Auto-crosslinked Hyaluronic Acid Research Articles

Evaluation of the Filling Effects and Safety of an Injectable Gel Based on A Multi-Crosslinked Hyaluronan (Mu.C.H) Technology for the Correction of Facial Ageing Defects

Background: Hyaluronic acid (HA) plays a crucial role in skin health: it moisturizes, supports connective tissue and supports collagen production. With increasing age, HA levels decrease leading to wrinkles and a loss of facial volume. Hyal System DUO, an HA-based filler, addresses these defects through a unique combination of auto-crosslinked HA and BDDE-crosslinked HA. Purpose: To evaluate the safety, tolerability, and long-term performance of the HA-based filler in correcting facial wrinkles and restoring volume, turgor and elasticity to the skin. Materials and Methods: In a single-center observational study, 27 subjects were examined who were treated with the HA-based dermal filler in various areas of the face. Performance was assessed at six visits using the Wrinkle Severity Rating Scale (WSRS), the Facial Volume Loss Scale (FVLS), and the Global Aesthetic Improvement Scale (GAIS). Safety was monitored by recording adverse events. Results: The HA-based filler showed significant and sustained performance in reducing wrinkles and restoring facial volume over the entire study period. Subject satisfaction was consistently high, with self-reported improvements consistent with physician’s assessments. Adverse events were mild and transient, demonstrating the safety of the product. The cross-linking technologies in this HA-based filler contributed to its lasting effect, providing a natural improvement for facial rejuvenation.

Evaluation of the Filling Effects and Safety of an Injectable Gel Based on A Multi-Crosslinked Hyaluronan (Mu.C.H) Technology for the Correction of Facial Ageing Defects

Background: Hyaluronic acid (HA) plays a crucial role in skin health: it moisturizes, supports connective tissue and supports collagen production. With increasing age, HA levels decrease leading to wrinkles and a loss of facial volume. Hyal System DUO, an HA-based filler, addresses these defects through a unique combination of auto-crosslinked HA and BDDE-crosslinked HA. Purpose: To evaluate the safety, tolerability, and long-term performance of the HA-based filler in correcting facial wrinkles and restoring volume, turgor and elasticity to the skin. Materials and Methods: In a single-center observational study, 27 subjects were examined who were treated with the HA-based dermal filler in various areas of the face. Performance was assessed at six visits using the Wrinkle Severity Rating Scale (WSRS), the Facial Volume Loss Scale (FVLS), and the Global Aesthetic Improvement Scale (GAIS). Safety was monitored by recording adverse events.

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.

Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner

BackgroundDeclining ovarian function in advance-aged women and in premature ovarian insufficiency (POI) patients seriously affects quality of life, and there is currently no effective treatment to rescue ovarian function in clinic. Stem cell transplantation is a promising therapeutic strategy for ovarian aging, but its clinical application is limited due to the low efficiency and unclear mechanism. Here, a novel combination of umbilical cord-mesenchymal stem cells (UC-MSCs) and autocrosslinked hyaluronic acid (HA) gel is explored to rescue ovarian reserve and fecundity in POI and naturally aging mice.MethodsTo investigate HA prolonged the survival after UC-MSCs transplantation, PCR and immunofluorescence were performed to track the cells on day 1, 3, 7 and 14 after transplantation. The effects of HA on UC-MSCs were analyzed by CCK8 assay, RNA-sequencing and 440 cytokine array. In vivo experiments were conducted to evaluate the therapeutic effects of UC-MSCs combined with HA transplantation in 4-vinylcyclohexene diepoxide (VCD)-induced POI mice and naturally aging mice model. Ovarian function was analyzed by ovarian morphology, follicle counts, estrous cycle, hormone levels and fertility ability. To investigate the mechanisms of stem cell therapy, conditioned medium was collected from UC-MSCs and fibroblast. Both in vitro ovarian culture model and 440 cytokine array were applied to assess the paracrine effect and determine the underlying mechanism. Hepatocyte growth factor (HGF) was identified as an effective factor and verified by HGF cytokine/neutralization antibody supplementation into ovarian culture system.ResultsHA not only prolongs the retention of UC-MSCs in the ovary, but also boosts their secretory function, and UC-MSCs promote follicular survival by activating the PI3K-AKT pathway through a paracrine mechanism both in vitro and in vivo. More importantly, HGF is identified as the key functional cytokine secreted by MSCs.ConclusionsThe results show that HA is an excellent cell scaffold to improve the treatment efficiency of UC-MSCs for ovarian aging under both physiological and pathological conditions, and the therapeutic mechanism is through activation of the PI3K-AKT pathway via HGF. These findings will facilitate the clinical application of MSCs transplantation for ovarian disorders.

Autocross-linked hyaluronic acid gel and adipose-derived mesenchymal stem cell composites for the treatment intrauterine adhesions

ObjectiveTo evaluate the effect of adding adipose-derived mesenchymal stem cells (ASCs) to autocross-linked hyaluronic acid (HA) gel for intrauterine adhesion (IUA) treatment. MethodsA rat IUA model was established by mechanical curettage and infection, and then different treatments were administered to the rats on day 7 after modeling. Ninety-six rats were randomly divided into the following groups: IUA model group, gel therapy group, and combination therapy group (HA gel combined with ASCs). Eight rats per group were sacrificed on days 7, 10, 14 and 21 for the subsequent experiments. Morphological changes were determined by hematoxylin-eosin staining and Masson staining. Smad3 and leukocyte inhibitory factor (LIF) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. ResultsThe endometrial lines in the gel therapy group and the combination therapy group were more complete than those in the model group. Masson staining showed that fibrosis area rates in the gel therapy group and the combination therapy group were significantly lower than those in the model group on day 7(P < 0.05). During the observation period, the fibrosis area rates in the combination therapy group remained lower than those in the model group (P < 0.05). The mRNA expression of Smad3 in the combination therapy group was lower than that in the model group and gel therapy group during the observation period (P < 0.05). The mRNA expression level of LIF in the combination therapy group was higher than that in the model group and the gel therapy group throughout the observation period (P < 0.05). ConclusionsHA gel was effective in preventing the IUA adhesion formation at the early stage of the observation period, while ASC enhanced this effect throughout the observation period. Gel and ASC composites helped to improve endometrial receptivity.

O-138 Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial

Abstract Study question Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&amp;C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs. Summary answer Reproductive outcomes in women with identified and treated IUAs following recurrent D&amp;C for miscarriage are impaired compared to women without IUAs. What is known already The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&amp;C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance. Study design, size, duration This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&amp;C for miscarriage. All included women received a diagnostic hysteroscopy 8–12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization. Participants/materials, setting, methods Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&amp;C, were randomized for D&amp;C alone or D&amp;C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded. Main results and the role of chance In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value &amp;lt;0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups. Limitations, reasons for caution In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol. Wider implications of the findings As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&amp;C in women with a miscarriage. In case D&amp;C is necessary, application of ACP gel should be considered. Trial registration number Netherlands Trial Register NTR 3120.

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.

Association of Platelet-Rich Plasma and Auto-Crosslinked Hyaluronic Acid Microparticles: Approach for Orthopedic Application.

Platelet-rich plasma (PRP) associated with high molecular weight hyaluronic acid (HA) has been clinically used for tissue regeneration in orthopedics. Despite the recognized beneficial clinical outcomes (e.g., early pain control, improvement of patients’ functional limitation and longer-term effectiveness compared to PRP and HA alone in mild and moderate osteoarthritis treatments), its use is still challenging and controversial due to lack of standardization of association practical protocols. Moreover, most studies neglect the matrix structure, that generates the ultimate properties of the association among platelets, fibrin network and the microparticles. In the present work, we aimed to analyze the influence of the PRP/HA association with a controlled matrix structure on the stability, rheological behavior, release of growth factors and in vitro proliferation of human adipose-derived mesenchymal cells (h-AdMSCs). The attenuation of the negative charge of HA was also evaluated. Pure PRP (P-PRP) (i.e., plasma enriched with platelets and poor in leukocytes) was prepared by centrifugation and activated with serum and calcium chloride (AP-PRP). Autocrosslinked hyaluronic acid (AHA) was prepared by organocatalyzed auto-esterification and structured in microparticles (MPAHA) by shearing. The attenuation of the negative charge of MPAHA was performed with chitosan (CHT) by polyelectrolyte complexation yielding MPAHA-CHT. The results showed that microparticles (MPs) have viscoelastic properties, extrusion force and swelling ratio appropriate for injectable applications. The association of AP-PRP with the controlled structure of MPAHA and MPAHA-CHT formed a matrix composed of platelets and of a fibrin network with fibers around 160 nm located preferably on the surface of the MPs with an average diameter of 250 μm. Moreover, AP-PRP/MPAHA and AP-PRP/MPAHA-CHT associations were non-toxic and supported controlled growth factor (PDGF-AB and TGF-β1) release and in vitro proliferation of h-AdMSC with a similar pattern to that of AP-PRP alone. The best h-AdMSC proliferation was obtained with the AP-PRP/MPAHA-CHT75:25 indicating that the charge attenuation improved the cell proliferation. Thus, the association of AP-PRP with the controlled structure of HA can be a valuable approach for orthopedic applications.

Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial

To examine whether intrauterine application of auto-crosslinked hyaluronic acid (ACP) gel, after dilatation and curettage (D&C), reduces the incidence of intrauterine adhesions (IUAs). Multicenter; women and assessors blinded prospective randomized trial. University and university-affiliated teaching hospitals. A total of 152 women with a miscarriage of <14weeks with at least one previous D&C for miscarriage or termination of pregnancy. Women were randomly assigned to either D&C plus ACP gel (intervention group) or D&C alone (control group). A follow-up diagnostic hysteroscopy was scheduled 8-12weeks after the D&C procedure. The primary outcome was the number of women with IUAs and the secondary outcome was the severity of IUAs. Outcomes were available for 149 women: 77 in the intervention group and 72 in the control group. The IUAs were observed in 10 (13.0%) and 22 women (30.6%), respectively (relative risk, 0.43; 95% confidence interval 0.22-0.83). Mean adhesion score and the amount of moderate-to-severe IUAs were significantly lower in the intervention group according to the American Fertility Society (AFS) and European Society of Gynecological Endoscopy classifications systems of adhesions. Intrauterine application of ACP gel after D&C for miscarriage in women with at least one previous D&C seems to reduce the incidence and severity of IUAs but does not eliminate the process of adhesion formation completely. Future studies are needed to confirm our findings and to evaluate the effect of ACP gel on fertility and reproductive outcomes. NTR3120.

Sterilization of auto-crosslinked hyaluronic acid scaffolds structured in microparticles and sponges.

This work evaluated the effects of UV irradiation, plasma radiation, steam and 70% ethanol treatments on the sterilization and integrity of auto-crosslinked hyaluronic acid (HA-ACP) scaffolds structured in microparticles and sponges aiming in vivo applications for regenerative medicine of bone tissue. The integrity of the microparticles was characterized by rheological behavior, while for the sponges, it was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. The effectiveness of the sterilization treatment was verified by the number of microorganism colonies in the samples after the treatments. In conclusion, plasma radiation was the best treatment for the sponges, while steam sterilization in the autoclave at 126°C (1.5kgf/cm2) for 5min was the best treatment for the microparticles.

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.

Auto‐crosslinked hyaluronic acid gel accelerates healing of rabbit flexor tendons in vivo

This study's purpose was to assess the in vivo effect of auto-crosslinked hyaluronic acid (HA) gel, a natural HA derivative with increased viscosity and tissue residence time, on adhesions and healing of injured and surgically repaired rabbit digital flexor tendons. The second and third right deep digital flexor tendons from 48 rabbits (n = 96 tendons) were cut and repaired with a modified Kessler and running peripheral suture. Animals were randomized to two groups, receiving either HA gel or saline injected around both freshly repaired tendons. After 2, 3, 6, and 12 weeks, six rabbits in each group were euthanized. Tendon pull-out force and breaking strength were measured as a value for adhesion formation and tendon healing, respectively. A histological assessment of adhesions and healing was related to the mechanical results. A significantly faster increase in breaking strength was found in HA gel-treated compared to saline-treated tendons; this coincided with a significantly accelerated tissue repair response after injury. No significant difference in adhesion formation was found between the two groups at any time. Our results indicate a significant acceleration of in vivo healing of tendons treated with HA gel. Adhesion formation was unaffected. These results could have important clinical value in promoting rehabilitation after tendon injury.

Adhesion prevention in gynecologic surgery

The purpose of this review is to discuss new substances and techniques to prevent post-surgical adhesion formation. Intraperitoneal administration of sprayable hydrogel and hyaluronic acid appears to decrease postmyomectomy adhesions. Intrauterine instillation of auto-crosslinked hyaluronic acid is associated with fewer intrauterine adhesions. Temporary abdominal oophoropexy after surgery of stage III and IV endometriosis might be beneficial in reducing ovarian adhesion. There has been a wide range of adhesion-reducing substances evaluated in animal models. However, in clinical situations, no adhesion-preventing substance, material, or barrier is unequivocally effective. In view of surgical technique, compared to laparotomy, the laparoscopic approach is associated with less adhesion formation. Temporary abdominal oophoropexy may provide a promising technique to prevent ovarian adhesions. Future research should also be directed toward preventing intrauterine adhesions.

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.