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Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-β1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-β1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-β1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-β1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-β1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. The Toll-like receptor 4 (TLR4) signaling pathway is one of the most common inflammation-related pathways, and it has been demonstrated that TLR4 is highly expressed in adhesive tissues; however, the function of TLR4 in adhesion formation has not yet been studied. In the present study, the expression of TLR4 was first detected by immunohistochemical (IHC) and double-immunofluorescence staining in 40 mice, which were randomly divided into four groups, and sacrificed at 1, 3, 5 and 7 days after surgery. Subsequently, another 40 mice were randomly divided into five groups; with the exception of the sham group, the other groups were modeled and treated with saline that contained DMSO, sodium hyaluronate (HA), TAK-242 or TAK-242 + HA (applied to damaged peritoneal wounds). A total of 7 days after surgery, the mice were sacrificed and specimens were collected. Inflammation was detected by hematoxylin and eosin staining, and ELISA of transforming growth factor- β1 (TGF-β1) and interleukin-6 (IL-6); collagen deposition was examined by Masson staining and IHC staining of α-SMA; and reactive oxygen species (ROS) were detected by ROS staining and malondialdehyde (MDA) assay. The results revealed that TLR4 was highly expressed in the adhesive tissues at 3, 5 and 7 days after surgery. In addition, TAK-242 + HA treatment could reduce abdominal adhesion formation, exhibiting lower Nair's score and inflammation scores, lower TGF-β1 and IL-6 levels, and lower collagen thickness and α-SMA levels compared with those in the control group. In addition, the TAK-242 + HA group had lower levels of ROS and MDA compared with those in the control group. The present study revealed that TLR4 was highly expressed in the process of adhesion formation and its inhibitor, TAK-242, combined with HA, could reduce adhesion formation by reducing inflammation and ROS, and alleviating collagen deposition., (© 2024. The Author(s).)

Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)-dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. STATEMENT OF SIGNIFICANCE: Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m 3 ; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m 2 of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the in vivo adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation. STATEMENT OF SIGNIFICANCE: Despite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Abnormal autophagy and the transforming growth factor-β (TGFβ)-SMAD3/7 signaling pathway play an important role in the development of intrauterine adhesions (IUAs); however, the exact underlying mechanisms remain unclear. In this study, we used IUA patient tissue and SMAD7 conditional knockout mice to detect whether SMAD7 effected IUA via regulation of autophagy and the TGFβ-SMAD3 signaling pathway. We applied a combination of techniques for the detection of p-SMAD3, SMAD7, autophagy and fibrosis-related proteins, autophagic flux, and analysis of the SMAD3 binding site. Endometrial tissue of patients with IUA exhibited lower expression levels of SMAD7. In endometrial stromal cells, silencing of SMAD7 inhibited autophagic flux, whereas overexpressed SMAD7 promoted autophagic flux. This SMAD7-mediated autophagic flux regulates the stromal-myofibroblast transition, and these phenotypes were regulated by the TGFβ-SMAD3 signaling pathway. SMAD3 directly binds to the 3'-untranslated region of transcription factor EB (TFEB) and inhibits its transcription. SMAD7 promoted autophagic flux by inhibiting SMAD3, thereby promoting the expression of TFEB. In SMAD7 conditional knockout mice, the endometria showed a fibrotic phenotype. Simultaneously, autophagic flux was inhibited. On administering the autophagy activator rapamycin, this endometrial fibrosis phenotype was partially reversed. The loss of SMAD7 promotes endometrial fibrosis by inhibiting autophagic flux via the TGFβ-SMAD3 pathway. Therefore, this study reveals a potential therapeutic target for IUA., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intrauterine adhesion (IUA), also referred to as Asherman's syndrome, is characterized by fibrosis, inflammation, and can cause amenorrhea and infertility due to abnormal endometrial healing. Histological and Molecular methods were used to evaluate the efficacy of EPO, which is traditionally known for its anti-inflammatory and fibrinolytic properties, in preventing the formation of IUA. Oral administration of EPO reduced the formation of adhesion bands and promoted endometrial regeneration. EPO administration decreased extracellular matrix accumulation, evidenced by the down-regulation of tissue COL1A1 and COL3A1 expression. The anti-inflammatory effect of EPO was confirmed by a reduction in oxidants and down-regulation of pro-inflammatory cytokines including TNF-α, IL-6, IFN-γ, and IL-1β. Furthermore, EPO improved embryonic development parameters, including size and weight of embryo, as well as increased embryo count and live embryo percentage in the rat IUA model. EPO also positively enhanced implantation markers, particularly enlargement and mass gain in the placenta of the treated group, consequently improving pregnancy outcomes such as the number of babies, percent of live babies, baby weight and gestation time. Histopathological investigation provides evidence that oral administration of EPO showed no toxicity on the main three organs including liver, kidney and heart. These results showed that EPO can be considered as a safe and natural product with potent anti-inflammatory and fibrinolytic properties without any observed side effects for the treatment of IUA., (© 2024. The Author(s).)

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-β, 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., (© 2024. The Author(s).)

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/m 2 , 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., (© 2024. The Author(s).)

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 L‑serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L‑serine 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 L‑serine 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 L‑serine 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde (CHO). Further, the double crosslinked AHBC/PSC hydrogel was successfully fabricated between AHBC and PSC via forming dynamic covalent acylhydrazone bonds and borate ester bonds. Results showed that AHBC/PSC hydrogel had in situ gelation behavior, satisfactory mechanical properties (storage modulus of about 1 kPa and loss factor Tan δ of about 0.5), suitable wet tissue adhesion strength of about 2.3 kPa on rat abdominal wall, and good biocompatibility, achieving an ideal physical barrier. Particularly, CGA could be responsively released from the hydrogel by breakage of borate ester bonds between CGA and PBA based on high reactive oxygen species (ROS) levels of damaged tissue and exhibited great ROS scavenging capability to regulate inflammation and promote the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the grafted SB as a zwitterionic group could reduce protein adsorption and fibroblast adhesion. Finally, the in vivo experiments revealed that AHBC/PSC hydrogel with good safety and in vivo retention behavior of about 2 weeks, effectively prevented PAA by regulating the inflammatory microenvironment and alleviating the fibrosis process. In brief, the versatile AHBC/PSC hydrogel would provide a more convenient and efficient approach for PAA prevention. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesion (PAA) widely occurs after surgery and is often accompanied by severe complications. Excessive inflammation and oxidative stress are very crucial for PAA formation. This study provides a ROS-responsive and scavenging hydrogel with suitable mechanical properties, good biocompatibility and biodegradability, and resistance to protein and fibroblast. The antioxidant and anti-inflammatory active ingredient could be responsively released from the hydrogel via triggering by the high ROS levels in the postoperative microenvironment thereby regulating the inflammatory balance. Finally, the hydrogel would effectively regulate the development process of PAA thereby achieving non-adhesion wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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 ® ., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments., Competing Interests: The authors declare no conflicts of interest.

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.

Background: Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA., Methods: Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-β1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection., Results: qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC., Conclusions: Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objectives: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model., Materials and Methods: Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15 th (early period) or 30 th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15 th and 30 th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation., Results: Histopathologically, there were no significant differences among the groups on the 15 th day. However, on the 30 th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05)., Conclusion: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

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., (Creative Commons Attribution license.)

Mesenchymal stem cells play important roles in repairing injured endometrium. However, the molecular targets and potential mechanism of the endometrial recipient cells for stem cell therapy in intrauterine adhesion (IUA) are poorly understood. In this study, umbilical cord mesenchymal stem-cell-conditioned medium (UCMSCs-CM) produced positive effects on a Transforming growth factor beta (TGF-β) induced IUA cell model. RNA-sequencing was performed on clinical IUA tissues, and the top 40 upregulated and top 20 downregulated mRNAs were selected and verified using high-throughput (HT) qPCR in both tissues and cell models. Based on a bioinformatic analysis of RNA-sequencing and HT-qPCR results, 11 mRNAs were uncovered to be the intervention targets of UCMSCs-CM on IUA endometrium cell models. Among them, IGFBP3 was striking as a key pathogenic gene and a potential diagnostic marker of IUA, which exhibited the area under the curve (AUC), sensitivity, specificity were 0.924, 93.1% and 80.6%, respectively in 60 endometrial tissues. The silencing of IGFBP3 exerted positive effects on the IUA cell model through partially upregulating MMP1 and KLF2. In conclusion, RNA-sequencing combined with HT qPCR based on clinical tissues and IUA cell models were used in IUA research and our results may provide some scientific ideas for the diagnosis and treatment of IUA., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Endometrial damage resulting from surgical procedures is a significant cause of intrauterine adhesion, thin endometrium, and subsequent miscarriage and infertility. Unfortunately, there is currently no effective clinical solution to promote endometrial regeneration after severe injury. In this study, we combined fibrinogen (Fg) and P(LLA-CL) by electrostatic spinning to form a stable nano-biomaterial Fg/P(LLA-CL), which can promote endometrial regeneration. After inducing physical injury to rat endometrium, we found that Fg/P(LLA-CL) membranes placed in the uterine cavities increased endometrial thickness and the number of glands after injury, while reducing the area of endometrial fibrosis. In addition, Fg/P(LLA-CL) increased neovascularization and decreased COL1A1 deposition. The expression of TGF-β1, a cytokine that promotes fibrosis, was down-regulated in the early stage of injury. Finally, fertility assays confirmed that Fg/P(LLA-CL) improved the pregnancy rate in rats with endometrial injury, and its safety was verified by blood tests and pathological examination of heart, liver, spleen, lung, and kidney. Therefore, Fg/P(LLA-CL) shows great potential as a safe and nontoxic biomaterial for endometrial regeneration, ultimately improving pregnancy outcomes in patients with intrauterine adhesion., (© 2023 Wiley Periodicals LLC.)

The potential role of metabolic reprogramming in fibrogenesis has recently attracted interest. Extracellular matrix stiffness, inflammation, and subsequent oxidative stress are essential mediators in the causation of fibrosis. The prevention of post-surgical adhesion is a challenge in medicine. It is defined as a fibrotic disorder in which adhesive bands develop after abdominal or pelvic surgery. Despite many studies related to the pathogenesis of post-surgical adhesion (PSA), many unknowns exist. Therefore, evaluating different pathways may help characterize and identify the cause of fibrotic scar formation post-operation. Glucose and lipid metabolism are crucial metabolic pathways in the cell's energy production that may be targeted by hypoxia-induced factor alpha and profibrotic cytokines such as TGF-β to mediate fibrogenesis. Inhibition of upregulated metabolic pathways may be a viable strategy for ameliorating post-surgical adhesion. In this review, we have discussed the potential role of altered glucose and lipid metabolism in extracellular matrix (ECM) stiffness and oxidative stress as crucial mediators in fibrosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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-β receptor inhibitor (TGF-βRi)-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-βRi. 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., (© 2023 Wiley-VCH GmbH.)

Background: Intrauterine adhesion (IUA) caused by endometrial mechanical injury has been found as a substantial risk factor for female infertility (e.g., induced abortion). Estrogen is a classic drug for the repair of endometrial injury, but its action mechanism in the clinical application of endometrial fibrosis is still unclear., Objective: To explore the specific action mechanism of estrogen treatment on IUA., Methods: The IUA model in vivo and the isolated endometrial stromal cells (ESCs) model in vitro were built. Then CCK8 assay, Real-Time PCR, Western Blot and Dual- Luciferase Reporter Gene assay were applied to determine the targeting action of estrogen on ESCs., Results: It was found that 17β-estradiol inhibited fibrosis of ESCs by down-regulating miR-21-5p level and activating PPARα signaling. Mechanistically, miR-21-5p significantly reduced the inhibitory effect of 17β-estradiol on fibrotic ESCs (ESCs-F) and its maker protein (e.g., α-SMA, collagen I, and fibronectin), where targeting to PPARα 3'- UTR and blocked its activation and transcription, thus lowering expressions of fatty acid oxidation (FAO) associated key enzyme, provoking fatty accumulation and reactive oxygen species (ROS) production, resulting in endometrial fibrosis. Nevertheless, the PPARα agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F, which is consistent with the efficacy of estrogen intervention., Conclusion: In brief, the above findings revealed that the miR-21-5p/PPARα signal axis played an important role in the fibrosis of endometrial mechanical injury and suggested that estrogen might be a promising agent for its progression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To surgically demonstrate preconceptional laparoscopic repair of a chronic myometrial defect with mesh reinforcement, resulting in a successful pregnancy outcome., Design: Video case report. The Institutional Ethical Committee was consulted, and the requirement for approval was waived because the video describes a modified surgical technique. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, and others), and other applicable sites., Setting: A referral advanced gynecological endoscopy center., Patient: A 27-year-old woman (P 0 A 1 ) was diagnosed with myomas during pregnancy, resulting in miscarriage at 22 weeks. Laparotomy and myomectomy were performed 2 months later, and three 8-cm myomas were removed. The endometrial cavity opened posteriorly during surgery, and retained products of conceptions were removed. Periconceptional imaging done after two years showed few intramural myomas and a deficient myometrium in the posterior fundal region. Laparoscopy revealed a defect in the posterior fundal aspect of the uterus with leakage of dye, which was converted to laparotomy and myomectomy with the repair of the myometrial defect. After 1 year, follow-up magnetic resonance imaging showed thinned-out posterior myometrium with a focal area of absent myometrium in the midline and endometrial prolapse. The patient was advised on surrogacy, but she wanted to repair the defect again and try for pregnancy, so she was referred to our center. With the background of a few case reports using mesh to reinforce myometrial repair (1, 2), we counseled the patient about the myometrial repair with the additional use of mesh as an off-label use., Intervention: The risk of uterine rupture after myomectomy is rare (<1%) (3), but it is a severe complication. High-risk cases, like significant myometrial defects or previous ruptures, may require surgical correction. Native repair may not achieve optimal results in all cases. Alternative approaches, like the additional use of mesh or biological materials, have been reported (4). In this case, we demonstrate the use of dual mesh for scar repair. Synthetic mesh over the uterus is used in laparoscopic procedures like sacrohysteropexy and cerclage. We used Parietex (Covidien, New Haven, CT, USA) mesh, a composite macroporous polyester mesh usually used for ventral hernia repair. It has an outer hydrophilic, absorbable collagen barrier that reduces adhesion formation. Laparoscopically, after adhesiolysis, a significant defect was demonstrated on the posterior wall of the uterus (Fig. 1). A complete resection of the fibrotic tissue along the edges of the scar defect was done to expose healthy myometrium. Myometrium was repaired in two layers, excluding the endometrium, with a V-Loc (Covidien, Dublin, Ireland) No. 1-0 suture. Parietex mesh was sutured over the repaired posterior myometrium to reinforce it (Fig. 2)., Main Outcome Measures: The postoperative myometrial thickness on imaging and pregnancy outcome., Results: Postoperative ultrasound scan after 6 weeks demonstrated restoration of posterior wall myometrial thickness of 14 mm. The patient was conceived through in vitro fertilization techniques 4 months after surgery. Antenatal follow-up was uneventful except for suspicion of posterior placenta accreta. She underwent an elective cesarean section with uterine artery embolization at 34 weeks and delivered a healthy infant weighing 1,950 g. Placental removal was uneventful. On inspection, the posterior surface of the uterus was intact without dehiscence, meshing in situ with minimal adhesions (Fig. 3)., Conclusion: Myometrial scar defects can cause potential obstetric complications. Native repair of scar defects may not achieve optimal results, as in our case. Mesh repair of myomectomy scar defects can be used as an alternative approach, as exemplified in this case. However, further studies are required to establish the safety and efficacy of this approach., Competing Interests: Declaration of interests P.G.P. has nothing to disclose. N.J. has nothing to disclose. M. Shah has nothing to disclose. M. Sudhakar has nothing to disclose. G.P. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Intrauterine adhesion (IUA), a major cause of uterine infertility, is pathologically characterized by endometrial fibrosis. Current treatments for IUA have poor efficacy with high recurrence rate, and restoring uterine functions is difficult. We aimed to determine the therapeutic efficacy of photobiomodulation (PBM) therapy on IUA and elucidate its underlying mechanisms. A rat IUA model was established via mechanical injury, and PBM was applied intrauterinely. The uterine structure and function were evaluated using ultrasonography, histology, and fertility tests. PBM therapy induced a thicker, more intact, and less fibrotic endometrium. PBM also partly recovered endometrial receptivity and fertility in IUA rats. A cellular fibrosis model was then established with human endometrial stromal cells (ESCs) cultured in the presence of TGF-β1. PBM alleviated TGF-β1-induced fibrosis and triggered cAMP/PKA/CREB signaling in ESCs. Pretreatment with the inhibitors targeting this pathway weakened PBM's protective efficacy in the IUA rats and ESCs. Therefore, we conclude that PBM improved endometrial fibrosis and fertility via activating cAMP/PKA/CREB signaling in IUA uterus. This study sheds more lights on the efficacy of PBM as a potential treatment for IUA., (© 2023 American Society for Photobiology.)

Aim: To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery., Materials and Methods: A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results., Results: In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan., Limitations: There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided., Conclusion: This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Hydrogel-based wound dressings have been developed for rapid wound healing; however, their adhesive properties have not been adequately investigated. Excessive adhesion to the skin causes wound expansion and pain when hydrogels absorb exudates and swell at wound sites. Herein, we developed a low-adhesion and low-swelling hydrogel dressing using alginate, which is non-adhesive to cells and skin tissue, CaCO 3 , and carbonated water. The alginate/CaCO 3 solution rapidly formed a hydrogel upon the addition of carbonated water, and the CO 2 in the hydrogel diffused into the atmosphere, preventing acidification and obtaining a pH value suitable for wound healing. Remarkably, the skin adhesion and swelling of the hydrogel were 11.9- to 16.5-fold and 1.9-fold lower, respectively, than those of clinical low-adhesion hydrogel dressings. In vivo wound-healing tests in mice demonstrated its therapeutic efficacy, and the prepared hydrogel prevented temporary wound dilation during early healing. These results illustrate the importance of controlling skin adhesion and swelling in wound dressings and demonstrate the potential clinical applications of this wound-friendly hydrogel dressing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Traumatic injuries may result in the formation of soft tissue adhesions between peripheral nerves and surrounding soft tissue. These soft tissue adhesions lead to compression and ischemic stress within fascicles due to nonpliability of adhered scar tissue, and nerve tension due to loss of nerve gliding from scar tethering. These changes in the soft tissue bed surrounding the nerve may result in axon degeneration and neuroma-in-continuity. Preclinical models that simulate clinically relevant levels of scar in the nerve environment may be impactful to the development of surgical techniques and treatments to prevent adhesions. This study presents the results of a rodent model with an induced indirect nerve injury by (1) thermal insult to the soft tissue bed surrounding the nerve and (2) air-drying the surrounding soft tissue bed of the nerve. Our findings suggest that inducing an injury of the soft tissue bed results in increased intraneural scar and extraneural adhesions to the nerve compared to a sham procedure. Thermal induced injuries showed more macrophages and changes in nerve health compared to air-dried induced injuries. The changes in the nerves of the induced injury groups, specifically the thermal injury group, may be meaningful for evaluating treatments for nontransected nerve injuries.

Intrauterine adhesions (IUA), characterized by endometrial fibrosis, is a challenging clinical issue in reproductive medicine. We previously demonstrated that epithelial-mesenchymal transition (EMT) and fibrosis of endometrial stromal cells (HESCs) played a vital role in the development of IUA, but the precise pathogenesis remains elucidated. Ferroptosis has now been recognized as a unique form of oxidative cell death, but whether it is involved in endometrial fibrosis remains unknown. In the present study, we performed an RNA-seq of the endometria from 4 severe IUA patients and 4 normal controls. Enrichment analysis and protein-protein interactions (PPIs) network analysis of differentially expressed genes (DEGs) were conducted. Immunohistochemistry was used to assess ferroptosis levels and cellular localization. The potential role of ferroptosis for IUA was investigated by in vitro and in vivo experiments. Here, we demonstrated that ferroptosis load is increased in IUA endometria. In vitro experiments showed that erastin-induced ferroptosis promoted EMT and fibrosis in endometrial epithelial cells (P < 0.05), but did not lead to pro-fibrotic differentiation in endometrial stromal cells (HESCs). Cell co-culture experiments showed that erastin-stimulated epithelial cell supernatants promoted fibrosis in HESCs (P < 0.05). In vivo experiments suggested that elevation of ferroptosis level in mice by erastin led to mild endometrial EMT and fibrosis. Meanwhile, the ferroptosis inhibitor Fer-1 significantly ameliorated endometrial fibrosis in a dual-injury IUA murine model. Overall, our findings revealed that ferroptosis may serve as a potential therapeutic target for endometrial fibrosis in IUA., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tendon adhesion is the most common outcome of tendon or tendon-to-bone healing after injury. Our group developed a hydrogel-nanoparticle sustained-release system previously to inhibit cyclooxygenases (COXs) expression and consequently prevent tendon adhesion and achieved satisfactory results. However, effective treatment of multiple tendon adhesions is always a challenge in research on the prevention of tendon adhesion. In the present study, an M2M@PLGA/COX-siRNA delivery system is successfully constructed using the cell membranes of M2 macrophages and poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Targeting properties and therapeutic effects are observed in mice or rat models of flexor digitorum longus (FDL) tendon injury combined with rotator cuff injury. The results showed that the M2M@PLGA/COX-siRNA delivery system has low toxicity and remarkable targeting properties to the injured areas. Treatment with the M2M@PLGA/COX-siRNA delivery system reduced the inflammatory reaction and significantly improved tendon adhesion in both the FDL tendon and rotator cuff tissues. These findings indicate that the M2M@PLGA delivery system can provide an effective biological strategy for preventing multiple tendon adhesions., (© 2023 Wiley-VCH GmbH.)

Purpose: The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods., Methods: A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm 2 ), group B (excision area: 2.0 × 0.25 cm 2 ), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome., Results: The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05)., Conclusion: Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFβ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFβ/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA., (© 2023 Wiley-VCH GmbH.)

Good endometrium is the prerequisite and guarantee for reproduction and maternal and child health. Endometrial injury caused by operation or non-operation can lead to menstrual irregularities, amenorrhea, abortion, infertility, and other gynecological diseases to bother women. Intrauterine adhesions (IUA) and thin endometrium are common diseases caused by abnormal repair after endometrium damage. The incidence of IUA is not low after uterine operative surgery, and the recurrence is pretty high after uterine adhesiolysis. At present, there were many methods for endometrial repair in clinic or in the laboratory, but the efficacy was different from methods to methods. They are mainly including estrogen therapy, stem cell therapy, complementary medicine therapy, and some physical barrier therapy. In order to guide the effective repair and regeneration of endometrium in clinic, this paper reviews the merit and demerit of these methods for endometrium regeneration and repair that have been proved to be effective in experiments and clinical in recent years., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Intrauterine adhesion (IUA), a leading cause of uterine infertility, is characterized by endometrial fibrosis. Implementing an appropriate animal model is essential for the research on the mechanisms of IUA. In the present study, we established and evaluated different intrauterine adhesion modeling procedures in rats to provide a reference for researchers. Rat IUA models were established by mechanical injury, 95% ethanol injection, and dual (mechanical injury with infection) injury. After two estrus cycles, the female rats were mated with sexually mature male rats, and uterine tissues were obtained on the 5th day of pregnancy. Hematoxylin and eosin staining and immunohistochemical detection of cytokeratin 19 and vimentin were performed to assess the morphology of the endometrium. Masson's trichrome staining and the expression of transforming growth factor-β1 and collagen I were used to assess the endometrium fibrosis. The expression of integrin avβ3, leukemia inhibitory factor, and homeobox gene A10 in the rat endometrium was used to evaluate the endometrial receptivity. In addition, the efficiency of embryo implantation was examined in the uterus on the 8th day of pregnancy. Our study found that mechanical injury caused by a curette can be completely repaired after two estrus cycles. However, dual injury and 95% ethanol injection can be used to establish an IUA rat model, and the dual injury is closer to the clinicpathological characteristics of IUA.

Peritoneal adhesions, a common postoperative complication of laparotomy, are still treated with physical barriers, but their efficacy and ease of use are controversial. In this paper, we developed a wound microenvironment-responsive hydrogel composed of Antheraea pernyi silk protein (ASF) from wild cocoons and tyramine-modified hyaluronic acid (HA-Ph) loaded with azithromycin (AZI), glucose oxidase (GOX), and horseradish peroxidase (HRP). In addition, GOX-catalyzed oxygen production enhanced the antibacterial ability of the hydrogel. Moreover, the drug-loaded hydrogel increased macrophage CD206 expression while decreasing IL-6 and TNF-α expression. More importantly, the retarding effect of this novel hydrogel system on AZI almost eliminated the appearance of postoperative adhesions in rats. It was also found that the novel hydrogel enhanced the modulation of the TLR-4/Myd88/NF-κB pathway and TGF-β/Smad2/3 pathway by azithromycin in the locally damaged peritoneum of rats, which accelerated the remodeling of damaged tissues and dramatically reduced the deposition of collagen. Therefore, spraying the novel drug-loaded hydrogel on postoperative abdominal wounds can effectively inhibit the formation of postoperative adhesions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Intrauterine adhesion (IUA) is one of the principal causes of secondary infertility in women of reproductive age, which seriously affects female reproductive function and quality of life. In recent years, the incidence of IUA has been increasing year by year, but its pathological mechanism has not yet been clarified. This study intended to reveal the pathogenesis of IUA and find new therapeutic targets by analyzing the proteomic differences between intrauterine adhesion tissues and normal human endometrial tissues. In the label-free quantitative proteomics, we identified 789 up-regulated differentially expressed proteins (DEPs) and 539 down-regulated DEPs. These DEPs were further analyzed by Gene Ontology (GO) annotation and enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis to preliminarily clarify the biomarkers involved in the pathogenesis of the IUA. The DEPs were further verified by parallel reaction monitoring (PRM) to confirm the results of proteomics. Finally, 7 target proteins may be candidates for treatment and elucidating the pathophysiology of IUA. SIGNIFICANCE: IUA is a fertility complication, which has increasing incidence recently. Until now, only a little research paid attention to the proteomic changes of IUA. This is the first study focused on the comparative analysis of endometrial tissue between IUA patients and normal women. We found 7 key proteins that may become the potential biomarkers of IUA., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell-derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome-based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients., (© The Author(s) 2023. Published by Oxford University Press.)

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, antioxidation, anti-inflammation, and anti-cell adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin-3-gallate (EGCG) and hyaluronic acid (HA)-based microgels and poly(vinyl alcohol) (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including antioxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model was implemented to investigate the efficacy of our microgel-based hydrogels in preventing postoperative abdominal adhesions. The hydrogels, with a high molecular weight HA, significantly decreased the inflammation, oxidative stress, and fibrosis and reduced the abdominal adhesion formation, compared to the commercial Seprafilm group or Injury-only group. Label-free quantitative proteomics analysis demonstrated that S100A8 and S100A9 expressions were associated with adhesion formation; the microgel-containing hydrogels inhibited these expressions. The microgel-containing hydrogels with multifunctionality decreased the formation of postoperative intra-abdominal adhesions in a murine model, demonstrating promise for clinical applications.

Introduction: Postoperative peritoneal adhesions formed after abdominal surgery still continue to exist as an unresolved health problem., Aim: The aim of the present study is to examine whether omega -3 fish oil has a preventive effect on postoperative peritoneal adhesions., Methods: Twenty-one female Wistar-Albino rats were separated into 3 groups (sham, control, and experimental group), each consisting of 7 rats. In sham group, only laparotomy was performed. Both in control and experimental group rats; the right parietal peritoneum and cecum were traumatized to form petechiae. Following this procedure, unlike the control group, the abdomen was irrigated with omega-3 fish oil in the experimental group. Rats were re-explored on the 14th postoperative day and adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis., Results: None of the omega-3 fish oil given rats developed macroscopically postoperative peritoneal adhesion (P=0.005). Omega-3 fish oil formed an anti-adhesive lipid barrier on injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in control group rats while foreign body reactions were common in omega-3 given rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in omega-3 given rats than in control rats. (P=0.004)., Conclusion: Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.

The ability of animal cells to sense, adhere to and remodel their local extracellular matrix (ECM) is central to control of cell shape, mechanical responsiveness, motility and signalling, and hence to development, tissue formation, wound healing and the immune response. Cell-ECM interactions occur at various specialized, multi-protein adhesion complexes that serve to physically link the ECM to the cytoskeleton and the intracellular signalling apparatus. This occurs predominantly via clustered transmembrane receptors of the integrin family. Here we review how the interplay of mechanical forces, biochemical signalling and molecular self-organization determines the composition, organization, mechanosensitivity and dynamics of these adhesions. Progress in the identification of core multi-protein modules within the adhesions and characterization of rearrangements of their components in response to force, together with advanced imaging approaches, has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions. Perturbations of adhesion contribute to a broad range of diseases and to age-related dysfunction, thus an improved understanding of their molecular nature may facilitate therapeutic intervention in these conditions., (© 2022. Springer Nature Limited.)

Iatrogenic injury to endometrial tissue is the main cause of intrauterine adhesions (IUA) and infection can also damage the endometrium. The microbiota plays an important role in the health of the female reproductive tract. However, the mechanism is still unclear. In total, 908 patients with IUA and 11,389 healthy individuals were retrospectively selected for this clinical study. Participant information including vaginal microecological results and human papillomavirus (HPV) status were collected. Univariate and multivariate logistic regression analyses were used to identify the factors related to IUA. Next, animal experiments were performed in a curettage-induced IUA rat model. After the procedure, rats in the experimental group received a vaginal infusion of a Candida albicans (C. albicans) fungal solution. On days 3, 7, and 14 after curettage and infusion, the expression levels of IL-6, fibrotic pathway-related factors (TGF-β1, Smad 2, and COL1), and estrogen receptor (ER) and progesterone receptor (PR) in rat endometrial tissues were assessed. Fungal infection of the reproductive tract was found to be an independent risk factor for IUA (P < 0.05). The inflammatory response and degree of fibrosis were greater in rats infected with C. albicans than in the controls. The levels of IL-6, TGF-β1, Smad 2, and COL1 expression in endometrial tissues were significantly higher in the experimental group than in the control group (P < 0.05). However, the ER and PR levels were lower in the IUA group than in the non-IUA group (P < 0.05). C. albicans infection may be related to IUA. C. albicans elicits a strong inflammatory response that can lead to more severe endometrial fibrosis., (© 2023. The Author(s).)

Introduction: Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil., Methods: Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed., Results: Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups., Conclusion: Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model., Competing Interests: Declaration of competing interest The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of the study was to analyze histological changes in the site of the meshes FTOREX, FTOREX coated with carboxymethylcellulose, Ventralight ST, Symbotex, REPEREN-16-2 and decellularized porcine peritoneum on the parietal peritoneum of the pig., Material and Methods: At laparoscopy, 6 different meshes were placed intraperitoneally in each of the 3 pigs. After 90 days, the animals were taken out of the experiment. After staining with hematoxylin and eosin, quantitative morphometry and counting the number of vessels and cells in the interstitium in the areas of the mesh and peritoneum were performed. An immunohistochemical study with an antibody to pancytokeratins assessed the state of the initial peritoneum and neoperitoneum., Results: According to morphological characteristics, the meshes were divided into 3 groups: 1) with fluoropolymer coating FTOREX, 2) Ventralight ST and Symbotex, 3) REPEREN and decellularized peritoneum. In group 1, the surface area of the mesh threads was optimal in terms of the arrangement and arrangement of the threads relative to each other. This contributed to the formation of a relatively dense fibrous framework and a place to preserve the underlying peritoneum involved in the formation of the neoperitoneum. Despite the smallest surface area of the threads, in group 3, the greatest fibroblastic reaction was noted. Inflammatory changes were the least pronounced in group 1. They were the greatest in group 3, where there was a pronounced leukocyte reaction, combined with the processes of metaplasia, the development of fibrinoid necrosis, and the progression of the secondary inflammatory process. In group 1, the optimal ratio of newly formed vessels was noted, in group 2 - veins prevailed over arteries, in group 3 - the number of vessels was minimal. Immunohistochemical study showed that in group 1, mesothelial cells covered almost the entire surface of the implant, and there were also areas of preserved basic peritoneum. In group 2, mesothelium also covered most of the surface of the meshes, but the underlying peritoneum was absent. In group 3, on the contrary, a significant number of extended areas not covered with mesothelium were revealed., Conclusion: The conducted morphological and morphometric study showed that the most balanced ratio of the components of the newly formed fibrous tissue and blood vessels is observed when using implants with a fluoropolymer coating FTOREX. At the same time, the remaining basic peritoneum actively participated in the formation of the neoperitoneum. The Ventralight ST and Symbotex meshes also contributed to the formation of a full-fledged fibrous tissue and adequate vascular proliferation, however, they prevented the preservation of the underlying peritoneum, which practically excluded its participation in the formation of the neoperitoneum. The REPEREN mesh and decellularized porcine peritoneum led to the least balanced cell and vascular proliferation and the greatest fibroplastic reaction, which could further negatively affect the state of the formed scar.

Introduction: Human umbilical cord mesenchymal stem cells (UCMSCs) play an important role in repairing the damaged endometrium of intrauterine adhesion (IUA). Meanwhile, exosomes released by UCMSCs can mediate intercellular communication by delivering miRNAs. It has been shown that miR-543 level was reduced in IUA tissues. However, the role of miR-543 in the progression of IUA remains largely unknown. Therefore, we investigated the role of UCMSCs-derived exosomal miR-543 in IUA., Methods: In this study, human endometrial epithelial cells (hEECs) were treated with TGF-β1 for mimicking endometrial fibrosis in vitro. In addition, the IUA-like mouse model in vivo was established by a dual damage method of curettage and LPS infection., Results: The level of miR-543 was markedly reduced in hEECs exposed to TGF-β1 and in endometrium tissues of IUA mice. Additionally, miR-543 could be transferred from UCMSCs to hEECs via exosomes. Meanwhile, exosomal miR-543-derived from UCMSCs significantly reduced the expressions of N-cadherin, α-SMA, fibronectin 1 and elevated the expression of E-cadherin in TGF-β1-treated hEECs. Furthermore, UCMSCs-derived exosomal miR-543 attenuated IUA-induced endometrial fibrosis in vivo, as shown by the decreased N-cadherin, α-SMA and fibronectin 1 protein expressions., Discussion: Collectively, UCMSCs-derived exosomal miR-543 was able to prevent endometrial fibrosis both in vitro and in vivo via downregulating N-cadherin. These results may provide an insight into the clinical treatment for IUA., Competing Interests: Declaration of competing interest The authors declare there is no competing financial interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Intrauterine adhesion (IUA), resulting from pregnancy or nonpregnant uterine trauma, is one of the major causes of abnormal menstruation, infertility, or repeated pregnancy loss. Although a few methods, including hysteroscopy and hormone therapy, are routinely used for its diagnosis and treatment, they cannot restore tissue regeneration. Stem cells, which have self-renewal and tissue regeneration abilities, have been proposed as a promising therapy for patients with severe IUAs. In this review, we summarize the origin and features of endometrium-associated stem cells and their applications in the treatment of IUAs based on animal models and human clinical trials. We expect that this information will help to elucidate the underlying mechanism for tissue regeneration and to improve the design of stem cell-based therapies for IUAs.

Purpose: Endometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC., Methods: In this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate., Results: The eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p < .05). No intra- and postoperative complications were registered., Conclusion: This clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis., (© 2022. The Author(s).)

Although different products have been developed to prevent post-surgical adhesion, their efficacy remains unsatisfactory. This study aimed to evaluate the efficacy of the gelatin sponge in the prevention of post-surgical intra-abdominal adhesions in a rat model. Rats were randomly divided into sham, adhesion, and gelatin groups. All rats, except the sham group, underwent cecal abrasion to establish an adhesion model. After celiotomy, a sterile gelatin sponge was applied intra-abdominal on the abraded cecum in the gelatin group. Rats were sacrificed on day 14 post-surgery and intra-abdominal adhesions were evaluated and scored. Adhesion tissues were evaluated by histological, histochemical, and immunohistochemical analysis. Intra-abdominal adhesions were recorded in all rats of the adhesion group. Intra-abdominal application of gelatin sponge significantly (P < 0.001) reduced intra-abdominal adhesions by 91% in the gelatin group relative to the adhesion group. The histological analysis revealed a marked decrease (P < 0.001) in the inflammatory score and neovascularization in the gelatin group. The histochemical analysis found that gelatin sponge administration reduced adhesion formation and thickness of adhesion tissue. Moreover, gelatin sponge significantly (P < 0.0001) increased MMP-9 expression and decreased macrophage marker expression in adhesive tissue. This study revealed that the application of gelatin sponge markedly reduced the post-surgical intra-abdominal adhesions and suggests new guidance for using gelatin sponge as an anti-adhesive substance in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Intrauterine adhesion (IUA) is a condition caused due to damage or infection of the endometrium. It is characterized by continuous inflammation and following fibrosis and dysfunction. However, the current animal IUA models have several disadvantages, including complex operation, high mortality, and many extra distractions owing to opening of the abdominal cavity to expose the uterus. Mesenchymal stem cells (MSCs), which have been used in treatment of IUA, are heterogeneous and immunosuppressive. However, their therapeutic effect is not as good as expected., Methods: Here, we successfully built a new murine IUA model, called electric tool-scratching IUA model, and applied it in our experiments to investigate the efficacy of tumor necrosis factor-α (TNF-α) primed MSCs (T-MSCs). In the new model, we used a self-made electric tool that can cause mechanical damage to the endometrium without opening the abdominal cavity. ELISA and histological staining analysis were performed to evaluate pathological features of IUA. qRT-PCR, flow cytometry and immunofluoresence staining were performed to detect the phenotypes of macrophages. TMT proteomics quantification and western blotting assay were performed to analyze the differentially expressed proteins of MSC exosomes., Results: Based on the new IUA model, we found TNF-α pretreatment could enhance the ability of MSCs to relieve inflammation and reduce endometrium fibrosis. Mechanistically, T-MSC promoted macrophage polarization to M2 phenotype through exosomes. Subsequently, we found the expression of Galectin-1 was increased in T-MSC exosomes. Finally, we analyzed the gene expression pattern of Galectin-1 treated macrophages and found Galectin-1 promoted macrophage polarization to M2 phenotype mainly through the Jak-STAT signaling pathway., Conclusions: Our studies proposed an innovative mouse model and a better MSC treatment strategy for IUA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Pan, Yang, Wang, Jiang, Dou and Hou.)