Auto-crosslinked Hyaluronic Acid Gel Research Articles

Human umbilical cord-derived mesenchymal stem cells and auto-crosslinked hyaluronic acid gel complex for treatment of intrauterine adhesion.

The purpose of this study was to explore the therapeutic characteristics of mesenchymal stem cells generated from human umbilical cord (hUC-MSCs) when utilized in conjunction with auto-crosslinked hyaluronic acid gel (HA-gel) for the management of intrauterine adhesion (IUA). The goal was to see how this novel therapy could enhance healing and improve outcomes for IUA patients. In this study, models of intrauterine adhesion (IUA) were established in Sprague-Dawley (SD) rats, which were then organized and divided into hUC-MSCs groups. The groups involved: hUC-MSCs/HA-gel group, control group, and HA-gel group. Following treatment, the researchers examined the uterine cavities and performed detailed analyses of the endometrial tissues to determine the effectiveness of the interventions. The results indicated that in comparison with to the control group, both HA-gel, hUC-MSCs, and hUC-MSCs/HA-gel groups showed partial repair of IUA. However, in a more notable fashion transplantation of hUC-MSCs/HA-gel complex demonstrated significant dual repair effects. Significant outcomes were observed in the group treated with hUC-MSCs and HA-gel, they showed thicker endometrial layers, less fibrotic tissue, and a higher number of endometrial glands. This treatment strategy also resulted in a significant improvement in fertility restoration, indicating a profound therapeutic effect. The findings of this study suggest that both HA-gel, hUC-MSCs, and hUC-MSCs/HA-gel complexes have the potential for partial repair of IUA and fertility restoration caused by endometrium mechanical injury. Nonetheless, the transplantation of the hUC-MSCs/HA-gel complex displayed exceptional dual healing effects, combining effective anti-adhesive properties with endometrial regeneration stimuli.

Adhesion barriers in laparoscopic myomectomy: Evidence from randomized clinical trials.

To evaluate the effectiveness of different adhesion barriers in the prevention of de novo adhesion development after laparoscopic myomectomy. A systematic review was performed by searching seven electronic databases for all randomized clinical trials (RCTs) comparing the use of any absorbable adhesion barrier (i.e. intervention group) with either no treatment or placebo (i.e. control group) in the prevention of adhesion development after laparoscopic myomectomy. Eight RCTs with a total of 748 participants (392 in the intervention group and 356 in the control group) were included. The assessed adhesion barrier methods were: oxidized regenerated cellulose (ORC) in two studies, auto-crosslinked hyaluronic acid (HA) gel in two studies, 4% icodextrin solution in one study, modified HA and carboxy-methylcellulose in one study, polyethylene glycol ester trilysine amine solution plus a borate buffer solution in one study, and polyethylene glycol amine plus dextran aldehyde polymers in another study. Adhesion barrier methods showing the most promising results were: ORC, auto-crosslinked HA gel, and polyethylene glycol amine plus dextran aldehyde polymers.

Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials.

Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced development of intrauterine instruments, more intrauterine diseases can be successfully cured by hysteroscopic surgery. Among these, submucosal myoma is one of the best examples. Submucosal myomas are often related to abnormal bleeding, anemia, and possible infertility or miscarriage. However, submucosal myoma after hysteroscopic myomectomy may be complicated by IUA in various grades of severity, and its incidence and prevalence might be nearly one-quarter to one-third of patients, suggesting an urgent need for efforts to decrease the risk of developing IUA after hysteroscopic myomectomy. Many strategies have been reported to be useful for this purpose, and intrauterine application of anti-adhesive gels, such as polyethylene oxide–sodium carboxymethylcellulose (PEO-NaCMC) or auto-crosslinked hyaluronic acid (ACHA), has become increasingly popular in routine clinical practice. This meta-analysis is aimed at investigating the effect of ACHA on the primary prevention of IUA formation after hysteroscopic myomectomy. A pooled analysis of three studies (hysteroscopic surgeries for fibroids, polyps, and septum) including 242 women showed that using PEO-NaCMC or ACHA gel decreased the IUA rate with an odds ratio (OR) of 0.364 (95% confidence interval (CI) 0.189–0.703, p = 0.03). Pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction of the development of IUA postoperatively (OR 0.285, 95% CI 0.116–0.701, p = 0.006). All of this suggests that the use of ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA, although more evidence is needed.

Auto–Cross-Linked Hyaluronic Acid Gel for Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis: A Randomized Controlled Trial

To investigate auto-cross-linked hyaluronic acid gel for the prevention of intrauterine adhesion (IUA) recurrence after hysteroscopic adhesiolysis. A single-center, double-blinded randomized controlled trial. A tertiary university hospital. Two hundred seventy-two patients with moderate-to-severe (American Fertility Society [AFS] score ≥5) IUAs underwent hysteroscopic adhesiolysis. The patients were randomized to receive standard care along with auto-cross-linked hyaluronic acid gel after surgery (treatment group) or standard care only (control group). All patients had second-look hysteroscopy at 4 weeks and hormonal therapy for 2 cycles after surgery. Two hundred sixty patients were eligible and randomized; 245 patients successfully completed the study (n = 122 in treatment group, and n = 123 in control group). The primary outcome measure was IUA recurrence at second-look hysteroscopy. The secondary outcome measures included an improvement in the AFS score and menstrual pattern. There was no significant difference with regard to IUA recurrence (31.1% vs 39.8%) or median AFS score at second-look hysteroscopy (2, interquartile range [2-4] vs 2, interquartile range [2-4]) or improvement in the menstrual pattern at 3-month follow-up (87.7% vs 76.4%), in the treatment and control groups, respectively. The application of auto-cross-linked hyaluronic acid gel did not seem to improve IUA recurrence after hysteroscopic adhesiolysis.

In situ repair abilities of human umbilical cord-derived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with intrauterine adhesion.

Increasing occurrence of moderate to severe intrauterine adhesion (IUA) is seriously affecting the quality of human life. The aim of the study was to establish IUA models in nonhuman primates and to explore the dual repair effects of human umbilical cord-derived mesenchymal stem cells (huMSCs) loaded on autocrosslinked hyaluronic acid gel (HA-GEL) on endometrial damage and adhesion. Here, we recorded the menstrual cycle data in detail with uterine cavities observed and endometrial tissues detected after intervention, and the thicker endometria, decreased amount of fibrotic formation, increased number of endometrium glands, etc., suggested that both HA-GEL and huMSC/HA-GEL complexes could partially repair IUA caused by mechanical injury, but huMSC/HA-GEL complex transplantation had notable dual repair effects: a reliable antiadhesion property and the promotion of endometrial regeneration.

Comparison of Autocross-Linked Hyaluronic Acid Gel and Intrauterine Device for Preventing Intrauterine Adhesions in Infertile Patients: A Randomized Clinical Trial.

Objectives:The objective of this study is to evaluate the efficacy of autocross-linked hyaluronic acid (HA) compared with intrauterine device (IUD) for preventing intrauterine adhesions (IUAs) in infertile patients after hysteroscopic adhesiolysis.Materials and Methods:A randomized clinical trial (ChiCTR-IOR-16007746). Upon completion of adhesiolysis, 3 ml of HA gel was placed into the uterine cavity in Group A; 3 ml of HA gel and an IUD were placed in Group B; and only an IUD was placed in Group C. A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for the evaluation of IUA. The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society (AFS) scoring system.Results:Eighty-nine women were randomly distributed into two groups for intention to treat with 30 patients in Group A, 24 patients in Group B, and 35 patients in Group C. Patients were scored and stratified into three degrees and were enrolled using the simple random sampling method. The three groups were well balanced. There were no significant differences in age, endometrial thickness, the previous number of pregnancy, and the distribution of adhesion categories across mild, moderate, and severe between the three groups. The effective rate of IUA prevention, the AFS score after therapy, and the percentage improvements of Chinese score and AFS score before and after surgery were statistically significant difference between Groups A and C. The clinical pregnancy rate in Group A was higher than those in Groups B and C, but the difference was not statistically significant.Conclusion:HA gel has an advantage over an IUD in reducing IUA recurrence and decreasing adhesions.

[Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study].

To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid (HA) gel for preventing intrauterine adhesion (IUA) after hysteroscopic adhesiolysis. A prospective, randomized, double blinded and controlled clinical trial (level I) was performed. According to American Fertility Society (AFS) scoring system, 120 patients (treatment group: 60 cases, control group: 60 cases) with moderate to severe IUA were enrolled. Upon completion of adhesiolysis, a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group; patients in the control group, however, only received Foley balloon catheter. Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA. Primary endpoint was the reduction rate of IUA at 3 months after surgery. The secondary endpoints include total AFS score, score of each individual AFS category. At 3 months after surgery, auto-crosslinked HA gel resulted in significantly higher effective rate for reduction of adhesion, the effective rate were 76% (42/55) and 48% (27/56) respectively (P = 0.000 9); the total AFS score of treatment group was 2.1 ± 1.1, and significantly lower than that of control group (3.7 ± 2.5, P = 0.000 8). Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern (P = 0.037 8, P = 0.000 4). The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [13% (7/55) versus 38% (21/56), P = 0.000 6]. No adverse events and complications were observed. Auto-crosslinked HA gel coule be able to reduce IUA, decrease adhesion severity, and improve menopause postoperatively. This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures.

Role of morphologic characteristics of the uterine septum in the prediction and prevention of abnormal healing outcomes after hysteroscopic metroplasty.

STUDY QUESTIONCan morphologic measurements (width, length and surface area) of the uterine septum predict healing-dependent abnormal anatomic results [ARs; residual septum (RS) and intrauterine adhesions in other locations (IUA-OLs)] after complete hysteroscopic metroplasty (HM)?SUMMARY ANSWERSignificant predictors of ARs are the septal width and, to a lesser extent, septal surface area.WHAT IS KNOWN ALREADYAnatomic results after hysteroscopic metroplasty have very large variation. A RS >1 cm and IUA-OLs can aggravate reproductive outcomes, resulting in the need for reoperation. New criteria for diagnosing a uterine septum according to the European Society of Human Reproduction and Embryology (ESHRE) and European Society for Gynaecological Endoscopy (ESGE) have been suggested (ESHRE-ESGE criteria). Autocross-linked hyaluronic acid gel (autocross-linked polysaccharide) has an antiadhesive effect.STUDY DESIGN, SIZE, DURATIONA prospective, observational cohort study was performed with 96 women consecutively enrolled between 2007 and 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen who had uterine septum and previous miscarriage or infertility presented for evaluation at a university hospital, private hospital or private medical center were included. Preoperative septal width, length and surface area were determined with three-dimensional sonohysterography. Women were treated by hysteroscopy in a standardized manner with three- or four-dimensional transrectal ultrasound guidance (complete resection). Patients received either no adhesion barrier (49 patients) or adhesion barrier with autocross-linked polysaccharide (47 patients). Anatomic results were assessed with three-dimensional sonohysterography and second-look hysteroscopy. Healing-dependent ARs were reported using both American Society of Reproductive Medicine (ASRM) criterion of RS length >1 cm (ASRM>1 cm criterion) and ESHRE-ESGE criteria. Univariate and multivariate logistic regression were used to identify predictors of RS, IUA-OLs and ARs.MAIN RESULTS AND ROLE OF CHANCEIn patients who had no adhesion barrier, ARs were diagnosed in 11 of 49 patients (23%) using the ASRM > 1 cm criterion and in 20 of 49 patients (41%) using the ESHRE-ESGE criteria for RS [odds ratio (OR)ESHRE-ESGE:ASRM, 2.4, P = 0.05]. In the patients who had autocross-linked polysaccharide, ARsASRM > 1 cm were diagnosed in 2 of 47 patients (4%) and ARsESHRE-ESGE in 4 of 47 patients (9%). RSESHRE-ESGE was diagnosed significantly more often than RSASRM > 1 cm 19 of 96 (20%) versus 5 of 96 (5%) in all patients (ORESHRE-ESGE:ASRM > 1 cm = 4.5, P < 0.01). In patients who had no adhesion barrier, logistic regression with ASRM > 1 cm and ESHRE-ESGE criteria showed that the width and surface area were predictors of ARs. Models adjusted by patient group confirmed the significance of width as a predictor of ARsASRM > 1 cm [OR for width, 3.5 (P < 0.01); OR for group, 0.22 (P < 0.01)], width as a predictor of ARsESHRE-ESGE [OR for width, 2.2 (P < 0.01); OR for group, 0.26 (P < 0.01)] and surface area as a predictor of ARsASRM > 1 cm [OR for surface area, 1.5 (P < 0.01)]; OR for group, 0.32 (P < 0.01). In patients who had autocross-linked polysaccharide, these predictors were not significant. Receiver-operating characteristic curves showed cutoff values for ARsASRM > 1 cm (septal width, 3.42 cm; septal surface area, 4.68cm2) and ARsESHRE-ESGE (septal width, 3.42 cm; septal surface area, 3.51cm2).LIMITATIONS AND REASONS FOR CAUTIONPatients were enrolled in the adhesion barrier group in a time-dependent, consecutive and non-randomized manner.WIDER IMPLICATIONS OF THE FINDINGSA wide septum and large surface area may be indications for adhesion barrier. The use of autocross-linked polysaccharide reduces the risk of ARs. The ESHRE-ESGE criteria may cause greater frequency of recognition of RS than the ASRM > 1 cm criterion, which could result in more frequent reoperations with use of the ESHRE-ESGE criteria, possibly without any significant effect on reproductive performance.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by Jagiellonian University (grant no. K/ZDS/003821). The authors have no competing interest to declare.

Comparison of 4% icodextrin and auto-crosslinked hyaluronic acid gel in terms of efficacy and cost effectivity in preventing postoperative abdominal adhesions

This experimental study was designed to compare the effects and costs of 4% icodextrin and hyaluronic acid in intraabdominal adhesion formation in rats. This study included 30 healthy Wistar albino rats, each weighing 250-300 gr. Following cecal-ileal abrasion to rats in each group, the following treatments were applied: Group 1 (control, n:10) 5 ml saline irrigation; Group 2 (n:10) 5 ml 4% icodextrin solution; Group 3 (n:10) 3 ml auto-crosslinked hyaluronic acid gel. After 14 days, following a second operation, adhesion intensity scoring, histopathological assessment (inflammation, fibrosis) and costs were compared between groups. The lowest postoperative adhesion intensity score was found in the group 3 and the highest score was found in the group 1 (p=0.028). Group 3 had a non-significantly lower adhesion intensity score than group 2 (p>0.05). In terms of inflammation and fibrosis, group 2 had the lowest score, but there were no significant differences between all the groups (p>0.05). In terms of cost, 4% icodextrin is less expensive than hyaluronic acid. The results demonstrated that both hyaluronic acid and 4% icodextrin are similarly effective in reducing postoperative intraabdominal adhesions. In addition, 4% icodextrin is more cost-effective, which can be an advantage for clinical studies.

Reproductive outcome after autocrosslinked hyaluronic acid gel application in infertile patients who underwent laparoscopic myomectomy

Autocrosslinked hyaluronic acid gel is useful for preventing postsurgical adhesion formation in infertile patients who have undergone laparoscopic myomectomy, and it increases the pregnancy rate more than laparoscopic myomectomy alone. Moreover, pregnancy rate is significantly higher with the use of subserous sutures.

Reduction of neural adhesions by biodegradable autocrosslinked hyaluronic acid gel after injury of peripheral nerves: an experimental study.

Adhesion formation is a serious problem in peripheral nerve surgery, frequently causing dysfunction and pain. The authors aimed to develop an objective biomechanical method of quantifying nerve adhesions and to use this technique for the evaluation of the efficacy of an autocrosslinked hyaluronic acid (HA) gel as an antiadhesion therapy. Thirty-three female Wistar rats underwent dissection, crush injury, or transection plus repair of the sciatic nerve. The nerves were or were not treated with the HA gel. Six weeks after surgery, the adhesions formed were assessed by measuring the peak force required to break the adhesions over a standardized area. Results of biomechanical measurements demonstrated that the peak force significantly increased as the severity of the injury increased. After using the HA gel to treat the nerve, the peak force was significantly reduced in rats with any of the three types of injuries; peak force decreased by 26% in the animals in the dissection group, 29% in the crush injury group, and 38% in the transection and repair group, compared with the untreated animals. The biomechanical method described is an objective, quantitative technique for the assessment of nerve adherence to surrounding tissue. It will be a valuable tool in future studies on antiadhesion therapies. Furthermore, HA gel significantly reduces nerve adhesions after different types of nerve injuries.

Reproductive outcome after auto-crosslinked hyaluronic acid gel application in infertile patients who underwent laparoscopic myomectomy

Reproductive outcome after auto-crosslinked hyaluronic acid gel application in infertile patients who underwent laparoscopic myomectomy

Effectiveness of autocrosslinked hyaluronic acid gel after laparoscopic myomectomy in infertile patients: a prospective, randomized, controlled study

Objective To assess the efficacy of autocrosslinked hyaluronic gel in postsurgical adhesion prevention after laparoscopic myomectomy. Design Prospective, randomized, controlled study. Setting University of Naples “Federico II”. Patient(s) Thirty-six infertile women with symptomatic myomas were randomly divided into two groups of 18 patients each. Intervention(s) Laparoscopic myomectomy with subserous sutures or interrupted figure 8 sutures, with (group A) or without (group B) application of autocrosslinked hyaluronic acid (HA) gel. Main outcome measure(s) Rate of postsurgical adhesions at 60–90 days of follow-up. Result(s) The rate of subjects who developed postoperative adhesions was significantly lower in group A in comparison with group B (27.8% vs. 77.8%). In both groups, the rate of adhesions was significantly higher in patients treated with interrupted figure 8 sutures than with subserous sutures. Conclusion(s) Autocrosslinked HA gel is a promising resorbable agent barrier for the reduction of postoperative adhesions after laparoscopic myomectomy. Moreover, the type of suture is a factor influencing the postsurgical adhesion formation.