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1.
Sci Rep ; 14(1): 11077, 2024 05 14.
Article En | MEDLINE | ID: mdl-38745015

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.


Everolimus , Prednisolone , Animals , Everolimus/pharmacology , Everolimus/administration & dosage , Tissue Adhesions/drug therapy , Tissue Adhesions/prevention & control , Tissue Adhesions/pathology , Prednisolone/pharmacology , Prednisolone/administration & dosage , Rats , Male , Drug Therapy, Combination , Disease Models, Animal , Peritoneum/pathology , Peritoneum/drug effects , Peritoneal Diseases/drug therapy , Peritoneal Diseases/pathology , Peritoneal Diseases/prevention & control , Peritoneal Diseases/etiology , Postoperative Complications/prevention & control , Postoperative Complications/drug therapy
2.
Khirurgiia (Mosk) ; (5): 86-94, 2024.
Article Ru | MEDLINE | ID: mdl-38785243

OBJECTIVE: The purpose of the study was to evaluate the results of using fluoropolymer-coated mesh during intraperitoneal onlay mesh hernia repair in patients with primary ventral hernias. MATERIAL AND METHODS: The multicenter, non-randomized, controlled clinical study included 88 patients of both sexes who were operated on using a laparoscopic approach using the IPOM technique for a primary ventral hernia. The duration of observation ranged from 3 to 12 months. In the main group, 48 patients received fluoropolymer-coated meshes (Ftorex). A comparison was made with a retrospective group of 40 patients who were treated with anti-adhesive collagen-coated meshes (Parietene composite, Parietex Composite, Symbotex). RESULTS: The number of early and late postoperative complications in the groups did not have significant differences, at the same time, their number was lower in the group of patients in whom fluoropolymer-coated meshes were used. Most of the complications corresponded to Clavien-Dindo class I and II and did not pose a significant threat to health. There were no recurrences of hernias observed in patients included in the study. There were slightly more adhesions in the fluoropolymer-coated mesh group (35.4% vs. 25.0% in the collagen-coated mesh group). The quality of life of patients in the study groups did not differ. CONCLUSION: In laparoscopic IPOM hernia repair fluoropolymer-coated meshes are not inferior in effectiveness and safety to traditionally used collagen-coated meshes and can be recommended for use in patients with primary ventral hernias.


Hernia, Ventral , Herniorrhaphy , Laparoscopy , Postoperative Complications , Surgical Mesh , Humans , Hernia, Ventral/surgery , Male , Female , Laparoscopy/methods , Middle Aged , Herniorrhaphy/methods , Herniorrhaphy/adverse effects , Herniorrhaphy/instrumentation , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Tissue Adhesions/prevention & control , Adult , Coated Materials, Biocompatible , Treatment Outcome , Aged , Retrospective Studies , Fluorocarbon Polymers , Russia
3.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Article En | MEDLINE | ID: mdl-38695772

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Nanofibers , Animals , Rats , Nanofibers/chemistry , Wound Healing/drug effects , Reactive Oxygen Species/metabolism , Skin/drug effects , Skin/pathology , Tissue Adhesions/prevention & control , Rats, Sprague-Dawley , Cell Adhesion/drug effects , Cerium/chemistry , Cerium/pharmacology , Surface Properties , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
4.
J Colloid Interface Sci ; 670: 486-498, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38772264

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.


Dendrimers , Hydrogels , Meloxicam , Nylons , Polyglutamic Acid , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Polyglutamic Acid/chemistry , Polyglutamic Acid/pharmacology , Polyglutamic Acid/analogs & derivatives , Nylons/chemistry , Tissue Adhesions/prevention & control , Dendrimers/chemistry , Dendrimers/pharmacology , Meloxicam/chemistry , Meloxicam/pharmacology , Meloxicam/administration & dosage , Mice , Inflammation/prevention & control , Inflammation/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Rats , Rats, Sprague-Dawley , Fibrinolysis/drug effects , Postoperative Complications/prevention & control , Particle Size , Injections , Drug Carriers/chemistry
5.
Transfusion ; 64(6): 1059-1067, 2024 Jun.
Article En | MEDLINE | ID: mdl-38693056

BACKGROUND: Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)-based therapies. METHODS: Forty-four (n = 44) male Sprague-Dawley rats (250-350 g) were used in the experiment. Of these, thirty-eight (n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 106 cells/10 mL Plasmalyte A), hPSC-CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post-operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison. RESULTS: The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC-CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT. DISCUSSION: The presented rat model and scoring system represent the clinical adhesion disease process. hPSC-based interventions significantly reduce abdominal adhesions in this pilot dataset.


Rats, Sprague-Dawley , Tissue Adhesions/prevention & control , Animals , Humans , Rats , Female , Pilot Projects , Male , Pregnancy , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Disease Models, Animal , Placenta/cytology , Stem Cell Transplantation/methods , Stem Cells/cytology
6.
J Robot Surg ; 18(1): 215, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758349

The formation of pneumoperitoneum involves the process of inflating the peritoneal cavity during laparoscopic and typically uses CO2 as the insufflation gas. This review aims to identify ideal gas mixtures for establishing the pneumoperitoneum with animal and human studies undertaken up to the writing of this review. A systematic search of PubMed, OVID, and clinicaltrials.gov was performed to identify studies on the utilisation of mixed gases in laparoscopic surgery, including non-randomised/randomised trials, animal and human studies, and studies with inflating pressures between 12 and 16 mmHg. ROBINS-I and RoB2 tool was used to assess the risk of bias. A narrative synthesis of results was performed due to the heterogeneity of the studies. 5 studies from the database search and 5 studies from citation search comprising 128 animal subjects and 61 human patients were found. These studies collated results based on adhesion formation (6 studies), pain scores (2 studies) and other outcomes, with results favouring the use of carbon dioxide + 10% nitrous oxide + 4% oxygen. This has shown a significant reduction in adhesion formation, pain scores and inflammation. The use of this gas mixture provides promising results for future practice. Several of the studies available require larger sample sizes to develop a more definitive answer on the effects of different gas mixtures. Furthermore, the number of confounding factors in randomised trials should be reduced so that each component of the current suggested gas mixture can be tested for safety and efficacy.


Carbon Dioxide , Laparoscopy , Nitrous Oxide , Pneumoperitoneum, Artificial , Animals , Humans , Mice , Carbon Dioxide/administration & dosage , Insufflation/methods , Laparoscopy/methods , Minimally Invasive Surgical Procedures/methods , Models, Animal , Nitrous Oxide/administration & dosage , Oxygen/administration & dosage , Pneumoperitoneum, Artificial/methods , Pneumoperitoneum, Artificial/adverse effects , Tissue Adhesions/prevention & control
7.
Int J Colorectal Dis ; 39(1): 79, 2024 May 26.
Article En | MEDLINE | ID: mdl-38797803

BACKGROUND: Empty Pelvis Syndrome, subsequent to the removal of pelvic organs, results in the descent of the small bowel into an inflamed pelvic cavity, leading to the formation of adhesions and subsequent small bowel obstruction. However, no effective measures have been previously described. OBJECTIVE: Describe a simple and autologous solution to prevent "Empty Pelvis Syndrome," small bowel obstruction, and adhesions by utilizing the cecum to occlude the pelvis. DESIGN: Mobilization of the right colon to lower the cecum into the pelvic cavity to occlude the superior pelvic ring to some degree and changing the direction of the terminal ileum. SETTINGS: Hospital Universitario Fundación Jiménez Díaz, Department of General Surgery, Colorectal Service. PATIENTS: Eight anonymized patients were included in this study, each with varying colorectal pathologies. Patients were above 18 years old. MAIN OUTCOME MEASURES: Percent of blockage of the superior pelvic ring produced by the descended cecum recorded in percentage; the amount of small intestine descended past the superior pelvic ring recorded in cm. RESULTS: The mobilization of the cecum achieved partial occlusion of the superior pelvic ring. The descent of the small bowel beyond this landmark ranged from 0 to 4.9 cm. LIMITATIONS: Given the small number of patients included in this study, these results cannot be generalized to the whole of the population. A bladder emptying protocol prior to CT scans was not implemented, resulting in variations in measurements among patients. CONCLUSION: The cecum-to-pelvis technique is a simple method that can serve as an autologous solution to EPS (enteropelvic fistula) and help reduce postoperative complications such as SBO (small bowel obstruction) and adhesions. It is not essential to completely occlude the superior pelvic ring to achieve successful outcomes.


Cecum , Pelvis , Postoperative Complications , Humans , Cecum/surgery , Pelvis/surgery , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Female , Male , Middle Aged , Tissue Adhesions/prevention & control , Tissue Adhesions/etiology , Adult , Intestinal Obstruction/prevention & control , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Aged
8.
J Ethnopharmacol ; 331: 118290, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38703872

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. AIM OF THE STUDY: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. METHODS: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. RESULTS: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. CONCLUSION: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.


Drugs, Chinese Herbal , Macrophages , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , c-Mer Tyrosine Kinase , Animals , Proto-Oncogene Proteins c-akt/metabolism , Drugs, Chinese Herbal/pharmacology , Mice , c-Mer Tyrosine Kinase/metabolism , Signal Transduction/drug effects , Male , Macrophages/drug effects , Macrophages/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Tissue Adhesions/prevention & control , Tissue Adhesions/metabolism , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Disease Models, Animal
9.
Ulus Travma Acil Cerrahi Derg ; 30(5): 316-322, 2024 May.
Article En | MEDLINE | ID: mdl-38738675

BACKGROUND: Previous research has shown that levobupivacaine is as effective as bupivacaine but carries a lower risk of cardiac and central nervous system toxicity. This study explores whether levobupivacaine and bupivacaine are preferable for all patients, includ-ing those with comorbidities, particularly focusing on their effects on colonic anastomosis. The primary objective is to examine the influence of levobupivacaine and bupivacaine on colonic anastomosis. Additionally, the study will assess their impact on wound healing and their anti-adhesive properties. METHODS: Conducted between July 28, 2022, to August 4, 2022, at the Hamidiye Animal Experiments Laboratory, this study was approved by the University Science Health, Hamidiye Animal Experiments Local Ethics Committee. This study was conducted using 21 male Sprague rats aged 16-20 weeks. The rats were allocated into three equal groups of seven each: Group C: pre-incisional isotonic; Group B: pre-incisional bupivacaine; and Group L: pre-incisional levobupivacaine. Macroscopic adhesion scores (MAS) were recorded during laparotomy and tissue samples were taken for histopathological examination and hydroxyproline levels measurement. Wound tensile strength along the middle incision line and anastomotic burst pressure were also assessed. RESULTS: MAS was statistically significantly lower in Groups B and L compared to Group C (p<0.001). The wound histopathology score (WHS) was significantly higher in Group L than in Group B (p=0.021). Colon histopathology scores (CHSs) were also signifi-cantly higher in Group L compared to Group C (p=0.011). CONCLUSION: TThe study found that bupivacaine and levobupivacaine did not significantly enhance wound healing, although le-vobupivacaine significantly improved WHS relative to bupivacaine. According to the findings of this study, levobupivacaine can enhance clinical practice by being used in patients undergoing colon anastomosis. It contributes significantly to the durability of colon anasto-mosis, has a more positive effect on wound healing compared to bupivacaine, and exhibits anti-adhesive properties. Additional clinical trials are necessary to validate these results further.


Anastomosis, Surgical , Anesthetics, Local , Bupivacaine , Colon , Levobupivacaine , Rats, Sprague-Dawley , Wound Healing , Animals , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Male , Rats , Wound Healing/drug effects , Colon/surgery , Colon/pathology , Levobupivacaine/administration & dosage , Bupivacaine/analogs & derivatives , Bupivacaine/administration & dosage , Bupivacaine/pharmacology , Tissue Adhesions/prevention & control
10.
Int J Biol Macromol ; 270(Pt 1): 132061, 2024 Jun.
Article En | MEDLINE | ID: mdl-38705326

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.


Hyaluronic Acid , Polypropylenes , Polyvinyl Alcohol , Surgical Mesh , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Polyvinyl Alcohol/chemistry , Animals , Polypropylenes/chemistry , Rats , Tissue Adhesions/prevention & control , Hydrogels/chemistry , Hydrogels/pharmacology , Male , Abdominal Wall/surgery , Humans , Rats, Sprague-Dawley , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Materials Testing , Herniorrhaphy/methods
11.
ACS Appl Mater Interfaces ; 16(14): 17267-17284, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38556996

Postoperative peritoneal adhesions are a prevalent clinical issue following abdominal and pelvic surgery, frequently resulting in heightened personal and societal health burdens. Traditional biomedical barriers offer limited benefits because of practical challenges for doctors and their incompatibility with laparoscopic surgery. Hydrogel materials, represented by hyaluronic acid gels, are receiving increasing attention. However, existing antiadhesive gels still have limited effectiveness or carry the risk of complications in clinical applications. Herein, we developed a novel hydrogel using polysaccharide hemoadhican (HD) as the base material and polyethylene glycol diglycidyl ether (PEGDE) as the cross-linking agent. The HD hydrogels exhibit appropriate mechanical properties, injectability, and excellent cytocompatibility. We demonstrate resistance to protein adsorption and L929 fibroblast cell adhesion to the HD hydrogel. The biodegradability and efficacy against peritoneal adhesion are further evaluated in C57BL/6 mice. Our results suggest a potential strategy for anti-postoperative tissue adhesion barrier biomaterials.


Absorbable Implants , Hydrogels , Rats , Mice , Animals , Hydrogels/pharmacology , Rats, Sprague-Dawley , Tissue Adhesions/prevention & control , Mice, Inbred C57BL , Postoperative Complications/prevention & control
12.
Reprod Biol Endocrinol ; 22(1): 49, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38654308

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.


Hysteroscopy , Infertility, Female , Intrauterine Devices , Pregnancy Outcome , Humans , Female , Tissue Adhesions/prevention & control , Adult , Pregnancy , Hysteroscopy/methods , Infertility, Female/therapy , Infertility, Female/etiology , Infertility, Female/prevention & control , Prospective Studies , Uterine Diseases/surgery , Uterine Diseases/complications , Uterine Diseases/prevention & control , Uterine Diseases/pathology , Treatment Outcome , Pregnancy Rate
13.
Adv Mater ; 36(21): e2308921, 2024 May.
Article En | MEDLINE | ID: mdl-38588501

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.


Cell Adhesion Molecules , Disease Models, Animal , Endometrium , Exosomes , Fibrosis , Hydrogels , Macrophage Activation , Animals , Female , Endometrium/pathology , Endometrium/metabolism , Mice , Cell Adhesion Molecules/metabolism , Hydrogels/chemistry , Exosomes/metabolism , Exosomes/chemistry , Macrophage Activation/drug effects , Macrophages/metabolism , Tissue Adhesions/prevention & control , RAW 264.7 Cells
14.
ACS Biomater Sci Eng ; 10(5): 3164-3172, 2024 May 13.
Article En | MEDLINE | ID: mdl-38671385

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.


Dexamethasone , Drug Delivery Systems , Hydrogels , Nanofibers , Polylactic Acid-Polyglycolic Acid Copolymer , Nanofibers/chemistry , Nanofibers/therapeutic use , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/administration & dosage , Tissue Adhesions/prevention & control , Animals , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Dexamethasone/pharmacology , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Chitosan/chemistry , Chitosan/pharmacology , Intestines/drug effects , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Postoperative Complications/prevention & control , Rats, Sprague-Dawley , Mice , Female , Rats
15.
Arch Gynecol Obstet ; 309(5): 1847-1861, 2024 May.
Article En | MEDLINE | ID: mdl-38493418

PURPOSE: Recurrence of adhesions after hysteroscopic adhesiolysis is a challenging clinical problem without a unified management approach. Therefore, we conducted a network meta-analysis that considered both direct and indirect comparisons between interventions to identify optimal strategies for preventing recurrence. METHODS: We searched for research trials published up to July 2023 from PubMed, Embase and the Cochrane Database. We selected randomized controlled trials comparing the use of different interventions for the prevention of adhesion recurrence, with no language or regional restrictions. We used random-effects models to assess odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CI). Adverse events associated with the interventions were also assessed. This study was registered on PROSPERO, CRD42023449068. RESULTS: Data from 21 randomized controlled trials involving 2406 patients were synthesized, including interventions with balloon, amnion, platelet-rich plasma (PRP), intrauterine device (IUD), hyaluronic acid (HA), platelet-rich fibrin (PRF), and granulocyte colony-stimulating factor (G-CSF). The top 5 interventions for change in AFS scores were: PRP + Balloon (MD = 5.44; 95% CI, 2.63-8.25), Amnion + Balloon (MD = 5.08; 95% CI, 2.71-7.44), IUD + Balloon (MD = 4.89; 95% CI, 2.49-7.30), HA + Balloon (MD = 3.80; 95% CI, 1.78-5.82), and G-CSF + Balloon (MD = 3.84; 95% CI, 1.05-6.63). There were no statistically significant differences between interventions in the recurrence rate of moderate-to-severe uterine adhesions and the clinical pregnancy rate. Most interventions were safe. CONCLUSIONS: To our knowledge, this is the most comprehensive network meta-analysis to date of interventions for preventing postoperative intrauterine adhesion recurrence. Our results indicate that PRP + Balloon seems to be the most effective approach.


Hysteroscopy , Uterine Diseases , Pregnancy , Female , Humans , Hysteroscopy/adverse effects , Network Meta-Analysis , Randomized Controlled Trials as Topic , Uterine Diseases/surgery , Hyaluronic Acid/therapeutic use , Tissue Adhesions/prevention & control , Tissue Adhesions/surgery , Tissue Adhesions/etiology , Granulocyte Colony-Stimulating Factor
16.
Surgery ; 175(5): 1358-1367, 2024 May.
Article En | MEDLINE | ID: mdl-38429164

BACKGROUND: We aimed to evaluate the incidence of postoperative adhesion formation and adhesion-related consequences (eg, bowel obstruction) after placement of a sodium hyaluronate-carboxymethylcellulose adhesion barrier after laparoscopic abdominopelvic surgery. METHODS: In this systematic review and meta-analysis, we searched the Medical Literature Analysis and Retrieval System Online and Embase via Ovid, Cochrane Central Register of Controlled Trials, ScienceDirect, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, and Clinical Trial Registries. A manual search (eg, Google Scholar and professional association websites) was also conducted to supplement the electronic database results. Two reviewers independently identified relevant studies based on inclusion and exclusion criteria and extracted data. RESULTS: A total of 28 studies were included in the systematic qualitative review. Three of the 28 studies included had comparable outcome measures, interventions, and control groups, allowing the pooling of study data. A total of 938 patients (490 patients in the sodium hyaluronate-carboxymethylcellulose barrier group and 448 in the no adhesion barrier group) from these 3 studies were included in the meta-analyses, which found the incidence of bowel obstruction was significantly lower (65% risk reduction) in the sodium hyaluronate-carboxymethylcellulose barrier group compared with the control group (relative risk = 0.35; 95% confidence interval, 0.19-0.63; P = .005) with extremely low heterogeneity between studies (I2 = 0; P = .41). The placement of sodium hyaluronate-carboxymethylcellulose barrier laparoscopically did not create new safety signals nor did it increase the incidence of adverse events. CONCLUSION: Our meta-analysis found that laparoscopic application of a sodium hyaluronate-carboxymethylcellulose barrier in abdominopelvic surgery reduces the risk of bowel obstruction where applied during the early postoperative phase.


Intestinal Obstruction , Laparoscopy , Humans , Hyaluronic Acid/therapeutic use , Carboxymethylcellulose Sodium/therapeutic use , Systematic Reviews as Topic , Laparoscopy/adverse effects , Tissue Adhesions/epidemiology , Tissue Adhesions/etiology , Tissue Adhesions/prevention & control , Meta-Analysis as Topic
17.
Adv Mater ; 36(21): e2309655, 2024 May.
Article En | MEDLINE | ID: mdl-38517062

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.


Colorectal Neoplasms , Membrane Proteins , Neoplasm Recurrence, Local , Xanthones , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Animals , Humans , Membrane Proteins/metabolism , Mice , Neoplasm Recurrence, Local/prevention & control , Xanthones/chemistry , Xanthones/pharmacology , Cell Line, Tumor , Tissue Adhesions/prevention & control , Membranes, Artificial , Prodrugs/chemistry , Prodrugs/pharmacology , Reactive Oxygen Species/metabolism , Hyaluronic Acid/chemistry
18.
Curr Pharm Des ; 30(11): 859-867, 2024.
Article En | MEDLINE | ID: mdl-38468533

BACKGROUND: Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model. METHODS: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods. RESULTS: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs. CONCLUSION: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.


Angiotensin-Converting Enzyme Inhibitors , Drug Repositioning , Animals , Rats , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Tissue Adhesions/prevention & control , Tissue Adhesions/pathology , Male , Rats, Sprague-Dawley , Achilles Tendon/drug effects , Achilles Tendon/pathology , Achilles Tendon/surgery , Disease Models, Animal
19.
J Control Release ; 369: 573-590, 2024 May.
Article En | MEDLINE | ID: mdl-38554773

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect-cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.


GATA6 Transcription Factor , Hyaluronic Acid , Hydrogels , Macrophages , Postoperative Complications , Reactive Oxygen Species , Tissue Adhesions/prevention & control , Animals , Hydrogels/chemistry , Hydrogels/administration & dosage , Macrophages/drug effects , Macrophages/metabolism , Reactive Oxygen Species/metabolism , Hyaluronic Acid/chemistry , Postoperative Complications/prevention & control , GATA6 Transcription Factor/metabolism , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/administration & dosage , Catechin/pharmacology , Rats, Sprague-Dawley , Mice , Adipates/chemistry , Male , Abdomen/surgery , RAW 264.7 Cells , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Drug Liberation
20.
Int J Biol Macromol ; 263(Pt 1): 130291, 2024 Apr.
Article En | MEDLINE | ID: mdl-38378119

In abdominal wall defect repair, surgical site infection (SSI) remains the primary cause of failure, while complications like visceral adhesions present significant challenges following patch implantation. We designed a Janus multifunctional hydrogel patch (JMP) with antibacterial, anti-inflammatory, and anti-adhesive properties. The patch comprises two distinct layers: a pro-healing layer and an anti-adhesion layer. The pro-healing layer was created by a simple mixture of polyvinyl alcohol (PVA), quaternized chitosan (QCS), and gallic acid (GA), crosslinked to form PVA/QCS/GA (PQG) hydrogels through GA's self-assembly effect and hydrogen bonding. Additionally, the PVA anti-adhesive layer was constructed using a drying-assisted salting method, providing a smooth and dense physical barrier to prevent visceral adhesion while offering essential mechanical support to the abdominal wall. The hydrogel patch demonstrates widely adjustable mechanical properties, exceptional biocompatibility, and potent antimicrobial properties, along with a sustained and stable release of antioxidants. In rat models of skin and abdominal wall defects, the JMP effectively promoted tissue healing by controlling infection, inhibiting inflammation, stimulating neovascularization, and successfully preventing the formation of visceral adhesions. These compelling results highlight the JMP's potential to improve the success rate of abdominal wall defect repair and reduce surgical complications.


Abdominal Wall , Chitosan , Rats , Animals , Hydrogels/pharmacology , Polyvinyl Alcohol , Gallic Acid , Abdominal Wall/surgery , Anti-Bacterial Agents/pharmacology , Adhesives , Tissue Adhesions/prevention & control
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