Antioxidant Carbon Dots and Ursolic Acid Co-Encapsulated Liposomes Composite Hydrogel for Alleviating Adhesion Formation and Enhancing Tendon Healing in Tendon Injury.

Background: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury. Materials and Methods: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury. Results: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased. Conclusion: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.

A novel intrauterine estrogen-releasing system for preventing the postoperative recurrence of intrauterine adhesion: a multicenter randomized controlled study.

BACKGROUND: Transcervical resection of adhesions (TCRA) is the standard treatment for intrauterine adhesion (IUA). Previous studies have shown that postoperative oral estrogen or an intrauterine physical barrier could reduce the recurrence of IUA by promoting the proliferation of the endometrium or inhibiting the reformation of adhesions. Our team designed an intrauterine stent that can release estrogen within the uterine cavity slowly. In this study, we aimed to investigate the efficacy and safety of the estrogen-releasing intrauterine system in preventing the recurrence of moderate to severe IUA. METHODS: This was a multicenter prospective randomized controlled 2-arm parallel trial that included patients who were diagnosed with moderate to severe IUA and who received TCRA. A total of 250 patients were randomly assigned, at a 1:1 ratio, to receive the intrauterine estrogen-releasing system or a Foley catheter balloon combined with oral estrogen therapy after surgery. The primary outcome was the rate of adhesion reduction in the two groups. The secondary outcomes included endometrial thickness at the ovulation period, menstrual improvement rates, and other reported adverse events during follow-up. RESULTS: The average daily drug release amount for all the tested stents was 0.21 mg/day. At 60 days postoperatively, the rate of adhesion reduction was significantly greater in the experimental group than in the control group (93.33% vs. 58.56%, p < 0.001). The endometrium of the experimental group was thicker than that of the control group (p < 0.001). Consistently, the rate of improvement in menstruation was greater in the experimental group than in the control group (p = 0.010). No grade 3-4 adverse events were found in the two groups during the 1-year follow-up. CONCLUSIONS: In the cohort of patients with moderate to severe IUA, the intrauterine estrogen-releasing system was more effective at reducing adhesion than traditional oral estrogen combined with an intrauterine Foley catheter after TCRA. This novel intrauterine system provides a new option for the management of IUA after surgery. TRIAL REGISTRATION: The registration number is NCT04972032. Date of registration: August 15, 2021.

Thermosensitive hydrogel as a sustained release carrier for mesenchymal stem cell-derived extracellular vesicles in the treatment of intrauterine adhesion.

Intrauterine adhesion (IUA), a prevalent etiology of female infertility, is attributed to endometrial damage. However, conventional therapeutic interventions for IUA are plagued by high recurrence rates. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) demonstrate the promising therapeutic effects on IUA, but the current efficacy of extracellular vesicles (EVs) is hindered by lower retention and bioavailability. In this study, a thermosensitive hydrogel was utilized as a prolonged release carrier to improve the retention and bioavailability of hUCMSC-EVs in IUA treatment. The hydrogel-EVs complex effectively prolonged EVs retention in human endometrial stromal cells and an IUA mouse model. The complex exhibited superior protection against cellular injury, significantly alleviated endometrial damage, inhibited fibrosis, suppressed inflammation, and improved fertility compared to EVs alone. The results indicated that thermosensitive hydrogel enhanced the therapeutic capacity of EVs for IUA by prolonging their retention in the uterine environment. The hydrogel-EVs complex provides a novel strategy for the sustained release of hUCMSC-EVs in the treatment of IUA.

Evaluation of nasogastric tube fixation methods: adhesion, displacement and skin integrity.

OBJECTIVE: to evaluate three methods of nasogastric tube fixation in terms of adhesion, displacement and skin integrity. METHOD: ex vivo study, with a sample of 30 experimental noses (10 for each type of fixation), developed with porcine skin, based on the average measurements of the human nose, in which 14-gauge polyvinyl chloride probes were inserted and 2 methods of fixation with adhesive tape (Fixation A and B) and one with an industrial device (Fixation C) were used. Each group was exposed to traction of 50, 100 and 500g sequentially over 12 and 24 hours, testing: adhesion capacity, probe displacement and skin integrity. The Chi-square test of independence was calculated for nominal variables and Student's t-tests and analysis of variance (p< 0.05) for rational variables. RESULTS: fixation B showed lower adhesion capacity (p <0.001) when compared to the other two fixations. A mean displacement of 52.17 mm was observed in the probes fixed by methods A and B and a greater occurrence of lesions associated with fixations A and C (p = 0.001). CONCLUSION: the results show complications related to the fixations: lack of adhesion, displacement of the probe and skin lesions, drawing attention to the complexity of the procedure.

Visceral to subcutaneous fat area ratio predicts severe abdominal adhesions in definitive surgery for anastomotic fistula after small intestine resection.

Abdominal adhesions manifests following abdominal infections triggered by intestinal fistulas. The severity of such adhesions depends on the extent of fiber deposition and peritoneal fibrinolysis following peritoneal injury, which may be influenced by sustained inflammation within the abdominal cavity. In this regard, the visceral-to-subcutaneous fat area (VFA/SFA) ratio has been implicated as a potential marker of inflammation. This study aimed to explore the relationship between VFA/SFA and abdominal adhesions. This multicenter study was conducted across four tertiary institutions and involved patients who had undergone definitive surgery (DS) for intestinal fistula from January 2009 and October 2023. The presence of abdominal adhesions was determined intraoperatively. VFA/SFA was investigated as a potential risk factor for severe adhesions. The study comprised 414 patients with a median age of 50 [interquartile range (IQR) 35-66] years and a median body mass index of 20.0 (IQR 19.2-22.4) kg/m2, including 231 males with a median VFA/SFA of 1.0 (IQR 0.7-1.2) and 183 females a median VFA/SFA of 0.8 (0.6-1.1). VFA/SFA was associated with severe abdominal adhesions in males [odds ratio (OR) = 3.34, 95% CI 1.14-9.80, p = 0.03] and females (OR = 2.99, 95% CI 1.05-8.53, p = 0.04). J-shaped association between VFA/SFA ratio and severe adhesions was revealed in both sex. The increasing trend can be revealed when OR more than 0.8, and 0.6 in males and females respectively. Preoperative VFA/SFA demonstrates predictive value for statues of severe abdominal adhesions in DS for anastomotic fistula after small intestine resection.

[Development and safety study of a 3D printed middle turbinate splint]. / Razrabotka i issledovanie bezopasnosti splinta dlya srednei nosovoi rakoviny, izgotovlennogo s ispol'zovaniem 3D-pechati.

Adhesion of the middle turbinate to the lateral wall of the nasal cavity and synechia of the middle meatus are one of the common reasons for the failure of surgical interventions for chronic sinusitis. The use of specially shaped intranasal splints can solve the problem of preventing synechiae in the postoperative period. Many different devices and approaches have been proposed to prevent the development of this category of complications. This study proposes an anatomical version of the splint for the middle turbinate, developed using 3D computer modeling technologies followed by printing from a biocompatible elastic material on a Formlabs 3BL 3D printer. The shape and size of the splint were developed based on the analysis of computed tomography data of 50 adult patients. The safety of the developed device was studied in a group of 20 volunteers in whom the developed splint was installed on one side of the nasal cavity for 2 weeks after bilateral surgery. According to endoscopic examination and patient questionnaires, the developed splint did not cause local or systemic allergic reactions and did not create additional discomfort for the patient in the postoperative period. Installing a splint helped prevent the formation of synechiae. However, to determine clinical effectiveness, a study with a larger sample of patients is required.

Evaluation of sodium hyaluronate-based composite hydrogels for prevention of nasal adhesions.

During the healing process after intra-nasal surgery, the growth and repair of damaged tissues can result in the development of postoperative adhesions. Various techniques have been devised to minimize the occurrence of postoperative adhesions which include insertion of stents in the middle meatus, application of removable nasal packing, and utilizing biodegradable materials with antiadhesive properties. This study assesses the efficacy of two sodium hyaluronate (SH)-based freeze-dried hydrogel composites in preventing postoperative nasal adhesions, comparing them with commonly used biodegradable materials in nasal surgery. The freeze-dried hydrogels, sodium hyaluronate and collagen 1(SH-COL1) and sodium hyaluronate, carboxymethyl cellulose, and collagen 1 (SH-CMC-COL1), were evaluated for their ability to reduce bleeding time, promote wound healing, and minimize fibrous tissue formation. Results showed that SH-CMC-COL1 significantly reduced bleeding time compared to both biodegradable polyurethane foam and SH-COL1. Both SH-COL1 and SH-CMC-COL1 exhibited enhanced wound healing effects, as indicated by significantly greater wound size reduction after two weeks compared to the control. Histological analyses revealed significant differences in re-epithelialization and blood vessel count among all tested materials, suggesting variable initial wound tissue response. Although all treatment groups had more epithelial growth, with X-SCC having higher blood vessel count at 7 d post treatment, all treatment groups did not differ in all histomorphometric parameters by day 14. However, the long-term application of SH-COL1 demonstrated a notable advantage in reducing nasal adhesion formation compared to all other tested materials. This indicates the potential of SH-based hydrogels, particularly SH-COL1, in mitigating postoperative complications associated with nasal surgery. These findings underscore the versatility and efficacy of SH-based freeze-dried hydrogel composites for the management of short-term and long-term nasal bleeding with an anti-adhesion effect. Further research is warranted to optimize their clinical use, particularly in understanding the inflammatory factors influencing tissue adhesions and assessing material performance under conditions mimicking clinical settings. Such insights will be crucial for refining therapeutic approaches and optimizing biomaterial design, ultimately improving patient outcomes in nasal surgery.

Incidence of Intra-abdominal Adhesions Following Intraperitoneal Injection of Hemostatic Products in Rabbits.

INTRODUCTION: Definitive management of non-compressible intra-abdominal hemorrhage (NCIAH) currently requires a surgeon and operating room capable of performing damage control surgery. In a wartime scenario or a geographically remote environment, these may not be readily available. In this study, we sought to test the safety of 2 emerging injectable hemostatic agents (CounterFlow and Fast Onset Abdominal Management, or FOAM, poloxamer component) versus normal saline control over a prolonged monitoring duration following administration by a non-surgical provider. MATERIALS AND METHODS: The Institutional Animal Care and Use Committee approved all research conducted in this study. We randomized male New Zealand white rabbits into 2 monitoring cohorts of 24 hours and 2 weeks. Each cohort contained 3 treatment groups (n = 4 rabbits/group): CounterFlow, the testable poloxamer component of FOAM, and normal saline control. We injected each treatment intraperitoneally in the left lower abdominal quadrant. Doses were 15 mL/kg for CounterFlow, 6.3 mL/kg for the poloxamer component of FOAM, and 15 mL/kg for normal saline. We conducted all injections under isoflurane anesthesia monitored by trained veterinary staff. Animals were euthanized at each cohort end point, and a veterinary pathologist blinded to treatment type performed necropsy. The primary outcome was incidence of intra-abdominal adhesions at necropsy. Quantitatively, adhesions when present were graded by the veterinary pathologist on a 1 to 4 scale, where "1" represented adhesions involving from 1 to 25% of the examined abdomen, "2" represented from 26 to 50%, "3" represented from 51 to 75%, and "4" represented from 76 to 100%. Qualitatively, adhesions present were graded by degree ("1" = minimal, "2" = mild, "3" = moderate, and "4" = severe) and chronicity ("1" = acute, "2" = subacute, and "3" = chronic). We also drew d-dimer blood values and measured body weights for each animal. Statistical analysis included either repeated measures 2-way ANOVA or a mixed-effects model (in the case of missing data) with Geisser-Greenhouse correction. We adjusted multiple comparisons using Tukey statistical hypothesis tests. RESULTS: In the 2-week cohort, 3 CounterFlow animals showed adhesions judged to be "1" quantitatively. Qualitatively, 2 of these were assessed as "1" for degree of adhesions and the other demonstrated a "2." On the chronicity of adhesions scale, 1 animal demonstrated a "2" and 2 demonstrated a "3." No animals in other groups (FOAM and control) demonstrated adhesions. CounterFlow-treated animals showed a statistically significant rise in d-dimer values in the 24-hour cohort only. In the 2-week cohort, CounterFlow-treated animals showed a decrease in body weight at 24 hours after injection but returned to their baseline (normal) body weights at 7 days. CONCLUSIONS: Findings from this study demonstrate that the tested ingredients of FOAM poloxamer component are safe for intraperitoneal injection and hold potential for further study directed toward prehospital non-compressible intra-abdominal hemorrhage management by non-surgical providers. Although CounterFlow produced abdominal adhesions in 3 of 4 rabbits in the 2-week cohort, these were determined to be "minimal" or "mild" in degree.

The results of preventing postoperative achilles tendon adhesion using cross-linked and non-cross-linked hyaluronic acid, a study with rat model.

BACKGROUND: There are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries. PURPOSE: This study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair. METHODS: Twenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments. RESULTS: Non-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects. CONCLUSIONS: Non-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.

Interleukin-33 promotes intrauterine adhesion formation in mice through the mitogen-activated protein kinase signaling pathway.

IL-33 belongs to the inflammatory factor family and is closely associated with the inflammatory response. However, its role in the development of intrauterine adhesions (IUAs) remains unclear. In this study, the role of IL-33 in the formation of IUAs after endometrial injury was identified via RNA sequencing after mouse endometrial organoids were transplanted into an IUA mouse model. Major pathological changes in the mouse uterus, consistent with the expression of fibrotic markers, such as TGF-ß, were observed in response to treatment with IL-33. This finding may be attributed to activation of the phosphorylation of downstream MAPK signaling pathway components, which are activated by the release of IL-33 in macrophages. Our study provides a novel mechanism for elucidating IUA formation, suggesting a new therapeutic strategy for the prevention and clinical treatment of IUAs.

Establishment and evaluation of a stable and reliable rat model of peritoneal adhesions.

BACKGROUND: In this study, we aimed to establish a stable and standardized animal model of peritoneal adhesions. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided (n = 12 each) into blank control, classic cecum sidewall, ischemic button, and cecum-sidewall suture groups. The modified American Fertility Society adhesion score was used on postoperative day 7 to evaluate adhesions. Sixty male Sprague-Dawley rats were used to dynamically observe the adhesion characteristics of cecum-sidewall ischemic injury suture model at different time points (n = 60, randomly divided into groups a-e with 12 rats each). The modified American Fertility Society and Zühlke histologic scoring systems, hematoxylin-eosin staining, Masson staining, and computed tomography of the abdomen were used to evaluate adhesions on postoperative days 1, 3, 5, 7, and 14. RESULTS: No peritoneal adhesions were observed in the blank control group on postoperative day 7. In the classic cecum sidewall group, 8 rats had inconsistent adhesions, which had a modified American Fertility Society adhesion score of 2.25 ± 1.96. All rats in the ischemic button and cecum-sidewall suture groups developed significant adhesions with modified American Fertility Society scores of 3.08 ± 1.31 and 4.67 ± 0.78, respectively. When the modified American Fertility Society score was used, statistically significant differences were observed between the classic cecum sidewall groups and cecum-sidewall suture groups and between the ischemic button groups and cecum-sidewall suture groups. All animals in groups a-e developed adhesions; adhesion scores increased gradually with time. CONCLUSIONS: The cecum-sidewall ischemic injury suture model is a stable and standardized animal model of peritoneal adhesions.

Application of infrared thermography in assessing presence and severity of intra-abdominal adhesions.

Abdominal surgeries can sometimes lead to the formation of intra-abdominal adhesions, which may result in severe complications. Despite the availability of several diagnostic procedures, thermography has not been used for identifying intra-abdominal adhesions. Therefore, the objective of the current study was to assess abdominal temperature changes in rats with experimentally induced intra-abdominal adhesions. A total of 48 female rats were randomly divided into 4 groups (n = 12 each): Control (Group C), Laparotomy (Group Lap), Peritoneal Button Creation (Group PBC), and Uterus horn (Group UH). Skin temperature of abdominal region was measured before the procedure (T0) and daily thereafter until day 7 (T7). On day 7, all rats were euthanized for macroscopic evaluation, adhesion scoring, histopathological, immunohistochemical and immunofluorescence analyses. Significant differences were observed between Group C and Group PBC and Group UH at T5, while at T6 and T7, there was a difference between Group C and Group Lap, Group PBC, and Group UH in abdominal skin temperature (P < 0.05). The highest level of inflammation, angiogenesis, IL-1ß, and VEGF were observed in Group PBC followed by Group UH, Group Lap, and Group C (P < 0.05). There was a significant difference in adhesion formation between Group C and Groups Lap, PBC, and UH (P = 0.02). However, no significant difference was found in adhesion scores between Groups Lap, PBC, and UH (P = 0.25). A significant difference was found in mean abdominal skin temperature between adhesion scores 4 and 0, 1, and 2 (P < 0.05), while no significant difference was observed between adhesion scores 3 and 4 (P > 0.05). In conclusion, the current study suggests that the presence of intra-abdominal adhesions is associated with an increase in abdominal temperature, and this increase is correlates with the severity of adhesion.

CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion†.

Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-ß1 (TGF-ß1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-ß1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-ß1-induced fibrosis. CTRP6 markedly decreased TGF-ß1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.

Organism-Inspired Antioxidant Bioadhesive with Strong Sealing Ability to Prevent Epidural Adhesion.

Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.

Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L­serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L­serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L­serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L­serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.

Hepatocyte Growth Factor DNA Aptamer for Prevention of Postoperative Peritoneal Adhesion via Enhancement of Fibrinolysis and Inhibition of Mesothelial Mesenchymal Transition.

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.

Prolonged adhesiolysis to pregnancy interval is associated with placenta accreta spectrum in women with intrauterine adhesion.

BACKGROUND: Both the trauma of endometrium and hysteroscopic adhesiolysis can lead to a high rate of placenta accreta spectrum (PAS) in women with intrauterine adhesion (IUA). This study analysed the impact of time interval from adhesiolysis to pregnancy on PAS in IUA women. METHODS: Patients diagnosed with IUA who underwent adhesiolysis in Anhui Women and Children's Medical Centre between January 2016 and December 2020 were included in this case-series study. Clinical data were obtained from electronic medical records and telephone interviews. RESULTS: Among a total of 102 IUA women with successful pregnancies, 8 (7.8%) suffered from miscarriages with PAS, and 94 (92.2%), 47 with PAS and 47 without PAS, had successful delivery. The total prevalence of PAS in pregnant women with IUA was 53.9% (55/102). The average time from adhesiolysis to pregnancy in the PAS group was significantly longer than in the non-PAS group (14.2 ± 5.7 vs. 10.3 ± 4.4 months, p = 0.000). Regression analysis showed that AFS grade (OR = 7.40, 95% CI 1.38-39.73, p = 0.020) and adhesiolysis to pregnancy interval time between 12 and 24 months (OR = 12.09, 95% CI 3.76-38.83, p = 0.000) were closely related to PAS. A Kaplan-Meier analysis showed the median interval time to PAS was 16.00 months (95% CI 15.11-16.89). CONCLUSIONS: We assume that prolonged adhesiolysis to pregnancy interval may be considered a significant risk factor for PAS in IUA women.

Both the trauma of endometrium and hysteroscopic adhesiolysis can result in a high rate of placenta accreta spectrum in women with intrauterine adhesion. This study analysed the impact of time interval from adhesiolysis to pregnancy on placenta accreta spectrum in intrauterine adhesion women. This case-series study included patients diagnosed with intrauterine adhesion who underwent adhesiolysis in Anhui Women and Children's Medical Centre between January 2016 and December 2020. Clinical data were obtained from electronic medical records and telephone interviews. We assume that prolonged adhesiolysis to pregnancy interval may be considered a significant risk factor for placenta accreta spectrum in intrauterine adhesion women.

Evaluation of Interaction With Bio-absorbable Polyglycolic Acid Spacer and Anti-adhesive Agents Using a Rat Experimental Model.

BACKGROUND/AIM: Neskeep®, an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep® using rat models. MATERIALS AND METHODS: Animal experiments were performed using 60 rats, which underwent Neskeep® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm®, INTERCEED®, AdSpray®, and only Neskeep® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion. RESULTS: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep®, Seprafilm®, INTERCEED®, and AdSpray® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm® group on day 28. CONCLUSION: Seprafilm® may exhibit an anti-adhesive effect when used with Neskeep®.