In vivo testing of novel nitric oxide-releasing nanoparticles for alleviating heart failure using the zebrafish embryo model.

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 µM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.

A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase-Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

Polyphenol-based targeted therapy for oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-ß1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-ß1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-ß1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-ß1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-ß1 and improved mouth opening in OSF rat model.

Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

OBJECTIVE: To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). PATIENTS AND METHODS: A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. RESULTS: Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. CONCLUSION: Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

Port Pocket Infections: Hydrogel Reduces Time to Healing and Clinic Visits Compared with Iodoform Gauze.

Pocket infections are an occasional complication of totally implanted central venous catheters. The purpose of this study was to compare the safety, efficacy, and efficiency of the use of hydrogel after port removal vs the conventional method of packed iodoform gauze. In a cohort of 31 patients, the hydrogel group (n = 13) healed significantly faster than the group treated with the conventional method (15.5 vs 26.8 d; P = .009) and required fewer scheduled clinic visits (1.2 vs 10.8; P < .001). There were no differences in complications. This study suggests that hydrogel effectively promotes healing of port pocket infections, with advantages over the established technique.

Hypoglycemic effect of insulin-loaded hydrogel-nanogel composite on streptozotocin-induced diabetic rats.

At present, how to increase insulin rapidly, availably and stably is still a conundrum in the treatment of diabetes mellitus. In vitro studies have shown that insulin can be released from hydrogel-nanogel composite according to the changes of glucose level. This study aimed to observe the glucose-lowering effects and evaluate the safety of the insulin-loaded hydrogel-nanogel composite in diabetic rats. We found that significant glycemic regulation could be observed up to 30 hours after subcutaneous injection, and the fasting blood glucose was reduced effectively. The result of an oral glucose tolerance test showed that the level of insulin expressed a stable increase from 0.5 hours to 3.5 hours, which led to a reduction of glucose with steady steps. Also, compared with Ins group, the Gel+Ins group showed slighter skin and pancreas damage, while the oxidative stress and inflammation response were similar to the normal control group. In conclusion, these results demonstrated that the glucose-lowering action of the insulin-loaded hydrogel-nanogel composite was superior to that of the regular insulin, and might thus become an insulin carrier in the future.

Evaluation of the activity of a chemo-ablative, thermoresponsive hydrogel in a murine xenograft model of lung cancer.

BACKGROUND: Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer. METHODS: In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice (n = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed. RESULTS: The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 (n = 6, p = 0.0001), with no associated damage of hepatic or renal tissue observed. CONCLUSIONS: Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.

Evaluation of a cell-based osteogenic formulation compliant with good manufacturing practice for use in tissue engineering.

Proper bony tissue regeneration requires mechanical stabilization, an osteogenic biological activity and appropriate scaffolds. The latter two elements can be combined in a hydrogel format for effective delivery, so it can readily adapt to the architecture of the defect. We evaluated a Good Manufacturing Practice-compliant formulation composed of bone marrow-derived mesenchymal stromal cells in combination with bone particles (Ø = 0.25 to 1 µm) and fibrin, which can be readily translated into the clinical setting for the treatment of bone defects, as an alternative to bone tissue autografts. Remarkably, cells survived with unaltered phenotype (CD73+, CD90+, CD105+, CD31-, CD45-) and retained their osteogenic capacity up to 48 h after being combined with hydrogel and bone particles, thus demonstrating the stability of their identity and potency. Moreover, in a subchronic toxicity in vivo study, no toxicity was observed upon subcutaneous administration in athymic mice and signs of osteogenesis and vascularization were detected 2 months after administration. The preclinical data gathered in the present work, in compliance with current quality and regulatory requirements, demonstrated the feasibility of formulating an osteogenic cell-based tissue engineering product with a defined profile including identity, purity and potency (in vitro and in vivo), and the stability of these attributes, which complements the preclinical package required prior to move towards its use of prior to its clinical use.

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

BACKGROUND Chronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model. MATERIAL AND METHODS The model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays. RESULTS P1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays. CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

Motion Preservation in Hallux Rigidus After Failure of Hydrogel Implantation: Treatment Considerations and a Report of 2 Cases.

Hallux rigidus is a common condition treated daily by surgeons worldwide. During the past decade, the standard treatment algorithm has been questioned by both patients and surgeons seeking alternatives to arthrodesis, which was previously considered the gold standard for advanced disease. Patients are living longer, and many have a more active lifestyle; thus, recreating and improving range of motion and achieving pain relief are increasingly desirable. The treatment spectrum and implant options for motion-preserving techniques in the metatarsophalangeal joint has been widened with the recent US Food and Drug Administration approval of a polyvinyl-alcohol hydrogel implant. In the controlled US Food and Drug Administration trial, the 2-year revision rate was 9.2% and all failures were revised to a first metatarsophalangeal arthrodesis. Outcomes comparison of these revisions to primary fusions showed less predictable pain relief and may warrant alternative treatment considerations, preferably those that allow for continuation of motion preservation. Revision of failed hydrogel implants to arthrodesis can be performed through various first metatarsophalangeal fusion techniques or, as introduced in this review, with a fourth-generation threaded hemiarthroplasty. Excellent 10-year results with primary hemiarthroplasty supported its use as revision procedure in 2 failed polyvinyl-alcohol implantations, preserving arthrodesis for future salvage if necessary. The purpose of this report was to outline a motion-preserving technique after failed hydrogel implants and describe preoperative, intraoperative, and postoperative considerations for optimized outcomes.

Complete regeneration of large bone defects in rats with commercially available fibrin loaded with BMP-2.

This study aimed at investigating in vitro and in vivo the efficiency of commercially available fibrin as a carrier for controlled and sustained bone morphogenetic protein-2 (BMP-2) release to induce bone formation and reduce the side effects of its use. In vitro release and activity of low-dose recombinant human BMP-2 (rhBMP-2) (37.5 µg/mL) embedded in commercially available fibrin were evaluated and, subsequently, critical-size femur defects in rats were grafted to study bone regeneration and vascularisation by micro-computed tomography (µCT) and histology. In vitro experiments showed a sustained BMP-2 release with a high BMP activity remaining after 28 d. In vivo, fibrin loaded with BMP-2 showed an extremely fast bone healing, with a large amount of new bone formation throughout the entire defect in the first 4 weeks and complete cortical repair and fusion after 8 weeks, with no ectopic bone formation. In contrast, the control fibrin group did not fuse after 12 weeks. Vascularisation was similar in both groups at 4 and 12 weeks after implantation. In conclusion, commercially available fibrin is a very efficient carrier for rhBMP-2 to graft critical-size cortical bone defects and might be a more optimal delivery vehicle for BMP-2-induced bone regeneration than currently available collagen sponges.

Interactions of Organosilanes with Fibrinogen and Their Influence on Muscle Cell Proliferation in 3D Fibrin Hydrogels.

Silanization of biomacromolecules has emerged as a fruitful approach to prepare hybrid biohydrogels. However, very little is known about interactions between organosilanes and biopolymers in solution. Here we focused on fibrin, a protein of interest in the biomedical field, whose self-assembly process and resulting gel structure are highly sensitive to experimental conditions. Three main silanes were selected to decipher the relative influence of the silanol groups and organic functions. Whereas no protein denaturation was observed, silanes bearing hydrophobic groups had a surfactant-like behavior and could improve the dispersion of fibrinogen molecules, impacting gel formation kinetics and rheological properties. 3D cultures of myoblasts evidenced that organosilanes could promote or impede cell proliferation, suggesting interactions of silanols with fibrin. These results demonstrate that the two sides of the coin of organosilane reactivity are relevant at different stages of fibrin gel formation and must be considered for future development of hybrid biomaterials.

Biocompatible Lipopeptide-Based Antibacterial Hydrogel.

A biocompatible hydrogel containing a hexapeptide as a key unit has been designed and fabricated. Our design construct comprises a ß-sheet-rich short hexapeptide in the center with a hydrophobic long chain and hydrophilic triple lysine unit attached at the N- and C-terminals, respectively. Thus, it is this amphiphilic nature of the molecule that facilitates gelation. It can capture solvent molecules in the three-dimensional cross-linked fibrillar networks. The amphiphilic character of the construct has been modulated to produce an excellent biocompatible soft material for the inhibition of bacterial growth by rupturing the bacterial cell membrane. This hydrogel is also stable against enzymatic degradation (proteinase K) and, most importantly, offers a biocompatible environment for the growth of normal mammalian cells due to its noncytotoxic nature as observed through the cell viability assay. From the hemolytic assay, the morphology of the human red blood cells is found to be almost intact, which suggests that the hydrogel can be used in biomedical applications. Thus, this newly designed antibacterial hydrogel can be used as both an antibacterial biomaterial and a biocompatible scaffold for mammalian cell culture.

Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues.

Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm- b-PLA- b-PEG- b-PLA- b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 °C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such a result was particularly highlighted by the inability of a PEG- b-PLA- b-PNIPAAm triblock analog of the same composition to gelify. The hydrogels degraded through hydrolysis of the PLA esters until complete mass loss due to the diffusion of the recovered PEG and PNIPAAm/micelle based residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neuroprotective drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels' micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable through a small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery.

Characterization of a novel polyvinyl alcohol/chitosan porous hydrogel combined with bone marrow mesenchymal stem cells and its application in articular cartilage repair.

BACKGROUND: Different substances are combined to compensate for each other's drawbacks and create an appropriate biomaterial. A novel Polyvinyl alcohol (PVA)/chitosan (CS) porous hydrogel was designed and applied to the treatment of osteochondral defects. METHODS: Hydrogels of various PVA/CS ratios were tested for physiochemical and mechanical properties in addition to cytotoxicity and biocompatibility. The hydrogels with the best PVA/CS ratio were used in the animal study. Osteochondral defects were created at the articular cartilage of 18 rabbits. They were assigned to different groups randomly (n = 6 per group): the osteochondral defect only group (control group), the osteochondral defect treated with hydrogel group (HG group), and the osteochondral defect treated with hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) group (HG-BMSCs group). The cartilage was collected for macro-observation and histological evaluation at 12 weeks after surgery. RESULTS: The Hydrogel with PVA/CS ratio of 6:4 exhibited the best mechanical properties; it also showed stable physical and chemical properties with porosity and over 90% water content. Furthermore, it demonstrated no cytotoxicity and was able to promote cell proliferation. The HG-BMSCs group achieved the best cartilage healing. CONCLUSIONS: The novel PVA/CS porous composite hydrogel could be a good candidate for a tissue engineering material in cartilage repair.

Topical hydrogels with escin ß-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity.

The physicochemical properties, stability, in vivo antihyperalgesic activity, and skin irritation potential of the carbomer hydrogels with the new chemical entity escin ß-sitosterol (ES) phytosome were characterized and compared with those containing escin. Physicochemical characterization of the hydrogels (performed 48 hr after preparation) included organoleptic examination, pH measurement, light microscopy, differential scanning calorimetry analysis and rheological tests. The obtained results showed that increasing concentration of the active substances within 1-5% affected the appearance (color and transparency) of the hydrogels, their pH, consistency, and rheological behavior. Unlike acidic escin, which was dissolved in the liquid phase of the pseudoplastic hydrogels E1-E5 and reduced their maximal apparent viscosity (ηmax ), minimal apparent viscosity (ηmin ), and hysteresis area (H) in comparison to the plain carbomer hydrogel, amphiphilic ES-enhanced ηmax , ηmin , and thixotropy of the hydrogels ES1-ES5, which is favorable for prolonged retention at skin surface. Evaluation of in-use stability of the hydrogels showed that organoleptic characteristics, flow behavior, and pH values could be preserved for 3 months under ambient conditions. The rat ear test results suggested that the hydrogels are safe to be used on human skin. Both escin and ES-loaded hydrogels exerted significant, concentration-dependent antihyperalgesic effect in inflammatory pain model in rats. ES-loaded hydrogels were significantly more effective than those loaded with escin. This is a first report on the antihyperalgesic effect of topically applied escin as well as ES in a model of inflammatory pain.

Periurethral injection therapy in women with stress incontinence. / Periurethral injeksjonsbehandling hos kvinner med stressinkontinens.

Periurethral injection offers an alternative to the current main method for surgical treatment of stress incontinence in women, which is a polypropylene sling that is placed without tension below the mid-urethra. Injection therapy is a simple, gentle method that provides significant improvement in the degree of leakage and quality of life, but the results are not on a par with the polypropylene sling. Injection therapy may be relevant when the main method is not suitable or desired.

Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy.

OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.