Hyaluronic Gel Research Articles

A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo

Traditional cell therapy technology relies on the maximum expansion of primary stem cells in vitro, through multiple passages and potential differentiation protocols, in order to generate the abundance of cells needed prior to transplantation in vivo. Implantation of in vitro over-expanded and pre-differentiated cells typically results in poor cell survival and reduced regeneration capacity for tissue repair in vivo. We hypothesized that implantation of primary stem cells, after a short time culture in vitro (passage number ≤p3), in combination with controlled release of relevant growth factors would improve in vivo cell viability, engraftment and tissue regeneration. The goal of this study was to determine whether the release of myogenic growth factors from a heparin-hyaluronic acid gel (hp-HA gel) could enhance in vivo cell survival, in-growth and myogenic differentiation of human urine-derived stem cells (USC) with a corresponding enhancement in graft vascularization, innervation and regenerative properties. Human USC were obtained from healthy adult donors (n = 6), expanded and then mixed with a hp-HA gel containing sets of growth factors known to enhance myogenesis (IGF1, HGF, PDGF-BB), neurogenesis (NGF, FGF) and angiogenesis (VEGF), or a cocktail with a combination of growth factors. Primary cultured USC (p3) mixed with the hp-HA gel and the various combinations of growth factors, were subcutaneously injected into athymic mice. In vivo cell survival, engraftment and functional differentiation within the host tissue were assessed. The implanted grafts containing USC and the growth factor cocktail showed the greatest number of surviving cells as well as increased numbers of cells that expressed myogenic and endothelial cell markers as compared to other groups 4 weeks after implantation. Moreover, the graft with USC and the growth factor cocktail showed increased numbers of blood vessels and infiltrating neurons. Thus, growth factors released in a controlled manner from an hp-HA gel containing USC efficiently improved in vivo cell survival and supported vascularization and myogenic differentiation within the grafts. This study provides evidence for the use of primary USC and growth factors in a hydrogel as a novel mode of cell therapy for the promotion of myogenic differentiation for the treatment of injured muscle tissue. Statement of significanceCell therapies are a promising treatment option for neuromuscular dysfunction disorders. However, major limitations in cell retention and engraftment after implantation remain a hindrance to the use of stem cell therapy for the treatment of muscle injuries or diseased tissues. Implanted long-term in vitro cultured cells tend to demonstrate low rates of survival and tissue engraftment, lessened paracrine effects, and poor homing and differentiation. Human USC are an easily obtainable stem cell source that possess stem cell characteristics such as a robust proliferative potential, paracrine effects on neighboring cells, and multi-potential differentiation. In this study, we demonstrated that a combination of primary human USC with a cocktail of growth factors combined in a hyaluronic gel was optimal for cell survival and engraftment, including myogenic differentiation potential of USC, angiogenesis and host nerve fiber recruitment in vivo. The present study also demonstrated that the use of primary urine derived stem cells at early passages, without in vitro pre-differentiation, implanted in a hyaluronic-heparin hydrogel containing a cocktail of growth factors, provided an alternative safe site-specific delivery method for cell therapy.

Application of the mixture of sodium hyaluronate gel and triamcinolone acetonide in intraocular surgery

Objective To observe the efficacy of application of the mixture of sodium hyaluronate gel and triamcinolone acetonide(TA) in complex vitreoretinal surgery. Methods Prospective study. Total of 80 eyes of 77 patients who underwent complex vitreoretinal surgery combined with silicone oil tamponade in the First Affiliated Hospital of Zhengzhou University from May to Oct. 2018 were collected. All cases were randomly divided into treatment group and control group. At the end of surgery, the 1∶1 mixture 0.1 ml of sodium hyaluronate gel and TA (2 mg) was injected into the vitreous cavity in the treatment group; while the control group received injection of 2 mg TA into the vitreous cavity. Results The distribution of mixture was more uniform and diffuse in the silicone oil eye of treatment group, while the distribution of TA in control group was more concentrated in lumps in the silicone oil eye. The particles of TA could be completely absorbed within 2 weeks in the treatment group, while in control group TA retained for 4-8 weeks. The early postoperative BCVA improvement rate was 88.89% in the treatment group and 43.18% in control group, respectively. The difference of BCVA improvement rate was statistically significant between the two groups (χ2=19.067, P=0.000). The incidence of intraocular hypertension was 30.56% (11/36) in the treatment group and 29.55% (13/44) in control group, respectively (χ2=0.010, P=0.557). The incidence of anterior chamber fibrin exudation in the two groups was 22.22%(8/36) and 15.91% (7/44), respectively(χ2=0.518, P=0.472). The incidence of proliferative vitreoretinopathy(PVR) in the two groups was 38.89% (14/36) and 38.64% (17/44), respectively(χ2=0.001, P=0.581). Conclusion The mixture of sodium hyaluronate gel and TA is more evenly distributed and absorbed faster in the silicone oil tamponade eye. It is more conducive to the early postoperative visual recovery and fundus observation. Key words: Surgery, vitreoretinal, complex; Vitreoretinopathy, proliferative; Sodium hyaluronate; Triamcinolone acetonide; Hypertension; Anterior chamber exudation

Effects of MAL-PDT, ingenol mebutate and diclofenac plus hyaluronate gel monitored by high-frequency ultrasound and digital dermoscopy in actinic keratosis - a randomized trial.

The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons. The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes. Patients with ≥5 Olsen II AKs in a 25cm2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area. Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS. MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots.

Reinforced macromolecular micelle-crosslinked hyaluronate gels induced by water/DMSO binary solvent.

Introducing macromolecular micelles into a biocompatible hyaluronic acid (HA) hydrogel is a promising strategy to improve its mechanical properties for biomedical applications. However, it is still unclear whether the solvent nature has an influence on the structure and property of HA gels especially when they are used for those cases containing binary solvents because reversible hydrophobic association within micelles could be weakened or even dissociated by organic solvents. In this work, we demonstrated that a binary solvent consisting of water and low-toxic dimethyl sulfoxide (DMSO), a commonly used cryoprotectant agent in biomedicine, can enhance the mechanical properties of hydrophobic-associated methacrylated hyaluronate (MeHA) gels crosslinked by diacrylated PEO99-PPO65-PEO99 (F127DA) macromolecular micelles, namely FH gels. The resulting FH hydro/organo-gels showed a crystalline structure due to polymer/solvent interactions. The FH gels showed a low swelling degree and the maximum strength (10.12 MPa), modulus (106.8 kPa) and toughness (1540 J m-2) in DMSO with a volume fraction of around 0.6. Moreover, the FH gels displayed a rapid recoverability under cyclic loading-unloading stress particularly in the presence of DMSO within the network due to their dual-dynamic dissipation networks. Such novel hydrophobic associated polysaccharide gels with tunable mechanical properties in binary solvents would be attractive in a cryopreservation system for cell-based applications.

In situ gel treatment for oral mucosal lesions: A systematic review

Aim: In situ gel systems present the unique property of converting from sol–gel upon biological stimulus. This study aimed to find various oral lesions treated with in situ gels and their outcome assessment. Materials and Methods: In this study, electronic and manual search was done to find the studies concerning the use of in situ gels as a single method of treatment and adjunct to oral lesions. A total of 22 articles were collected of which three clinical trials which fulfilled the inclusion criteria and published from 2011 to 2019 were included in the study. Literature review search revealed that there are no sufficient clinical trials performed on in situ gel treatment for oral lesions from 2011 to 2019. Results: The results of the study show that fluconazole can be used for oropharyngeal candidiasis, curcumin solid–lipid nanoparticle-loaded gels is more effective for oral erythroplakia, and 4% hyaluronic acid-containing topical gel formulation is effective in treating recurrent aphthous stomatitis. Quality assessment was done using Revman 5.3 for three studies, of which one study proved to have low risk of bias. Conclusion: It is concluded that using formulated in situ gels can be an alternative approach to treat various oral lesions locally by improving patient’s compliance. Further clinical trials concerning efficacy of in situ gels for treating oral lesions are still required.

Particle diffusion in extracellular hydrogels.

Hyaluronic acid is an abundant polyelectrolyte in the human body that forms extracellular hydrogels in connective tissues. It is essential for regulating tissue biomechanics and cell-cell communication, yet hyaluronan overexpression is associated with pathological situations such as cancer and multiple sclerosis. Due to its enormous molecular weight (in the range of millions of Daltons), accumulation of hyaluronan hinders transport of macromolecules including nutrients and growth factors through tissues and also hampers drug delivery. However, the exact contribution of hyaluronan to tissue penetrability is poorly understood due to the complex structure and molecular composition of tissues. Here we reconstitute biomimetic hyaluronan gels and systematically investigate the effects of gel composition and crosslinking on the diffusion of microscopic tracer particles. We combine ensemble-averaged measurements via differential dynamic microscopy with single-particle tracking. We show that the particle diffusivity depends on the particle size relative to the network pore size and also on the stress relaxation dynamics of the network. We furthermore show that addition of collagen, the other major biopolymer in tissues, causes the emergence of caged particle dynamics. Our findings are useful for understanding macromolecular transport in tissues and for designing biomimetic extracellular matrix hydrogels for drug delivery and tissue regeneration.

Cross-linked hyaluronan gel to improve pregnancy rate of women patients with moderate to severe intrauterine adhesion treated with IVF: a randomized controlled trial.

To evaluate whether the cross-linked hyaluronan (cHA) gel can improve the clinical pregnancy rate of patients with moderate to severe intrauterine adhesion (IUA) who underwent operative hysteroscopy followed by embryo transfer. Women with moderate to severe IUA desiring to undergo embryo transfer were recruited in this randomized controlled trial. The patients were randomized on the day of receiving hysteroscopy. The control group received standard hysteroscopy, while cHA gel was applied to the treatment group at the end of hysteroscopy and 5-7days after operation. All patients were expected to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection and frozen-thawed embryo transfer (FET). A total of 306 patients were enrolled in this study, of which 202 were assigned to the treatment group and 104 to the control group. Both the clinical pregnancy rate (26.3% [49/186] vs. 15.3% [13/85], P = 0.045), the implantation rate (17.7% [57/322] vs. 9.8% [15/153], P = 0.025), and the endometrial thickness on the day of embryo transfer (7.97 ± 1.37 vs. 7.50 ± 0.60mm, P < 0.001) were significantly higher in the treatment group compared to the control group. In addition, histological assessment of the paired endometrial tissues collected before and after operation revealed a relatively higher number of tubular glands after operation (15.1 ± 13.2 vs. 28.8 ± 30.4, P = 0.166). To conclude, the application of cHA gel in patients with moderate to severe IUA during hysteroscopy can improve the quality of endometrium and uterine receptivity and consequently enhance the clinical pregnancy rate after IVF/CSI and FET.

Reporting outcomes of hyaluronic gel filler as a treatment for epiblepharon

Epiblepharon occurs when an extra skin fold overlaps on the eyelid margin with the isolated form mainly seen in children of east Asian origin. If symptomatic and the use of conservative measures such as lubricants have failed, surgery is usually indicated. This traditionally involves everting sutures or combined skin excision, such as a modified Hotz procedure. However, a temporizing non-surgical alternative to a skin removal procedure, especially if the natural history is for improvement as the child grows older, would be ideal. This is a retrospective single-centre case review of epiblepharon cases treated with hyaluronic acid (HA; Restylane, Galderma UK) treated in the past 5years by a single surgeon (RM). Institutional review board approval was obtained. Success is defined as improvement or stabilization of the class and/or keratopathy score of the epiblepharon. Five patients were identified with epiblepharon between 2012 and 2017 who had hyaluronic acid filler to 8 eyelids. Six eyelids had improvement, 1 remained stable and 1 was worse equating to an 87% success rate; however, 2 opted for reversal using hyaluronidase due to aesthetic reasons. Two went on to have further surgery as they partially responded to filler treatment. This study provides further proof of concept that HA is a simple non-surgical and reversible option that may avoid the need for surgery for epiblepharon in selected cases. It may even be considered in older children or adolescents with the caveat that fullness may require hyaluronidase to dissolve.

Prospective comparative study of the use PRP and viscoelastic sodium hyaluronate gel in patients with grade ii knee osteoarthritis

The development of an effective and safe methods of conservative treatment of knee osteoarthritis of the has a priority in modern orthopaedics. Objective: to compare results of Platelet-Rich Plasma — PRP and PRP in combination with 2 % viscoelastic sodium hyaluronate gel (proFLEX INTRA) in patients with the II grade knee osteoarthritis.Methods: from 2018 to 2019 prospective randomized comparative study of the efficiency of using PRP therapy (group I) and PRP in combination with a 2 % viscoelastic sodium hyaluronate gel (proFLEX INTRA) (group II) was conducted in 50 patients with II grade knee osteoarthritis (aged between 48 and 73 years). Patients were assessed before treatment, 1, 3, and 6 months after treatment with the help of VAS while walking, WOMAC, and OKS scales. Laboratory assesment of inflammation markers in serum and synovial fluid were performed before treatment and 4 weeks after. Synovial fluid was examined by using clinical-microscopic and biochemical methods according to the following markers: cytosis, percentage of neutrophils, lymphocytes, synoviocytes and macrophages, protein, hyaluronic acid. In blood serum were determined: total protein, glycoproteins, chondroitin sulfates, alkaline phosphatase activity.Results: in II group was noted a statistically significant improvement according to VAS and WOMAC scale comparing with I group 6 months after treatment. The content of glycoproteins and chondroitin sulfates in blood serum of patients in the II group, also the protein content in synovial fluid, 4 weeks after treatment was lower (p &lt; 0.05) comparing with the I group. However, the content of HA was higher (p &lt; 0.05) in the II group of patients.Conclusions: both methods, PRP; PRP and HA allowed to reduce VAS pain score while walking and to improve joint function according to WOMAC and OKS scales in patients with the II stage knee osteoarthritis, six months after treatment. While, in the group of combined use PRP and 2 % viscoelastic sodium hyaluronate gel the results of treatment according to VAS and WOMAC scales were statistically significantly better and the inflammatory-dystrophic degree of changes in the knee was less comparing with the I group.

Prospective comparative study of the use prp and viscoelastic sodium hyaluronate gel in patients with grade ii knee osteoarthritis

The development of an effective and safe methods of conservative treatment of knee osteoarthritis of the has a priority in modern orthopaedics. Objective: to compare results of Platelet-Rich Plasma — PRP and PRP in combination with 2 % viscoelastic sodium hyaluronate gel (proFLEX INTRA) in patients with the II grade knee osteoarthritis.Methods: from 2018 to 2019 prospective randomized comparative study of the efficiency of using PRP therapy (group I) and PRP in combination with a 2 % viscoelastic sodium hyaluronate gel (proFLEX INTRA) (group II) was conducted in 50 patients with II grade knee osteoarthritis (aged between 48 and 73 years). Patients were assessed before treatment, 1, 3, and 6 months after treatment with the help of VAS while walking, WOMAC, and OKS scales. Laboratory assesment of inflammation markers in serum and synovial fluid were performed before treatment and 4 weeks after. Synovial fluid was examined by using clinical-microscopic and biochemical methods according to the following markers: cytosis, percentage of neutrophils, lymphocytes, synoviocytes and macrophages, protein, hyaluronic acid. In blood serum were determined: total protein, glycoproteins, chondroitin sulfates, alkaline phosphatase activity.Results: in II group was noted a statistically significant improvement according to VAS and WOMAC scale comparing with I group 6 months after treatment. The content of glycoproteins and chondroitin sulfates in blood serum of patients in the II group, also the protein content in synovial fluid, 4 weeks after treatment was lower (p &lt; 0.05) comparing with the I group. However, the content of HA was higher (p &lt; 0.05) in the II group of patients.Conclusions: both methods, PRP; PRP and HA allowed to reduce VAS pain score while walking and to improve joint function according to WOMAC and OKS scales in patients with the II stage knee osteoarthritis, six months after treatment. While, in the group of combined use PRP and 2 % viscoelastic sodium hyaluronate gel the results of treatment according to VAS and WOMAC scales were statistically significantly better and the inflammatory-dystrophic degree of changes in the knee was less comparing with the I group.

Superparamagnetic Nanoparticle Delivery to the Cochlea Through Round Window by External Magnetic Field: Feasibility and Toxicity.

Introduction. The objective of this study was to evaluate the feasibility and toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) administered into the cochlea through the round window (RW) by an external magnetic field. Materials and Methods. In 5 Wistar rats, the left RW was punctured. SPIONs suspended in hyaluronic gel (5 mg/mL) were applied in the RW niche and covered by a muscle graft. The nanoparticles were mobilized using a rare earth magnet (0.54 T) held in 4 consecutive positions around the head. The right ear served as control. Hearing function was monitored by auditory brainstem responses (4-32 kHz tone bursts). Results. The auditory thresholds remained unchanged 1 month after the administration. The histological study of the cochleae showed that SPIONs were driven into the scala tympani in the basal turn, the second turn, and the apex. Conclusion. Superparamagnetic nanoparticles can be driven inside the cochlea toward the apex with a preserved hearing up to 1 month in rats.

Host response in vivo and the expression of IL-4 in different cross-linked hyaluronic acid composite gels

Objective To observe the host response and the expression of interleukin-4(IL-4) in different cross-linked hyaluronic acid composite gels at different time points after the implantation in vivo, and to explore the significance of biocompatibility and macrophage polarization in post-implantation inflammatory response and tissue remodeling. Methods New Zealand white rabbits were respectively injected with crosslinked hyaluronic acid-crosslinked hydroxypropyl methylcellulose gel (sample 1), crosslinked hyaluronic acid-hydroxypropyl methylcellulose gel (sample 2) and commercially available modified sodium hyaluronate gel (control) in subcutaneous tissue at both sides of the spine. Then the rabbits were dissected at 1, 4 and 12 weeks after the implantation. The tissues were fixed with 10% formaldehyde solution, embedded in paraffin and sliced. Hematoxylin-eosin (HE) staining was performed to observe the degree of inflammation and fibrosis. Masson staining was performed to observe the formation of collagen fibers. Immunohistochemical staining was performed to observe the expression of IL-4. Results The results of HE staining showed that the inflammatory reaction in the sample 1 and sample 2 groups was significantly higher than that in the control group 1 and 4 weeks after the implantation. The inflammatory cells aggregated, and the wall of capsule and microcapsule was thick. The sample 1 group was more obvious, and the result was mild stimulation. For all the groups, the results were all non-irritating at 12 weeks after the implantation. The results of Masson staining showed that the collagen fibers in the sample 1 and sample 2 groups were increased compared with the control group, mainly distributed around the implantation site, and a small amount among the gels after 1 and 4 weeks. After 12 weeks, the collagen fibers were further increased, especially among the gels, which were consistent with the control group. The results of immunohistochemical staining showed that, at the same time point, the expression of IL-4 in sample 1 and sample 2 groups was higher than that in the control group, and the expression of IL-4 increased gradually with time. The expression of IL-4 in the control and sample 1 group at 12 weeks after the implantation was higher than that at 1 and 4 weeks respectively, and the differences were statistically significant (all P<0.05). In the sample 1 group, the expression of IL-4 at 12 weeks after the implantation was higher than that at 1 week, and the difference was statistically significant (P<0.05). The expression of IL-4 in the sample 1 group was significantly higher than that in the control group at 4 weeks after the implantation, and the difference was statistically significant (P<0.05). Conclusions The two different cross-linked sodium hyaluronate composite gels have good biocompatibility. The formation of collagen fiber and the expression of IL-4 can gradually increased within 12 weeks after the subcutaneous implantation, which is beneficial to the tissue remodeling. Key words: Hyaluronic acid; Gels; Cross-linked; Host response; Interleukin-4

Diode laser assisted excision of a gingival pyogenic granuloma: A case report.

Pyogenic granuloma is a non-neoplastic, exuberant, reactive lesion seen in response to local irritation or trauma caused by dental calculus, bacterial plaque, caries and restorations, with a strong predilection for the gingiva. It is among the frequently encountered oral lesions, occurring at a challenging oral site, the gingiva. Herein, we report a 71-year-old medically compromised Caucasian female who presented with a relatively large lobulated pyogenic granuloma on the buccal gingiva of the maxillary molar-premolar region. Total surgical excision was performed with an 840nm diode laser followed by the placement of hyaluronate gel and relevant periodontal dressing. Two weeks after surgical excision, complete healing was observed, but patient denied replacement of dental restoration. After 4 months of follow-up, an overall reduction of associated teeth mobility was also observed, with a minor recurrence in gingival inflammation. The objective of this report is to briefly review clinical, radiographic and histological findings of pyogenic granuloma along with a detailed discussion on its management through a diode laser.

Ligustrazine nanoparticles nano spray's activation on Nrf2/ARE pathway in oxidative stress injury in rats with postoperative abdominal adhesion.

Postoperative abdominal adhesions formation is considered a significant clinical entity implicating the healing process following major pelvic and abdominal surgery, with serious clinical complications and need for substantial health care expenditures. However, setting a physical barrier between the damage site and the neighboring tissues is a convenient and highly valid way to minimize or prevent peritoneal adhesions. The present experimental study evaluated the preventive effect of ligustrazine nanoparticles nano spray (LNNS) on postoperative abdominal adhesion in rats and explored its mechanism. Sixty male Sprague Dawley (SD) rats were randomly divided into sham operation group, control group, sodium hyaluronate group and low, medium, and high dose LNNS groups. All groups were prepared with abdominal adhesion models except for the sham operation group. The models were made by opening the abdominal cavity to and filing the serosa in ileocecal junction. The abdominal cavity of rats in the sham operation group were only opened and sutured. The wound surface of rats in the sodium hyaluronate group, low, medium, and high dose LNNS groups were sprayed with sodium hyaluronate gel (0.5 mL/kg) and LNNS (2.5, 5, and 10 mL/kg). Rats in each group were sacrificed 7 days later. Degree of adhesion was evaluated by naked eyes and the pathological sections were scored afterwards. The collagen synthesis in adhesion tissues was detected by Masson's trichrome stain, and the activities of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in peritoneal fluid were detected with the method of chromogenic substrate. Levels of TNF-α and IL-1β in serum, and the protein levels of MCP-1 and MMP-9 in adhesion tissues were detected by ELISA and. immunohistochemistry respectively. RT-PCR and Western blot were utilized to identify the expression levels of Nrf2, heme-oxygenase-1, NQO1 mRNA and protein in adherent intestinal tissues. Compared with the control group, the incidence of postoperative abdominal adhesions decreased in the low, medium and high dose LNNS groups, while the expression of SOD in the peritoneal fluid significantly increased. The expression levels of ROS, MDA and NO were reduced remarkably (P<0.05), so were the expression levels of serum TNF-α and IL-1β (P<0.01) and the expression of MCP-1 protein in adhesion tissues. The MMP-9 protein expression, and Nrf2, heme-oxygenase-1, NQO1 mRNA and protein expressions increased. LNNS with medium or high dose can significantly reduce the incidence of postoperative abdominal adhesions, the mechanism of which may be the activation of Nrf2/ARE pathway, resulting in the up-regulation of Nrf2, heme-oxygenase-1, NQO1 and mRNA expression, as well as the levels of TNF-α and IL-1β in peripheral blood and the expression of MCP-1 protein in adhesion tissues. Meanwhile, the content of MMP-9 protein in adhesion tissues were raised, and oxidative stress and inflammatory response are released.

New Cross Linked Hyaluronan Gel After Deep Infiltrating Endometriosis Surgery

New Cross Linked Hyaluronan Gel After Deep Infiltrating Endometriosis Surgery

The material properties of naked mole-rat hyaluronan

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring-like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.

Hyaluronate gel injection for rectum dose reduction in gynecologic high-dose-rate brachytherapy: initial Japanese experience.

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose–volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18–1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours.

Correction to Soft Hyaluronic Gels Promote Cell Spreading, Stress Fibers, Focal Adhesion, and Membrane Tension by Phosphoinositide Signaling, Not Traction Force.

Correction to Soft Hyaluronic Gels Promote Cell Spreading, Stress Fibers, Focal Adhesion, and Membrane Tension by Phosphoinositide Signaling, Not Traction Force.

Randomized Double-Blind Controlled Study on the Safety and Efficacy of a Novel Injectable Cross-linked Hyaluronic Gel for the Correction of Moderate-to-Severe Nasolabial Wrinkles

The current study compares two hyaluronic acid fillers, Ial System Duo and Belotero Basic/Balance, for the treatment of wrinkles. This is a single-center, double-blind randomized controlled study. Inclusion criteria consisted of subjects with bilateral nasolabial wrinkles. Each subject was treated with both products: One was applied on the right side and the other on the left side of the face. The quantity of product injected and any problems or local reactions (erythema, edema, pain or itching) were recorded and reassessed at 3 and 6months and then monthly until complete absorption of the product. The Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS) were used for the assessment, as well as an ultrasound measurement of the skin thickness. Complete data were available for 59 subjects. At 3 and 6months, both products showed improvement in the WSRS and GAIS score in the areas treated compared to pre-treatment assessments, although no significant differences were observed between them. No resulting significant differences were observed on skin thickness among the two products, which were completely reabsorbed in 285 ± 34days (Ial System Duo) and 277 ± 34days (Belotero Basic/Balance; Student's t test: p = 0.2181). No significant differences were observed with regard to the subject's satisfaction and adverse events. The Ial System Duo achieves long-term permanence (more than 9months confirmed by ultrasound) in correction of moderate and severe wrinkles, similar to Belotero Basic/Balance. Both products showed a high safety profile and a high degree of subject and physician satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

New Crosslinked Hyaluronan Gel, Intrauterine Device, or Both for the Prevention of Intrauterine Adhesions.

Background and Objectives:To compare the efficacy of 3 different techniques for prevention of adhesion reformation after hysteroscopic adhesiolysis in patients with moderate-to-severe intrauterine adhesions. Short-term assisted reproductive outcomes were also compared.Study Design:Total of 72 cases were randomized to Lippes loop intrauterine device (IUD) only, IUD plus a new crosslinked hyaluronan (NCH) gel, or NCH gel only following hysteroscopic adhesiolysis. All cases received hormonal therapy and a second hysteroscopy was carried out. Endometrial thickness values were measured using transvaginal ultrasonography and American Fertility Society adhesion scores were noted during first and second hysteroscopy in all groups. Reproductive outcomes were also compared for those who received in vitro fertilization treatment.Results:Transvaginal ultrasonography revealed significantly better endometrial thickness in the IUD+NCH (7.5 mm) and NCH-only groups (6.5 mm) than the IUD-only group (5 mm) (P < .001). All groups revealed enhanced but comparable American Fertility Society adhesion scores on second-look hysteroscopy. A total of 37 patients received in vitro fertilization treatment after surgical management of adhesions. Ongoing pregnancy rates after in vitro fertilization were 27%, 40%, and 36% in IUD, IUD+NCH, and NCH groups, respectively. However, the difference between the groups did not reach statistically significant difference.Conclusion:All interventions are of similar efficacy in the prevention of adhesion reformation after hysteroscopic adhesiolysis for moderate to severe intrauterine adhesions. However, better endometrial thickness values were observed in those who received NCH gel either alone or in combination with IUD. Assisted reproductive outcomes of both groups were comparable for ongoing pregnancy rates.