Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion.

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.

Effect of pre-incisional and peritoneal local anesthetics administration on colon anastomosis and wound healing.

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.

Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats.

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.

Use of mixed gas pneumoperitoneum during minimally invasive surgery: a systematic review of human and mouse modelled laparoscopic interventions.

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.

Hemoadhican-Based Bioabsorbable Hydrogel for Preventing Postoperative Adhesions.

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.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

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.

Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

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.

Intrauterine interventions options for preventing recurrence after hysteroscopic adhesiolysis: a systematic review and network meta-analysis of randomized controlled trials.

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.

Laparoscopic application of sodium hyaluronate-carboxymethylcellulose barrier in abdominopelvic surgery: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Systematic Review Protocols-compliant systematic review and meta-analysis.

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.

Multi-functional dual-layer nanofibrous membrane for prevention of postoperative pancreatic leakage.

Postoperative pancreatic leakage due to pancreatitis in patients is a life-threatening surgical complication. The majority of commercial barriers are unable to meet the demands for pancreatic leakage due to poor adhesiveness, toxicity, and inability to degrade. In this study, we fabricated mitomycin-c and thrombin-loaded multifunctional dual-layer nanofibrous membrane with a combination of alginate, PCL, and gelatin to resolve the leakage due to suture line disruption, promote hemostasis, wound healing, and prevent postoperative tissue adhesion. Electrospinning was used to fabricate the dual-layer system. The study results demonstrated that high gelatin and alginate content in the inner layer decreased the fiber diameter and water contact angle, and crosslinking allowed the membrane to be more hydrophilic, making it highly biodegradable, and adhering firmly to the tissue surfaces. The results of in vitro biocompatibility and hemostatic assay revealed that the dual-layer had a higher cell proliferation and showed effective hemostatic properties. Moreover, the in vivo studies and in silico molecular simulation indicated that the dual layer was covered at the wound site, prevented suture disruption and leakage, inhibited hemorrhage, and reduced postoperative tissue adhesion. Finally, the study results proved that dual-layer multifunctional nanofibrous membrane has a promising therapeutic potential in preventing postoperative pancreatic leakage.

Instant tough adhesion of polymer networks.

Generating strong rapid adhesion between hydrogels has the potential to advance the capabilities of modern medicine and surgery. Current hydrogel adhesion technologies rely primarily on liquid-based diffusion mechanisms and the formation of covalent bonds, requiring prolonged time to generate adhesion. Here, we present a simple and versatile strategy using dry chitosan polymer films to generate instant adhesion between hydrogel-hydrogel and hydrogel-elastomer surfaces. Using this approach we can achieve extremely high adhesive energies (>3,000 J/m2), which are governed by pH change and non-covalent interactions including H-bonding, Van der Waals forces, and bridging polymer entanglement. Potential examples of biomedical applications are presented, including local tissue cooling, vascular sealing, prevention of surgical adhesions, and prevention of hydrogel dehydration. We expect these findings and the simplicity of this approach to have broad implications for adhesion strategies and hydrogel design.

Investigation of anti-adhesion ability of 8-arm PEGNHS-modified porcine pericardium.

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 hexaglycerol octa (succinimidyloxyglutaryl) polyoxyethylene (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.

Designing a bi-layer multifunctional hydrogel patch based on polyvinyl alcohol, quaternized chitosan and gallic acid for abdominal wall defect repair.

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.

Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers.

Tissue adhesion is one of the most common postoperative complications, which is frequently accompanied by inflammation, pain, and even dyskinesia, significantly reducing the quality of life of patients. Thus, to prevent the formation of tissue adhesions, various strategies have been explored. Among these methods, placing anti-adhesion membranes over the injured site to separate the wound from surrounding tissues is a simple and prominently favored method. Recently, electrospun nanofibers have been the most frequently investigated antiadhesive membranes due to their tunable porous structure and high porosities. They not only can act as an essential barrier and functional carrier system but also allow for high permeability and nutrient transport, showing great potential for preventing tissue adhesion. Herein, we provide a short review of the most recent applications of electrospun nanofibrous antiadhesive membranes in tendons, the abdominal cavity, dural sac, pericardium, and meninges. Firstly, each section highlights the most representative examples and they are sorted based on the latest progress of related research. Moreover, the design principles, preparation strategies, overall performances, and existing problems are highlighted and evaluated. Finally, the current challenges and several future ways to develop electrospun nanofibrous antiadhesive membranes are proposed. The systematic discussion and proposed directions can shed light on ideas and guide the reasonable design of electrospun nanofibrous membranes, contributing to the development of exceptional tissue anti-adhesive materials in the foreseeable future.

The Determination of the Biocompatibility of New Compositional Materials, including Carbamide-Containing Heterocycles of Anti-Adhesion Agents for Abdominal Surgery.

Due to traumatic injuries, including those from surgical procedures, adhesions occur in over 50% of cases, necessitating exclusive surgical intervention for treatment. However, preventive measures can be implemented during abdominal organ surgeries. These measures involve creating a barrier around internal organs to forestall adhesion formation in the postoperative phase. Yet, the effectiveness of the artificial barrier relies on considerations of its biocompatibility and the avoidance of adverse effects on the body. This study explores the biocompatibility aspects, encompassing hemocompatibility, cytotoxicity, and antibacterial and antioxidant activities, as well as the adhesion of blood serum proteins and macrophages to the surface of new composite film materials. The materials, derived from the sodium salt of carboxymethylcellulose modified by glycoluril and allantoin, were investigated. The research reveals that film materials with a heterocyclic fragment exhibit biocompatibility comparable to commercially used samples in surgery. Notably, film samples developed with glycoluril outperform the effects of commercial samples in certain aspects.

A Laparoscopically Compatible Rapid-Adhesion Bioadhesive for Asymmetric Adhesion, Non-Pressing Hemostasis, and Seamless Seal.

Bioadhesive hydrogels offer unprecedented opportunities in hemostatic agents and tissue sealing; however, the application of existing bioadhesive hydrogels through narrow spaces to achieve strong adhesion in fluid-rich physiological environments is challenged either by undesired indiscriminate adhesion or weak wet tissue adhesion. Here, a laparoscopically compatible asymmetric adhesive hydrogel (aAH) composed of sprayable adhesive hydrogel powders and injectable anti-adhesive glue is proposed for hemostasis and to seal the bloody tissues in a non-pressing way, allowing for preventing postoperative adhesion. The powders can seed on the irregular bloody wound to rapidly absorb interfacial fluid, crosslink, and form an adhesive hydrogel to hemostatic seal (blood clotting time and tissue sealing in 10 s, ≈200 mm Hg of burst pressure in sealed porcine tissues). The aAH can be simply formed by crosslinking the upper powder with injectable glue to prevent postoperative adhesion (adhesive strength as low as 1 kPa). The aAH outperforms commercial hemostatic agents and sealants in the sealing of bleeding organs in live rats, demonstrating superior anti-adhesive efficiency. Further, the hemostatic seamless sealing by aAH succeeds in shortening the time of warm ischemia, decreasing the blood loss, and reducing the possibility of rebleeding in the porcine laparoscopic partial nephrectomy model.

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

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

Inhibition of chemokine receptor CXCR2 attenuates postoperative peritoneal adhesion formation.

BACKGROUND: Postoperative peritoneal adhesions remain a problem after general and gynecological surgery. METHODS: Hematoxylin and eosin and Masson's trichrome staining of ischemic buttons were performed 6, 12, 24 hours, and 7 days after button induction. Scanning electron microscopy, ribonucleic acid sequencing, quantitative real-time polymerase chain reaction, immunohistochemical staining, and flow cytometry were used to elucidate the pathophysiology of postoperative peritoneal adhesions. RESULTS: The results showed that thickening of the peritoneum and abscission of mesothelial cells and collagen fibers increased significantly on the surface of the "button" in the control groups at 24 hours postoperatively. Scanning electron microscopy revealed a large number of granulocytes on the button surface in the control group at 24 hours. Ribonucleic acid sequencing and quantitative real-time polymerase chain reaction also revealed that CXCR2 expression was significantly upregulated. In addition, danirixin, a CXCR2 inhibitor, reduced abdominal adhesion in the injured area by inhibiting the infiltration of inflammatory cells and collagen production. Immunohistochemical staining showed decreased expression of CXCR2 in the adhesion area 7 days after surgery in the treatment group. Flow cytometry showed a significantly decreased neutrophil ratio in the treatment group compared with that in the control group 24 hours after the operation. CONCLUSIONS: Inflammation plays an important role in the early stages of postoperative peritoneal adhesion formation, whereas collagen fibers and angiogenesis play important roles in the late stages. The CXCL2-CXCL3-CXCR2 signaling axis is an important link in the mechanism of postoperative peritoneal adhesion formation, and the application of CXCR2 inhibitors can alleviate the formation of postoperative peritoneal adhesions.

Injectable Multifunctional Composite Hydrogel as a Combination Therapy for Preventing Postsurgical Adhesion.

Postsurgical adhesion (PA) is a common and serious postoperative complication that affects millions of patients worldwide. However, current commercial barrier materials are insufficient to inhibit diverse pathological factors during PA formation, and thus, highly bioactive materials are needed. Here, this work designs an injectable multifunctional composite hydrogel that can serve as a combination therapy for preventing PA. In brief, this work reveals that multiple pathological events, such as chronic inflammatory and fibrotic processes, contribute to adhesion formation in vivo, and such processes can not be attenuated by barrier material (e.g., hydrogel) alone treatments. To solve this limitation, this work designs a composite hydrogel made of the cationic self-assembling peptide KLD2R and TGF-ß receptor inhibitor (TGF-ßRi)-loaded mesenchymal stem cell-derived nanovesicles (MSC-NVs). The resulting composite hydrogel displays multiple functions, including physical separation of the injured tissue areas, antibacterial effects, and local delivery and sustained release of anti-inflammatory MSC-NVs and antifibrotic TGF-ßRi. As a result, this composite hydrogel effectively inhibited local inflammation, fibrosis and adhesion formation in vivo. Moreover, the hydrogel also exhibits good biocompatibility and biodegradability in vivo. Together, the results highlight that this "all-in-one" composite hydrogel strategy may provide insights into designing advanced therapies for many types of tissue injury.

Super-Structured Wet-Adhesive Hydrogel with Ultralow Swelling, Ultrahigh Burst Pressure Tolerance, and Anti-Postoperative Adhesion Properties for Tissue Adhesion.

Wet-adhesive hydrogels have been developed as an attractive strategy for tissue repair. However, achieving simultaneously low swelling and high burst pressure tolerance of wet-adhesive hydrogels is crucial for in vivo application which remains challenges. Herein, a novel super-structured porous hydrogel (denoted as PVA/PAAc-N+ ) is designed via facile moisture-induced phase separation-solvent exchange process for obtaining porous polyvinyl alcohol (PVA) hydrogel as dissipative layer and in situ photocuring technology for entangling quaternary ammonium-functionalized poly(acrylic acid)-based wet-adhesive layer (PAAc-N+ ) with the porous surface of PVA layer. Benefitting from the ionic crosslinking between quaternary ammonium ions and carboxylate ions in PAAc-N+ wet-adhesive layer as well as the high crystallinity induced by abundant hydrogen bonds of PVA layer, the hydrogel has unique ultralow swelling property (0.29) without sacrificing adhesion strength (63.1 kPa). The porous structure of PVA facilitates the mechanical interlock at the interface between PAAc-N+ wet-adhesive layer and tough PVA dissipative layer, leading to the ultrahigh burst pressure tolerance up to 493 mm Hg and effective repair for porcine heart rupture; the PVA layer surface of PVA/PAAc-N+ hydrogel can prevent postoperative adhesion. By integrating ultralow swelling, ultrahigh burst pressure tolerance, and anti-postoperative adhesion properties, PVA/PAAc-N+ hydrogel shows an appealing application prospect for tissue repair.