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Morphology of adhesion peritoneum. H&E staining (left) and Masson staining (right) of representative human adhesion tissue.
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Postoperative adhesions (PA) are fibrotic tissues that are the most common driver of long-term morbidity after abdominal and pelvic surgery. The optimal drug or material to prevent adhesion formation has not yet been discovered. Comprehensive understanding of cellular and molecular mechanisms of adhesion process stimulates the design of future anti...
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... human adhesive tissues were markedly thickened, and filled with various cells by H&E staining, and Masson staining showed increased collagen deposition in the adhesive peritoneum (Figure 3). In addition to mesothelial and endothelial cells, and fibroblasts, a variety of inflammatory cells corresponding to neutrophils, macrophages, lymphocytes, mast cells were also present. ...
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Citations
... This spatial distribution is especially pertinent during abdominal surgeries, where neutrophils are stimulated to release NETs in reaction to tissue damage and the presence of foreign materials such as surgical sutures. The formation of NETs at these sites initiates a pro-inflammatory cascade that facilitates critical processes like fibrin deposition and fibroblast activation, which are essential for the development of peritoneal adhesions [147]. Furthermore, the process of histone citrullination, a modification associated with NET formation, serves as a precise biomarker for this phenomenon [5]. ...
Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molec-ular processes underlying their formation remain elusive. This review aims to assess the rela-tionship between neutrophil extracellular traps (NETs) and the generation of postoperative perito-neal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated us-ing the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a spe-cial focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal ad-hesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate post-operative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of per-itoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the rela-tionship between NETs and post-surgical adhesion formation to develop effective treatments.
... New anti-adhesion mechanisms and related anti-fibrotic drugs have also become a recent research hotspot [41]. Previously, the majority of anti-adhesion research had concentrated on transforming growth factor β1 and the suppression of extracellular regulatory protein kinases and their downstream effectors [42]. ...
Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.
... Until now, the means by which abdominal adhesions develop have remained unclear. Recent studies suggest that the main physiological mechanisms of adhesion are apoptosis and proliferation, oxidative stress, coagulation and fibrinolysis, and inflammatory responses [37]. In these roles, different cells play different roles. ...
Adhesions are the most common complication of abdominal or pelvic surgery and remain a challenging problem. To better understand the development tendency of abdominal adhesions, we performed a comprehensive bibliometric analysis of the field of abdominal adhesions. In total, 2219 articles regarding abdominal adhesions were screened and analyzed from 3410 manuscripts indexed in the Web of Science-indexed manuscripts regarding abdominal adhesion from 2004 to 2023. A bibliometric analysis was performed, and CiteSpace [version 6.2. R3 (64-bit)] and VOSviewer (version 1.6.19) were used to visualize the results. The number of annual publications showed slight growth before 2019, and the USA contributed the most publications. The most prolific author in this domain was Diamond, while the publications from Ten Broek had the strongest influence. The most popular journal in this field was the Journal of Surgical Research, and the most frequently co-cited journal was Fertility and Sterility. After analyzing the keywords, “prevention”, “surgery” and “peritoneal adhesion” were the 3 most co-cited keywords, while “adhesive small bowel obstruction” was the strongest keyword in the citation burst. Here, for the first time, we used bibliometric methods to study abdominal adhesions over the past ten years. By summarizing the characteristics of publications and predicting future research prospects, we established a framework for researchers and provided a basis for subsequent research.
... It effectively deterred fibroblast cell adherence, allowing the liver wound to heal normally without adhesion formation, and enabling easy separation from the liver [55,56]. Throughout the implantation period, the PEG molecules detached and were cleared by bodily fluids, facilitating mesothelial cell adherence and proliferation on the membrane surface [57]. This transition endowed the membrane with anti-adhesion properties, preventing adhesion between the membrane and abdominal wall. ...
In post-adhesion surgery, there is a clinical need for anti-adhesion membranes specifically designed for the liver, given the limited efficacy of current commercial products. To address this demand, we present a membrane suitable for liver surgery applications, fabricated through the modification of decellularized porcine pericardium with 20 KDa 8-arm PEGNHS. We also developed an optimized modification procedure to produce a high-performance anti-adhesion barrier. The modified membrane significantly inhibited fibroblast cell adherence while maintaining minimal levels of inflammation. By optimizing the modification ratio, we successfully controlled post-adhesion formation. Notably, the 8-arm PEG-modified pericardium with a molar ratio of 5 exhibited the ability to effectively prevent post-adhesion formation on the liver compared to both the control and Seprafilm®, with a low adhesion score of 0.5 out of 3.0. Histological analysis further confirmed its potential for easy separation. Furthermore, the membrane demonstrated regenerative capabilities, as evidenced by the proliferation of mesothelial cells on its surface, endowing anti-adhesion properties between the abdominal wall and liver. These findings highlight the membrane’s potential as a reliable barrier for repeated liver resection procedures that require the removal of the membrane multiple times.
... It has been recognised that three biological processes play a role in the formation of adhesion: coagulation cascade, fibrin degradation and inflammatory process (15). Traumas that trigger adhesion formation effect the peritoneum and lead to an inflammatory response, correspondingly; inflammation leads to the activation of fibrocoagulative pathways and formation of an exudate rich fibrin begins (16). If fibrin destruction can not occur through plasminogen and plasmin cascade, fibrous structures turn into collagen deposits. ...
... It has been recognised that three biological processes play a role in the formation of adhesion: coagulation cascade, fibrin degradation and inflammatory process (15). Traumas that trigger adhesion formation effect the peritoneum and lead to an inflammatory response, correspondingly; inflammation leads to the activation of fibrocoagulative pathways and formation of an exudate rich fibrin begins (16). If fibrin destruction can not occur through plasminogen and plasmin cascade, fibrous structures turn into collagen deposits. ...
Introduction: To determine the antiadhesive effects of bemiparine sodium compared to hyaluronic acid based jel on a standard adhesion
formation model of rat uterine horn.
Materials and Methods: Twenty non-pregnant female Sprague Dawley rats weighing 180-220 g were used to inflict a standardized model of adhesion formation on a rat uterine horn. The rats were randomized into four groups. Control group (group 1), bemiparin group (group 2), HA (hyaluronic acid) group (group 3) and bemiparin+hyaluronic acid group (group 4). Each group consisted of 5 animals. In all groups, ten standardized lesions were inflicted on the right uterine horn using bipolar cauterization with 10 watt power. The uterine horns of 20 rats were evaluated macroscopically, microscopically and with immunohistochemistry. For macroscopic evaluation; “adhesion type”, “adhesion tenacity”, “extent of adhesions” and “total macroscopic adhesion score” were determined. For microscopic evaluation; inflammation and fibrosis formation was evaluated. Immunohistochemistry scoring was performed utilizing VEGF (Vascular Endothelial Growth Factor) and TGF-β1 (Transformic Growth Factor beta-1) markers.
Results: Macroscopic adhesion scores, including “adhesion type”, “adhesion extent” and “total macroscopic adhesion score” in the bemiparin+HA group (group4) was significantly lower than those in the control group (group1) and group HA (group3) (p<0.05). Among these three categories;bemiparin +HA (group4) had a significantly lower score than group HA (group3) in terms of adhesion type (p<0,01) and bemiparin group (group2) had a lower score than HA group (group3) in in terms of adhesion extent (p<0,05). There were no statistical differences across all four groups for microscopic inflammation, fibrosis and immunohistochemistry staining.
Conclusion: The combined use of bemiparin and HA may be effective in preventing macroscopic pelvic adhesion formation. Clinical trials on humans should be conducted for further recommendations.
... The fluid is safe in combination with intestinal sutures, but it interferes with postoperative CT imaging due to the large amount of free fluid. Therefore, surgeons are somewhat wary of using these products on intestinal sutures, especially in sutures with an increased risk of leakage or in cases of massive contamination [14][15][16][17][18][19]. ...
Purpose of the Study: To analyze the effectiveness of using sodium deoxyribonucleate (SDN) for pelvic adhesions in rats in experiment. Materials and Methods: The experiment was carried out on 90 laboratory rats. Three groups of 30 animals each were formed: group 1-control; group 2-rats with a simulated adhesive process in the pelvis without subsequent treatment; group 3-animals with a model of adhesive process in the pelvis receiving intramuscular SDN for 10 days. The adhesive process in the pelvis was modeled in rats by ligating the uterine horns on both sides. The expression of CD4, CD8, CD20, CD138 was studied using DP-SOFT software program and subsequent statistical processing. Results: In animals of the control group, a small number of cells with expression of CD4 + , CD8 + and CD138 markers were found in the parietal peritoneum (PP). In perimetrium (PM), no positively stained cells of the studied immunophenotype were found. In group 2, animals showed an increase in the number of cells in the PP positively expressing CD4 + and CD138 + , and the appearance of CD56 + cells. An increase in the number of CD138 + and CD4 + cells was found in the rats' PM. In group 3, compared to the control, the count of CD4 + cells, CD56 + cells and CD138 + cells significantly increased. In the PM of the operated animals, we found an increase in the number of cells positively expressing CD4 + and CD138 + , and the appearance of CD56 + cells. In the PM of rats, an increase in the number of CD138 + and CD4 + cells was noted, which indicates activation of the humoral immune system. In group 3, the count of CD4 + , CD56 + and CD138 +-cells in the PP significantly increased compared to the control. PM was characterized by a similar distribution of cells. Conclusion: After surgery, the adhesive process causes a change in the ratio of leukocyte subpopulations in the affected area towards an increase in their number in the parietal peritoneum rather than in the perimetrium. The use of SDN has an immunomodulatory effect and stimulates immune responses by increasing the number of immunocompetent cells in the surgical site. archiv euromedica 2023 | vol. 13 | num. 6 | 1
... According to statistics, they have an incidence rate as high as 90 % [5]. Wound clots, mesothelial injuries, or foreign objects such as gauze are the leading causes of postoperative adhesions and abnormal fibrous connections between organs and surrounding tissues [6][7][8][9][10]. Almost every region of the body can develop postoperative adhesions, which can result in complications such as intestinal obstruction, reduced ventricular contractions, chronic pain, and female infertility [11][12][13]. ...
Abdominal adhesion is a frequent clinical issue with a high incidence rate and consequences following intra-abdominal surgery. Although many anti-adhesion materials have been used in surgical procedures, additional research is still needed to determine which ones have the most robust wet tissue adhesion, the best anti-postoperative adhesion, and the best anti-inflammatory properties. We have developed an excellent tissue adhesion and anti-swelling polyvinyl alcohol-chitosan hydrogel (AS hydrogel). According to in vitro cell testing, AS hydrogel significantly decreased inflammation around cells and exhibited good biocompatibility. Further, we assessed how well AS hydrogel prevented intraperitoneal adhesion using a rabbit model with cecum and abdominal wall injuries. According to the data, AS hydrogel has excellent anti-inflammatory and biodegradability properties compared to the control group. It can also prevent intestinal and abdominal wall injuries from occurring during surgery. Based on these results, hydrogel appears to be a perfect new material to prevent postoperative abdominal wall adhesion.
... During the remodeling process of the connective tissues after injury, the proliferation of fibroblasts may lead to matrix accumulation by increasing the production of collagen type I and III, unbalanced with the degradation [14]. Moreover, fibroblast dysfunction has been related with hypoxia [15]. ...
Diacutaneous Fibrolysis (DF) is an instrumentally assisted manual therapy technique defined as “a specific instrumental intervention for normalizing the musculoskeletal system function after a precise diagnosis and preserving the skin’s integrity”. The aim of this technique is soft tissue mobilization with the assistance of specially designed, hook-shaped steel instruments in different musculoskeletal structures, such as the myofascia, aponeurosis, tendons, ligaments and scar tissues. Due to discrepant results between previous reviews and the quite abundant new evidence provided by recently published randomized clinical trials, we propound this narrative review to provide an update on the scientific evidence related to the fundamentals and clinical efficacy of DF. Current evidence primarily supports the mechanical effect of DF on connective soft tissues. Diminished deep tendon reflex and rigidity have been registered after the implementation of DF in healthy subjects. Though there is still much to uncover, scientific evidence supports the use of the technique for the clinical treatment of subacromial impingement syndrome, chronic lateral epicondylalgia, chronic patellofemoral pain syndrome, mild to moderate carpal tunnel syndrome, hamstring shortening, temporomandibular disorders, tension-type headache and chronic low back pain. Additional data are essential for better recommendations in the clinical practice of DF.
... More challenging and convoluted to prevent than primary adhesion, recurrent postoperative adhesion was reported to have a higher rate of 80% owing to the vicious circle of adhesiolysis surgery, which indicates an urgent demand for timely non-invasive intervention of PA based on biological and genetic innovation in modulating the healing response [14,15]. With in-depth research of the mechanism of PA formation, multiple drug treatments have been explored to reduce peritendinous adhesion without compromising tendon healing and thus achieve better gliding function of regenerated tendon [16][17][18]. Unfortunately, there remains a gap between drug discovery and clinical applications that numerous anti-adhesion drugs have only been curative in animal experiments but have not yet achieved satisfactory clinical results and even exerted adverse effects on tendon healing [19][20][21]. ...
Peritendinous adhesion (PA) is one of the most common complications following hand surgery and characterized with abnormal hyperplasia of connective tissue and excessive deposition of extracellular matrix. Subsequently, various clinical symptoms such as chronic pain, limb dyskinesia and even joint stiffness occur and patients are always involved in the vicious cycle of “adhesion – release – re-adhesion”, which seriously compromise the quality of life. Until present, the underlying mechanism remains controversial and lack of specific treatment, with symptomatic treatment being the only option to relieve symptoms, but not contributing no more to the fundamentally rehabilitation of basic structure and function. Recently, novel strategies have been proposed to inhibit the formation of adhesion tissues including implantation of anti-adhesion barriers, anti-inflammation, restraint of myofibroblast transformation and regulation of collagen overproduction. Furthermore, gene therapy has also been considered as a promising anti-adhesion treatment. In this review, we provide an overview of anti-adhesion targets and relevant drugs to summarize the potential pharmacological roles and present subsequent challenges and prospects of anti-adhesion drugs.
