgery and causes postoperative complications. Laparoscopic surgery is now common, making it increasingly important to develop injectable formulations of adhesion barriers that can be applied during such surgeries. Temperature-responsive injectable polymer (IP) systems exhibiting a sol-to-gel transition in response to temperature are promising candidates as effective adhesion barriers that can be applied conveniently during laparoscopic surgery. We previously developed IP systems exhibiting temperature-responsive irreversible gelation based on a triblock copolymer of poly(ε-caprolactone-co-glycolic acid) (PCGA) and poly(ethylene glycol) (PEG) (PCGA-b-PEG-b-PCGA: tri-PCG) and a tri-PCG derivative with acrylate groups at the termini (tri-PCG-acryl). A mixture of tri-PCG-acryl micelle solution and tri-PCG micelle solution containing polythiol exhibited an irreversible sol-to-gel transition in response to a temperature increase. The gel contains partial covalent cross-linking, and the degradation and physical properties of these IP hydrogels can easily be controlled by changing the mixing ratio of tri-PCG-acryl in the formulation. In this study, we investigated the effect of physical properties of the IP hydrogel on the efficacy of adhesion prevention using our IP system containing various amounts of tri-PCG-acryl. Our results show that an IP system with lower physical strength and rapid degradation reduces adhesion more effectively. Chymase plays a crucial role in exacerbating adhesion formation, and a peptide derivative-type chymase inhibitor (CI), Suc-Val-Pro-PheP(OPh)2, was previously reported to prevent adhesion. We thus investigated the concomitant use of this CI with our IP system using two methods: separate administration of the CI and IP and entrapping the CI in the IP hydrogel. IP systems with separately administrated CI provided better results than the administration of an IP system entrapping the CI or sole IP systems. These findings suggest that the pharmacological effect of the CI and a physical barrier generated by our IP system effectively prevents adhesion.

Partial liver resection is an established treatment for hepatic disorders. However, surgical bleeding, intra-abdominal adhesion and rapid liver regeneration are still major challenges after partial liver resection, associated with morbidity and mortality. Herein, a biomimetic hybrid hydrogel, composed of oxidized hyaluronic acid, glycol chitosan and MenSCs-derived conditioned medium (CM), is presented to address these issues. The hybrid hydrogel is formed through reversible Schiff base, and possesses injectability and self-healing capability. Moreover, hybrid hydrogel exhibits the capabilities of hemostasis, anti-infection, tissue adhesion and controllable release of cargoes. Based on in vivo studies of the multifunctional hybrid hydrogel, it is demonstrated that acute bleeding in partial liver resection can be ceased immediately by virtue of the hemostasis features of hybrid hydrogel. Also, a significant reduction of intra-abdominal adhesion is confirmed in hybrid hydrogel-treated resection surface. Furthermore, upon the treatment of hybrid hydrogel, hepatic cell proliferation and tissue regeneration can be significantly improved due to the controllably released cytokines from MenSCs-derived CM, exerting the effects of mitogenesis and anti-inflammation in vivo. Thus, the biomimetic hybrid hydrogel can be a promising candidate with great potential for application in partial liver resection.

Investigations about ventral hernia repair are focused on improving the quality, resistance, and biocompatibility of mesh. This study compared plain polypropylene mesh with a pectin-honey hydrogel-coated polypropylene mesh in an acute hernia model in rats. Forty Wistar rats, randomly assigned to two groups, were submitted to laparotomy, and a 1 cm × 2 cm fascial defect was created, centered on the midline. Uncoated (group C) or coated mesh (group T) was inserted in an inlay fashion to repair the defect. After 30 days, the rats were euthanized, and the presence of adhesions to the mesh was macroscopically evaluated. Histology and measurement of COX-2 as tissue inflammation markers were used to assess fascia tissue healing. Grades of adhesion were not different between groups. Histological score and COX-2 expression were not significantly different between groups, except for the higher inflammatory response demonstrated in group T. The pectin-hydrogel coated mesh could not reduce adhesion formation compared to uncoated polypropylene mesh but improved peritoneal regeneration and tissue healing.

Dura mater defect and subsequent cerebrospinal fluid (CSF) leakage usually appear in trauma or neurosurgical procedures and are followed by a series of serious complications and even death. The use of a qualified dura mater substitute with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is one of the promising treatment methods. However, even though some products have been used in the clinic, none of the substitutes achieved the required multifunction. In this study, we aimed to design and fabricate a dura repair composite with the ideal multifunction. By biomimicking the structure and component of natural dura, we applied poly(L-lactic acid) (PLLA), chitosan (CS), gelatin, and acellular small intestinal submucosa (SIS) powders to successfully prepare a triple-layered composite. Then, a series of specific devices and techniques were developed to investigate the performance. The results revealed that satisfactory structural stability could be realized under good synergistic interactions among the components. In addition, all the findings suggested that the bionic triple-layered composite showed satisfactory multifunction of leakage blockade, adhesion prevention, antibacterial property, and dura reconstruction potential, and thus, it might be a promising candidate for dura repair. STATEMENT OF SIGNIFICANCE: Developing qualified dura mater substitutes with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is crucial for treating dura mater defect and subsequent cerebrospinal fluid (CSF) leakage that appear in trauma or neurosurgical procedures. In this study, we designed and fabricated a triple-layered dura repair biocomposite with satisfactory structural stability and desired multifunction based on biomimicking of the structure and component of natural dura. Moreover, a series of specific devices and techniques were developed to investigate the relevant performance. Overall, the developed hydrogel electrospinning system exhibited excellent advantages in achieving multifunction and could be applied widely in the future to achieve multifunctional tissue repair materials.

Tissue adhesion is a severe postoperative complication. Various strategies have been developed to minimize postoperative adhesion, but the clinical efficacy is still far from satisfactory. Herein, we present a dual dynamically crosslinked hydrogel to serve as a physical postoperative anti-adhesion barrier. The hydrogel was generated by dynamic chemical oxime bonding from alkoxyamine-terminated Pluronic F127 (AOP127) and oxidized hyaluronic acid (OHA), as well as hydrophobic association of AOP127. Rheological analysis demonstrated that the hydrogel exhibits temperature sensitivity. At 37 °C, it shows much higher modulus and higher stability than the Pluronic F127 hydrogel. Hemolytic assays suggested that the hydrogel undergoes low hemolysis. In addition, it exhibited anti-adhesion to blood cells in blood cell adhesion tests. It also showed an anti-attachment effect to fibroblasts and biocompatibility in vitro cell studies. Macroscopic evaluation and lap-shear tests revealed that the hydrogel has a moderate adhesive capacity to tissue, which is important for self-fixation. A rat model of sidewall defect-bowel abrasion was established to evaluate the anti-adhesion effect in vivo. The gross observation and pathological analysis revealed a significant reduction in postoperative peritoneal adhesion in the AOP127/OHA hydrogel-treated group than those treated with normal saline or Pluronic F127 hydrogel. Hence, the dual dynamically crosslinked hydrogel with self-fixable capacity may be suitable as a physical barrier for postoperative adhesion prevention. STATEMENT OF SIGNIFICANCE: Despite the development of numerous postoperative anti-adhesion barriers, their anti-adhesion efficacy is still limited in clinical trials due to poor tissue adhesion and rapid clearance from injured areas. Herein, we have developed a dual dynamic crosslinked hydrogel, generated by dynamic oxime bonds and hydrophobic interactions. The hydrogel is temperature-sensitive and demonstrates moderate tissue adhesion capacity, which allows for self-fixation when applied to defects. The introduction of dynamic covalent bonds improves the stability of the hydrogel. Moreover, the hydrogel not only displays appropriate hemocompatibility, cytocompatibility and anti-adhesion of blood cells and fibroblasts, but it also effectively contributes to preventing postoperative peritoneal adhesions in vivo. Hence, this dual dynamic crosslinked hydrogel may have potential applications as a physical barrier in clinical practice.

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.

Introduction: Intra-uterine adhesion (IUA) is one of the main causes of secondary infertility. The aim of this study was to evaluate the prevalence of IUA developing in women undergoing hysteroscopic resection for submucous myomas, polyps, and intrauterine synechiae and test the efficacy of second look hysteroscopy for diagnosing and treating post-surgical adhesions. Materials and Methods: We retrospectively collected data from reproductive age women who had a second look office hysteroscopy following hysteroscopic resection for myoma, polyp, or IUA at Foch hospital (Suresnes, France) between 2009 and 2017. Results: Six hundred and twenty two reproductive-age women underwent hysteroscopic resection for myoma, polyp, and/or IUA. Among them, 155 women had a second look hysteroscopy. In this group, 29/155 (18.7%) had IUA formation: 17/83 (20.5%) women who underwent hysteroscopic myomectomy, 5/46 (10.9%) women who underwent hysteroscopic polypectomy, and 7/26 (26.9%) women who underwent hysteroscopic lysis of adhesions. These IUA have been lysed by the office hysteroscopy procedure in 16/29 (55.2%) patients: 11/17 (64.7%), 2/5 (40%), and 3/7 (42.9%) in women who underwent hysteroscopic myomectomy, polypectomy and lysis of adhesion, respectively. Conclusion: IUA is a common complication of hysteroscopic surgery. Second look office hysteroscopy is an easy and effective procedure for diagnosing and removing newly formed IUA. It should be recommended for all women undergoing hysteroscopic resection for myomas, polyps, or IUA.