Cross-linked Hyaluronic Acid Gel Research Articles

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

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

Microbiological Effects of Sodium Hypochlorite/-Amino Acids and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment.

To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis.

Histological evaluation of nonsurgical periodontal treatment with and without the use of sodium hypochlorite / amino acids and cross-linked hyaluronic acid gels in dogs

ObjectivesTo evaluate periodontal wound healing following scaling and root planing (SRP) in conjunction with the application of sodium hypochlorite/amino acids and cross-linked hyaluronic acid (xHyA) gels in dogs.Materials and MethodsIn four beagle dogs, 2-wall intrabony defects were created and metal strips were placed around the teeth. Clinical parameters were measured 4 weeks after plaque accumulation. The experimental root surfaces were subjected to SRP with either the subgingival application of a sodium hypochlorite/amino acid gel and a xHyA gel (test group) or SRP alone (control group) using a split-mouth design. Clinical parameters were re-evaluated at 6 weeks. The animals were sacrificed at 8 weeks for histological analysis.ResultsThe test group showed significant improvements in all clinical parameters compared to the control group. Histologically, the test group exhibited statistically significantly greater new bone formation [i.e., length of newly formed bone, new bone area] compared with the control group (p < 0.05). Furthermore, statistically significantly greater formation of new attachment [i.e., linear length of new cementum adjacently to newly formed bone with inserting collagen fibers] and new cementum was detected in the test group compared with the control group at 8 weeks (p < 0.05 and p < 0.01, respectively).ConclusionThe adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA gels to SRP offers an innovative novel approach to enhance periodontal wound healing/regeneration.Clinical relevanceThe present findings have for the first-time shown histologic evidence for periodontal regeneration in support of this novel treatment modality.

Long-Term Follow-Up of the Behavior of Facial Volumizing Cross-Linked Hyaluronic Acid Gels

Introduction: We present the long-term follow-up photographic and MRI data on 4 patients 42-44 months after cross-linked Hyaluronic Acid (HA) gel injection into the temple region. All injected HA gels were produced using the registered and patented “Inter Penetration Network Like®” (IPN-Like® cross-linking technology) (LABORATOIRES VIVACY, France). The initial results following injection and up to 24 months were previously reported [1,2]. Material and methods: Our study population comprised 4 Caucasian patients who were enrolled into our two previous studies that compared Stylage XL versus Stylage XL-Lido (incorporating lidocaine added at manufacturing) [1] and Stylage XL versus Stylage XXL [2]. Patients, radiologists and the independent evaluators were blinded to the type of product used. The 4 patients were each injected in both temporal fossae using the 2 different HA gels being compared (one on either side). All patients had their follow-up at month 42 after injection (M42) with the exception of one patent who her MRI and photographs taken at the same setting on month 44 (M44). Photographic assessments were undertaken by the injector and 2 independent experts using Merz-Analogic Scale® (MAS®) and the Global Aesthetic Improvement Scale (GAIS). Results: Except for participant 2 (Stylage® XL vs. Stylage® XL-Lido) on the Stylage® XL-Lido side, all the other participants were considered to have a degree of persisting improvement compared to baseline, according to experts scoring of photographs on MAS and GAIS, However, there was a gradual deterioration in the level of improvement compared to the other assessment time-points. MRI: Although the bolus of injected gel was spherical at D0, we observed a change in the shape of the implant over time on MRI, where it changed from a round to a “teardrop” shape. Slow resorption occurred from 18 months onwards. At M42-44, the gel appearance on MRI remained similar to that previously reported at M18. The MRI residual volume calculation showed persistent increased volume compared to the volume initially injected. The product location appeared stable. There were no radiological or clinical signs of inflammatory reaction in tissues adjacent to the gel. Conclusion: At long-term follow-up 42-44 months after initial injection there was still an improvement in the aesthetic appearance of the temporal fossa and the MRI images show the continued presence of the gel. We also noticed that Stylage®XL (without lidocaine) seemed to absorb more water than its counterpart with lidocaine. Likewise, Stylage® XL seemed to absorb more water than Stylage® XXL.

Clinical evaluation of sodium hypochlorite/amino acids and cross-linked hyaluronic acid adjunctive to non-surgical periodontal treatment: a randomized controlled clinical trial

ObjectivesTo compare the clinical outcomes obtained with either mechanical subgingival debridement in conjunction with a sodium hypochlorite and amino acids containing gel followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with mechanical debridement alone.Materials and MethodsFourty-eight patients diagnosed with stages II-III (Grades A/B) generalised periodontitis were randomly treated with either scaling and root planing (SRP) (control) or SRP plus adjunctive sodium hypochlorite/amino acid and xHyA gels (test). The primary outcome variable was reduction of probing depth (PD), while changes in clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were secondary outcomes. The outcomes were assessed at baseline, at 3 and 6 months following therapy.ResultsAll patients completed the 6 months evaluation. At 6 months, the test group showed statistically significantly better results in terms of mean PD reduction (2.9 ± 0.4 vs 1.8 ± 0.6 mm, p < 0.001). Similarly, mean CAL gain was statistically higher in the test group compared to the control one (test: 2.6 ± 0.5 vs control: 1.6 ± 0.6 mm, p < 0.001). Mean BOP decreased from 81.8 ± 16.2% to 48.9 ± 14.5% in control (p < 0.001) and from 83.2 ± 15.5% to 17.6 ± 11.5% in test (p < 0.001) groups with a statistically significant difference favouring the test group (p < 0.001). Mean PI scores were reduced statistically significantly in both groups (from 38.8 ± 26% to 26.5 ± 20.5% in control (p = 0.039) and from 60.6 ± 10.9% to 12.7 ± 8.9% in test group (p < 0.001)), with a statistically significant difference between the groups (p < 0.001). The number of moderate pockets (4–6 mm) were reduced from 1518 (41.2%) to 803 (22.6%) in the control and from 1803 (48.6%) to 234 (7.7%) in the test group with a statistically significant difference between the groups (p < 0.001), while the number of deep pockets (≥ 7 mm) changed from 277 (7.6%) to 35 (1.0%) in the control and from 298 (8.7%) to 4 (0.1%) in test group (p = 0.003).ConclusionWithin their limits the present data indicate that: a) both treatments resulted in statistically significant improvements in all evaluated clinical parameters, and b) the adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA to SRP yielded statistically significantly higher improvements compared to SRP alone.Clinical relevanceThe combination of sodium hypochlorite/amino acid and xHyA gels to subgingival mechanical debridement appears to represent a valuable approach to additionally improve the outcomes of non-surgical periodontal treatment.Clinical Trial Registration Number NCT04662216 (ClinicalTrials.gov).

Clinical Evaluation of a Novel Combination of Sodium Hypochlorite/Amino Acid and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment: A Case Series.

The adjunctive subgingival application of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid gels (high molecular weight) has been recently proposed as a novel modality to enhance the outcomes of non-surgical periodontal therapy. The aim of this prospective case series was to evaluate the clinical outcomes obtained following the subgingival application of a combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) gels in conjunction with non-surgical periodontal therapy. Twenty-one systemically healthy, non-smoking patients diagnosed with stage II-III, grade A/B periodontitis underwent full-mouth subgingival debridement (SD) performed with ultrasonic and hand instruments. All sites with probing depths (PD) ≥ 4 mm were treated with additional repeated (i.e., 2-3 times) instillation of sodium hypochlorite/amino acid gel in the periodontal pockets prior to and during SRP. Following mechanical debridement, a mixture of natural and cross-linked hyaluronic acid (high molecular) gel was applied in the pockets. The primary outcome variable was PD reduction; changes in clinical attachment level (CAL) and bleeding on probing (BOP) were the secondary outcomes. The clinical parameters were assessed at baseline, 3 and 6 months after therapy. Compared to baseline, a statistically significant mean reduction of PD values was obtained after 3 and 6 months, amounting to 2.6 ± 0.4 mm, and 2.9 ± 0.4 mm, respectively (p < 0.001). Mean CAL gain measured 2.3 ± 0.5 mm at 3 months and 2.6 ± 0.5 mm at 6 months in comparison to baseline (p < 0.001). Mean reduction of BOP values was 54.9 ± 16.9 % at 3 months and 65.6 ± 16.4 % at 6 months (p < 0.001). The number of moderate pockets (4-5 mm) decreased from 1808 at baseline to 274 at the 6-month evaluation, and the number of deep (≥ 6 mm) pockets dropped from 319 to 3, respectively. The combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) adjunctive to subgingival debridement may represent a valuable approach to improve the outcomes of non-surgical periodontal treatment.

Injection of Enriched Hyaluronic Acid for Vaginal Dryness in a Tamoxifen User

Studies indicate that &gt; 90% of breast cancer survivors taking adjuvant endocrine therapy as tamoxifen experience menopausal symptoms, including vaginal dryness and dyspareunia. Unfortunately, these sexual problems are closely related to depression and early discontinuation of treatment. The injectable use of cross-linked Hyaluronic Acid (HA) gel in the vaginal walls has demonstrated encouraging results in improving the symptoms of vaginal dryness but it was associated with non-thrombotic pulmonar embolism. We report the case of a young female patient, 39 years old, using tamoxifen for 4 years for preventing breast cancer recurrence, with vaginal dryness and dyspareunia, whose injection of a liquid formulation, containing non-cross linked hyaluronic acid, antioxidants and amino acids brought significant clinical improvement of sexual concerns.

Deformation characteristics of hydrogel products based on cross-linked hyaluronic acid.

The cross-linked hyaluronic acid (HA) fillers are the viscoelastic hydrogel with a dominant elasticity rather than a viscosity as a useful medical device in the soft tissue augmentation. These HA fillers undergo deformation to begin the biodegradation by the biochemical and physical environment of the body, and result of deformations are closely related to clinical performance. The specific equation of molding index is newly generated and proved with Collin's equation, which is used for strong elastomers, for selecting optimal product in facial treatment. In this study, the results of amplitude sweep test from five marketed HA fillers were mathematically demonstrated for the proper clinical application. The increment of loss modulus by deformation was evaluated as a useful factor for the maintenance of optimal shape molding performance and resistance to external deformation of the cross-linked HA gel. From this study, the equation of molding index for weak viscoelastic hydrogels like HA products can be applied for choosing which products even in aesthetic plastic field. This molding index equation is compared to Collins' equation that index of deformation as elastomer like rubber and then found the positive correlation between two equations. This study could provide a basic theory that achieve useful clinical performance according to characteristics among many types of medical devices based on the molding index.

A Preliminary Report on the Safety and Efficacy of a Novel MaiLi HA Filler for Facial Correction of Wrinkles, Folds, Volume and Lips

Introduction: The principal author was given the opportunity to assess new hyaluronic acid filler, first before its European Commission labeling during clinical investigations in France, and then after its European Commission labeling in his clinical practice in Geneva, Switzerland. This hyaluronic acid gel benefits from the world’s first patented OxiFree™ technology. This article sought to present preliminary safety and efficacy data from the first private patient series treated in Geneva with this cross-linked hyaluronic acid gel, called MaiLi. Material and methods: Like most of its competitors, MaiLi is available in various variants, including gel for filling fine wrinkles, for deeper wrinkles, folds, and for lip enhancement, in addition to gels for volumizing indications. This cohort study encompassed patients from the authors’ private esthetic clientele in Geneva, Switzerland. Depending on the indications, the injections were performed according to previously described techniques, ranging from the “blanching technique” to deeper injections. Results: Between January and November 2021, overall 45 patients aged 56 years on average were injected MaiLi gels, according to the areas they wished to be treated, with a follow-up period ranging from a few days to 12 months. Based on our current dataset, we confirm that MaiLi fillers have proven very safe, causing no unexpected undesirable effects. The gel’s hold over time related to its remarkable projection capacity was excellent, resulting in quite natural outcomes and a perfect integration into the tissues. These beneficial effects were still evident at 1-year follow-up. Conclusion: The MaiLi hyaluronic acid fillers proved to be well tolerated and safe, with long-lasting effects. Remarkable properties revealed in this follow-up were their projection capacity and suppleness, as well as their ease of use and longevity, resulting in full patient satisfaction. No relevant undesirable effects were observed. There were no edematous reactions following the injections, nor were there any lymphatic circulation disorders.

Hyaluronic Acid Fillers, Needle Contamination by Fastidious Microorganisms, and Risk of Complications.

Complications are becoming ever more common with the increased use of hyaluronic acid (HA) fillers in aesthetic medicine. Complications due to needle contamination with fastidious microorganisms are no exception. To perform, in a top Italian aesthetic medicine facility, what the authors think is the first monitoring program of microbial needle contamination of cross-linked HA gel fillers after the prefilled syringes with gel residues were stored for retouches after the first aesthetic procedure. Needle contamination monitoring study, performed between January and November 2019, on 35 needles (caliber, 30 and 27 G) stored at 4°C in their resealed filler packages for possible retouch after a first aesthetic treatment involving the middle and lower facial thirds. Women's age: 35 to 70 years old. The search for contaminating agents of the 3 monitored bacterial contaminants ( Staphylococcus aureus , Streptococcus pyogenes , and anaerobes) as well as yeasts and molds always tested negative. In the days and months after treatment, no patients in post-treatment controls showed evidence of infection in the treated areas. The observational retrospective study confirms that good storage conditions, including monitored refrigeration, avoid the risk of contamination of partially used HA gel fillers by fastidious microorganisms.

Efficacy of Cross-Linked Hyaluronic Acid Gel for the Reduction of Post-operative Obstructive Symptoms Due to Adhesions.

BackgroundAdhesions occur frequently after surgery. A number of methods are being employed for reducing post-operative adhesions. The purpose of this study was to determine the efficacy of hyaluronic acid gel in the reduction of post-operative bowel obstruction symptoms in patients undergoing emergency laparotomy due to small bowel perforation and presenting with peritonitis.MethodsIn this experimental study, 78 patients were evaluated. All had presented to the emergency department with peritonitis secondary to small bowel perforation. Exploratory laparotomy was performed and after thorough lavage, a loop stoma was formed on the right side of the abdomen with an injection of hyaluronic acid gel injected into the abdominal cavity before the closure of the abdomen. Postoperative obstructive symptoms at one, three, and six months were evaluated. All patients underwent stoma reversal at three months.ResultsObstructive bowel symptoms were seen in 18 patients (23.07%) patients. The cumulative incidence of obstructive symptoms at three months was only 8.97% but after the second intervention without protective gel, it increased to 23.07% at six months.ConclusionsCross-linked hyaluronic acid gel was effective in the reduction of post-operative bowel obstructive symptoms due to adhesions in patients who had presented with peritonitis due to small bowel perforation and had undergone exploratory laparotomy with stoma formation.

A Novel Method to Choose the Experimental Parameters in Large Amplitude Oscillatory Shear Rheology

Large Amplitude Oscillatory Shear (LAOS) rheology is a technique to analyze materials that are viscoelastic in nature. The raw values of stress and strain that were taken out from rheometer during the large amplitude oscillatory shear test are used in the constitutive models. The model parameters from the constitutive model are then analyzed on the materials being tested. Various test protocols and geometries will be used to analyze the materials of interest during LAOS rheological examination. The selection of test protocols and usage of geometry are less studied in testing various kinds of materials using LAOS. Cone and plate and parallel plate geometries are generally used for LAOS. The test protocols would be varying amplitude and varying frequencies. In the present work, quantification of relative performance of test protocols and geometry that have been used during the analysis of cross-linked poly vinyl alcohol hyaluronic acid (PVAHA) gels as material systems are studied using data envelopment analysis (DEA). The methodological approach using output oriented constant return to scale (CRS) and output oriented variable return to scale (VRS) are tested with the decision making units (DMU) as the geometry and test protocols used. These results are then combined with the Shannon's entropy to rank the efficient DMUs. Using Shannon's entropy combined with CRS and VRS, it is suggested that the use of parallel plate geometry with the test protocol of 0.5 rad/s and 50 frequency is best suitable for the cross-linked hyaluronic acid and poly vinyl alcohol gels examined.

Effect of Adding Lidocaine to Hyaluronic Acid Gel for Volume Loss Correction: A Preliminary Observation

Introduction: Although adding a local anesthetic is an effective way to reduce pain during intradermal Hyaluronic Acid (HA) injections, it is not clear if the pain control is as effective when performing injections close to the bone. The primary aim of these preliminary observations was to explore this issue. As a secondary aim, we wanted to assess if the addition of lidocaine alters the behavior of HA gel in the tissues over time. Subjects: Two women provided informed written consent to participate in the study. Participants were blind to the type of HA gel used for either temporal fossa. Methods: A cross-linked HA gel was used for the study. One side was injected with the gel with and the other without lidocaine, in no particular order. Photographs from the front, profile and three-quarter left and right and frontal MRI scans were taken before and just after the injections, then every 6 months for 2 years. Results: The side injected with the gel with lidocaine was significantly less painful than that injected without lidocaine. Both types of gel changed shape on MRI in the first 6 months but stayed stable thereafter till the end of our follow-up at 24 months. Based on MRI, patient reported outcomes and expert assessed aesthetic outcomes, using MAS® and the global aesthetic improvement scale, both types of gel were comparable. Conclusion: The addition of lidocaine to HA volumiser gels reduces pain to a remarkable degree.

Stability of Two Cross-Linked Hyaluronic Acid Gels for the Treatment of Temporal Fossa Volume Loss: A Preliminary Study Using MRI and Visual Observations

Introduction: Hyaluronic Acid (HA) gels are a commonly used option for correcting facial volume loss. Over the past 2 years, we have been testing the clinical results of two HA gels, without lidocaine, made by the same manufacturer using the patented “Inter- Penetrating NetworkLike” (IPN-Like) cross-linking technology. The aim of this work was to evaluate if there is a difference in the tissue stability and associated clinical outcomes between these two gels. Material and methods: A 67 and 75 years old Caucasian women, from our private aesthetic center, agreed to be injected with the different HA volumiser gel, one in each of their temporal fossae. The Stylage® XL and XXL HA gels (LABORATOIRES VIVACY, Archamps, France) were used for this study. The gels have different concentrations and levels of cross-linking, but have the same indications for correcting facial volume loss resulting from the ageing process. Clinical outcomes included assessing the degree of pain experienced by participants during and after injection using a Visual Analog Scale (VAS). Aesthetic improvement was evaluated using the Merz Analogic Scale® (MAS)® and Global Aesthetic Improvement Scale (GAIS) scales completed by patients and independent experts at different pre-set time-points using photographs taken from the front, profile and three-quarter left and right angles. Moreover, Serial magnetic Resonance Imaging (MRI) scans were used to assess the tissue behavior of the gels immediately after injection and then 6 monthly for 2 years. Results: Both gels led to an improvement in the patients’ clinical outcomes. This improvement persisted over time. The MRI scans showed that, at Day 0, the injected gel was spherical in shape and became elongated by 6 months. This appearance did not change throughout the follow-up period. The scans showed little resorption at 24 months. Conclusion: Despite the relatively advanced age of the two patients and the small quantities of gel injected, the IPN-Like cross-linked hyaluronic acid volumiser gels had a satisfactory sustainable clinical effect as assessed by patients and experts. There was a slight advantage in favor of the gel with the lower HA concentration but higher level of cross-linking (Stylage® XXL). Given the observed persistent effect of the gels in our preliminary observation, it is now important to conduct a larger study with longer follow- up.

A New Cross-Linked Hyaluronic Acid Gel for Preventing Adhesion After Thyroid Surgery: An Animal Study

Background: Revision of any neck surgeries is usually associated with increased rate of complications compared to the initial surgery due to adhesions. Especially, recurrent laryngeal nerve injury and hypoparathyroidism are most important postoperative complications of thyroid revision surgery. This study aimed to reveal anti-adhesive effects of cross-linked hyaluronic acid gel (NCHAG) in thyroid surgery.Materials and methods: This study was performed in 16 adult male rats who underwent hemithyroidectomy in the right lobe and randomized into two experimental groups: Group I (control group) was given any substance and Group II (NCHA group) received NCHA spray into their perithyroidal area. The rats were sacrificed after three weeks of thyroidectomy for assessment.Results: Gross adhesions score (x̄ = 2.500) was significantly higher in Group I than Group II (x̄=1.750; P = 0.031). Group II showed significantly less fibrosis compared to the Group I (P = 0.002). The rate of inflammation was found to be significantly higher in group I (P = 0.008). Vascular proliferation was not different between two groups (p=0.083).Conclusions: Our study showed that NCHA can reduce postoperative adhesion and might be effective in preventing fibrosis after the thyroidectomy. Although this study could not demonstrate that application of NCHA is able to reduce complication rate in revision neck surgery, it could be safely used after thyroidectomy and neck surgeries to prevent adhesions.

Healing of buccal gingival recessions following treatment with coronally advanced flap alone or combined with a cross-linked hyaluronic acid gel. An experimental study in dogs.

AimTo clinically and histologically evaluate in dogs the healing of gingival recessions treated with coronally advanced flap (CAF) with or without cross‐linked hyaluronic acid (HA).Materials and methodsGingival recession defects were surgically created on the vestibular side of both maxillary canines in 8 dogs. After 8 weeks of plaque accumulation, the 16 chronic defects were randomly treated with either CAF alone or CAF and HA‐gel (CAF/HA). Clinical and histological outcomes were evaluated at 10 weeks post‐surgically.ResultsCompared to baseline, the clinical measurements at 10 weeks revealed a statistically significant decrease in gingival recession for both CAF (p < 0.01) and CAF/HA (p < 0.001) groups. Statistically significant differences were found in clinical attachment level (p < 0.05) and width of gingival recession (p < 0.01) favouring the CAF/HA group. Bone formation was statistically significantly greater in the CAF/HA group than in the CAF group (1.84 ± 1.16 mm vs., 0.72 ± 0.62 mm, respectively, p < 0.05). Formation of cementum and connective tissue attachment were statistically significantly higher in the CAF/HA group compared with the CAF group (i.e. 4.31 ± 1.78 mm versus 2.40 ± 1.35 mm and 1.69 ± 0.98 mm versus 0.74 ± 0.68 mm, respectively (p < 0.05)).ConclusionsThe present data have for the first time provided histologic evidence for periodontal regeneration of gingival recession defects following treatment with CAF and HA.Clinical relevanceThe use of HA in conjunction with CAF may represent a novel modality for treating gingival recession defects.

Periodontal wound healing/regeneration of two-wall intrabony defects following reconstructive surgery with cross-linked hyaluronic acid-gel with or without a collagen matrix: a preclinical study in dogs.

In-vitro data have shown that cross-linked hyaluronic acid (HA) enhances the proliferative and migratory properties of cells involved in periodontal wound healing/regeneration, stabilizes the blood clot, reduces the inflammatory response, and facilitates angiogenesis. The aim of this study was to histologically evaluate the effects of cross-linked HA alone or combined with a collagen matrix (CM) on the periodontal wound healing/regeneration in intrabony defects. Two-wall intrabony defects (5 mm wide, 5 mm deep) were surgically created at the distal and mesial aspects of mandibular premolars in six beagle dogs. The 24 defects were randomly treated as follows: open flap debridement (OFD) + HA, OFD + CM, OFD + HA + CM (HA/CM), and OFD alone (control). At 2 months, the animals were euthanized for histologic evaluation. The HA (2.43 ± 1.25 mm) and HA/CM (2.60 ± 0.99 mm) groups yielded statistically significantly (P &lt; .05) greater formation of new attachment (ie, linear length of new cementum adjacent to newly formed bone, with inserting collagen fibers) compared with the OFD (0.55 ± 0.99 mm) group. Among the four treatment groups, the HA/CM group demonstrated the highest amount of regenerated tissues, although no statistically significant differences in any of the histometric parameters were observed between the HA and HA/CM groups. Within their limits, it can be concluded that cross-linked HA alone or combined with CM promotes periodontal wound healing/regeneration in two-wall intrabony defects in dogs.

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.

A Tumor Microenvironment Destroyer for Efficient Cancer Suppression.

The tumor microenvironment (TME) is composed of tumor cells, blood vessels, cancer-associated fibroblasts (CAFs), tumor extracellular matrix (ECM), et al. The TME is closely related to anticancer treatment outcome. In this manuscript, a multifunctional nanomedicine (denoted as ZDCMH NP), combining multiple TME destruction strategies into one delivery system, has been designed and fabricated. In brief, zinc phthalocyanine (ZnPc, a photosensitizer), bromopentacarbonylmanganese(I) (COMn, a CO donor), and losartan (Dup, a CAF inhibitor) were coloaded inside mesoporous silica nanoparticles (MSNs). After that, a cross-linked hyaluronic acid (HA) gel shell was encapsulated onto the surface of the MSNs to form ZDCMH NPs. After arriving at the tumor tissue, the HA gel shell could be degraded by hyaluronidase (HAase) in the ECM to trigger encapsulated drug release. After light irradiation, ZnPc generated abundant reactive oxygen species (ROS), which could provide photodynamic therapy (PDT) activity and induce COMn to release CO, which could improve the enhanced permeability and retention (EPR) effect to promote ZDCMH NP accumulation in tumor tissue. The released Dup could inhibit CAF activity and downregulate the collagen fiber concentration in the TME to promote the deep penetration of ZDCMH NPs inside solid tumors. In vitro and in vivo anticancer studies have indicated that the destruction of the TME by multiple strategies is very helpful for ZnPc to obtain satisfactory PDT efficiency.

Using cross-linked hyaluronic acid gel to prevent postoperative lumbar epidural space adhesion: in vitro and in vivo studies.

Hyaluronic acid prevents tissue adhesion after different surgeries. Physical barriers and inflammatory regulation have been suggested to be involved in the mechanism of these clinical effects. However, the molecular mechanism by which hyaluronic acid prevents epidural adhesion has not yet been reported. In the current in vivo studies, we investigated cross-linked hyaluronic acid gel in the regulation of scar gene expression, the accumulation of fibroblasts in scar tissue, and the prevention of epidural adhesion. The effect of cross-linked hyaluronic acid gel on the secretion of inflammatory factors was observed in vitro. In addition, to ensure the accuracy and reliability of the in vivo gene expression results, we used a cell model to detect the target genes in vitro. The expression levels of TGFβ1 and COL1A1 mRNA were decreased in the cross-linked hyaluronic acid gel-treated group, and the protein expression of levels TGFβ1 and COL1A1 were also reduced, as detected by Western blotting in vitro and in vivo (P < 0.05). Histomorphometry results demonstrated that the number of fibroblasts in the experimental group was significantly lower than that in the control group 2weeks postoperatively. Micro-CT scans showed that the cross-linked hyaluronic acid gel could reduce adhesion in the epidural space after laminectomy. Additionally, the cross-linked hyaluronic acid gel could inhibit IL-6 secretion. These results indicate that cross-linked hyaluronic acid gel can prevent epidural adhesion by inhibiting inflammatory factors, such as IL-6, and downregulating TGFβ1 and COL1A1 mRNA expression. These slides can be retrieved under Electronic Supplementary Material.