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Objective: To observe the clinical effect of mometasone furoate cream sodium Alginate Skin Repair Mask in the treatment of atopic dermatitis (AD). By assessing the combined use of these two treatments, the study aims to address a gap in knowledge regarding the effectiveness and safety of adjuvant therapies for AD, particularly in the context of Alginate Skin Repair Mask., Methods: Eighty patients were enrolled, including 42 males and 38 females aged 20-47 years, with an average age of (32.52±5.57) years, from July 2021 to July 2022, and the patients were divided into a single group (n=40) and a combined group (n=40) by random number table method. The patients in the single group were treated with mometasone furoate cream alone, and the patients in the combination group were treated with Alginate Skin Repair Mask on the basis of the treatment of the patients in the single group. The outcome measurements included clinical treatment effect, condition change (SCORAD score), quality of life (DLQI score), adverse reactions and disease recurrence were compared between the two groups. Both groups received treatment for 1 month. After the treatment of the patients, they were followed up for a period of 3 months., Results: The total effective rate of the single group was 80.0% (32/40), and that of the combined group was 97.5% (39/40) (P < .05). After treatment, the skin lesion area score, skin lesion degree score, pruritus insomnia score, and SCORAD total score in the combined group were significantly lower than those in the single group (35.03±9.41 vs 44.03±12.04) (all P < .05). The DLQI score of the combined group after treatment was significantly lower than that of the single group (3.72±1.53 vs 6.98±2.16) (P < .05). The incidence of adverse reactions in the single group was 22.5% (9/40), and the disease recurrence rate was 32.5% (13/40), while the incidence of adverse reactions in the combination group was 2.5% (1/40). The disease recurrence rate was 7.5% (3/40), and the incidence of adverse reactions and disease recurrence rate in the combination group were significantly lower than those in the single group (7.314, 7.812)., Conclusion: Mometasone furoate cream sodium Alginate Skin Repair Mask has an ideal clinical effect in the treatment of atopic dermatitis. Compared with single mometasone furoate cream, the combination of sodium Alginate Skin Repair Mask can further improve the patient's condition, improve the quality of life of the patient, and reduce the risk of adverse reactions and disease recurrence. The higher total effective rate in the combined group indicates that the addition of Alginate Skin Repair Mask to the treatment regimen resulted in improved outcomes for patients with atopic dermatitis (AD). This translates to better control of the disease, reduction in symptoms, and overall improvement in the patient's condition.  However, it is important for clinicians to be aware that the use of topical glucocorticoids like mometasone furoate cream can potentially lead to adverse reactions. Some documented adverse reactions associated with long-term use of topical glucocorticoids include acne-like eruption, telangiectasia (dilation of small blood vessels), and local skin atrophy. By addressing multiple aspects of AD management, including skin barrier repair, moisturization, and inflammation control, the combination of mometasone furoate cream and Alginate Skin Repair Mask provides a more comprehensive treatment approach. This comprehensive approach may contribute to the observed reduction in recurrence rate in the combination group compared to the single group, where only mometasone furoate cream was used.

Objective: To investigate the minimum therapeutic duration for patients with primary laryngopharyngeal reflux disease (LPRD) through the evaluation of symptom changes at multiple time points., Study Design: Prospective uncontrolled., Setting: University medical center., Methods: Patients with LPRD at the 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring were recruited from the European Reflux Clinic. Depending on the type of LPRD, patients were treated with a combination of proton-pump inhibitors, alginate, or magaldrate. Symptoms were evaluated with the reflux symptom score (RSS) at baseline and throughout treatment (1-, 3-, 6-, and 9-month posttreatment). The most appropriate therapeutic duration was determined using the RSS changes. Signs were evaluated with the reflux sign assessment., Results: A total of 159 patients completed the study. The mean age was 49.9 ± 15.7 years. At 1-month posttreatment, 97 patients (61.0%) were considered as early responders to treatment, and the treatment was stopped for 52 patients (32.7%). Of the 62 early nonresponders, 34 patients (21.4%) reached responded to treatment after 3 to 9 months. The cumulative therapeutic success rate at 1-month posttreatment (61.0%) progressively increased to reach a range of 82.4% to 99.3% at 9-month posttreatment. The RSS mainly decreased in the first month of treatment in early responders. In early nonresponders, RSS progressively decreased throughout the 9-month treatment period. The baseline severity of RSS is a strong predictor of therapeutic response., Conclusion: A therapeutic regimen of 1 month can be sufficient to treat one third of LPRD patients. The early nonresponders may require 3 to 9 months of treatment., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Abstract: In this case report, the authors summarize their experience of using hydrogel combined with alginate dressings in the wound care of a patient with grade 4 acute radiation dermatitis. With the combination of hydrogel and alginate dressings, the authors achieved autolytic debridement of the wound and created a moist healing environment to facilitate wound closure. Hydrogel helps the dressing adhere better to the wound bed, ensuring that it does not easily detach during the wound healing process. It also eliminates the need for traditional adhesive tapes for fixation, thus avoiding damage to the fragile skin in the radiation field.The wound gradually decreased in size from an area of 10 × 12 cm, and exudate decreased continuously. The wound completely healed in 20 days with a total of 17 dressing changes. As the wound gradually healed, the patient's psychological burden decreased and comfort level increased. The patient expressed satisfaction and hope for the gradual healing of the wound.Thus, the treatment of severe acute radiation dermatitis with hydrogel combined with alginate dressings yields remarkable results, aligning the noninvasive, low-adhesive, absorbent, conformable, and comfortable attributes of optimized wound care. This experience provides a practical foundation for wound management in acute radiation dermatitis and supports clinical application and promotion of the approach., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is no consensus on the best intervention for topical management of bleeding in malignant wounds. Although surgical hemostatic dressings are recommended, the use of calcium alginate (CA) is frequent among practitioners., Objective: The aim of this study was to evaluate the hemostatic efficacy of oxidized regenerated cellulose (ORC) and CA dressing in the management of bleeding from malignant wounds resulting from breast cancer., Methods: This was a randomized open clinical trial. The outcomes measured were total time to hemostasis and the number of hemostatic products used., Results: Sixty-one patients were potentially eligible for the study, 1 did not consent, and 32 were assessed to be ineligible, resulting in a sample of 28 who were randomized to 2 study groups. Total time to hemostasis was 93.8 seconds in the ORC group, with an average of 30.1 seconds (95% confidence interval, 18.6-189 seconds), and 67 seconds in the CA group, with an average of 30.4 seconds (confidence interval, 21.7 seconds to imprecise upper limit). The main difference was 26.8 seconds. Kaplan-Meier log-rank test, and Cox model showed no statistical significance ( P = 0.894). A total of 18 hemostatic products were used in the CA group and 34 in the ORC group. No adverse effects were identified., Conclusions: Although no significant differences were identified in terms of time, more hemostatic products were used in the ORC group, highlighting the effectiveness of CA., Implications for Practice: Calcium alginate may be the first choice in the management of bleeding in malignant wounds, favoring nursing in the most immediate hemostatic actions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ovarian cancer, characterized by high lethality, presents a significant clinical challenge. The standard first-line treatment is surgery and chemotherapy; however, postoperative chemotherapy is often ineffective and associated with severe side effects and the development of drug resistance. Consequently, there is an urgent need for innovative drug delivery strategies to enhance therapeutic efficacy. Natural polysaccharide polymers with high bioactivity have been extensively investigated for use alone or as adjuvants to chemotherapy and radiotherapy, and also for the preparation of efficient delivery systems for ovarian cancer therapy. This paper aims to review recent advances in the application of natural polysaccharides, including hyaluronic acid, chitosan, alginate, and cellulose, in the therapy of ovarian cancer. This paper primarily discusses the anti-tumor properties inherent to these natural polysaccharide polymers and offers a summary of their role in delivery systems used in ovarian cancer therapy., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Severe bleeding has caused significant financial losses as well as a major risk to the lives and health of military and civilian populations. Under some situations, the natural coagulation mechanism of the body is unable to achieve fast hemostasis without the use of hemostatic drugs. Thus, the development of hemostatic materials and techniques is essential. Improving the quality of life and survival rate of patients and minimizing bodily damage requires fast, efficient hemostasis and prevention of bleeding. Alginate is regarded as an outstanding hemostatic polymer because of its non-immunogenicity, biodegradability, good biocompatibility, simple gelation, non-toxicity, and easy availability. This review summarizes the basics of hemostasis and emphasizes the recent developments regarding alginate-based hemostatic systems. Structural modifications and mixing with other materials have widely been used for the improvement of hemostatic characteristics of alginate and for making multifunctional medical devices that not only prevent uncontrolled bleeding but also have antibacterial characteristics, drug delivery abilities, and curing effects. This review is hoped to prepare critical insights into alginate modifications for better hemostatic properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Bacterial cellulose (BC) has shown high capacity for the treatment of wounds and burns, providing a moisty environment. Calcium alginate can be associated with BC to create gels that aid in wound debridement and contribute to appropriate wound healing. This study is aimed at characterizing and evaluating the use of bacterial cellulose/alginate gel in skin burns in rats., Methods: Cellulose and cellulose/alginate gels were compared regarding the capacity of liquid absorption, moisture, viscosity, and potential cytotoxicity. The 2nd degree burns were produced using an aluminum metal plate (2.0cm) at 120ºC for 20s on the back of rats. The animals were divided into non-treated, CMC(Carboxymethylcellulose), Cellulose(CMC with bacterial cellulose), and Cellulose/alginate(CMC with bacterial cellulose and alginate). The animals received topical treatment 3 times/week. Biochemical (MPO, NAG and oxidative stress), histomorphometry and immunohistochemical assays (IL-1β IL-10 and VEGF) were conducted on the 14th, 21st, 28th, and 35th days., Results: Cellulose/Alginate gel showed higher absorption capacity and viscosity compared to Cellulose gel, with no cytotoxic effects. Cellulose/alginate presented lower MPO values, a higher percentage of IL-10, with greater and balanced oxidative stress profile., Conclusions: The use of cellulose/alginate gel reduced neutrophils and macrophage activation and showed greater anti-inflammatory response, which can contribute to healing chronic wounds and burns.

Objective: Burn injuries pose a heightened risk of infection, which is primarily responsible for increased morbidity and mortality. Factors such as extensive skin damage and compromised immunity exacerbate this vulnerability. Pseudomonas aeruginosa and Staphylococcus aureus are frequently identified in burns, with Gram-negative Pseudomonas aeruginosa often resistant to antibacterial agents. While Flaminal, an alginate-based wound dressing (Flen Health, Belgium), aids wound healing, its antibacterial effects are limited compared with 1% silver sulfadiazine (1% SSD). In contrast, Prontosan Wound Gel X, a betaine and polyhexanide-based hydrogel (B. Braun Medical AG, Switzerland), has been shown to effectively combat various microbes and promotes wound healing., Method: In this study, two research cohorts were retrospectively established (control group: patients receiving standard of care with the alginate-based wound dressing; intervention group: patients receiving the polyhexanide hydrogel wound dressing), comprising patients admitted to a burn centre between 2019 and 2022. Patients were eligible when continuous wound treatment with either of the two wound dressings was performed. Laser Doppler imaging (LDI) scans were conducted. Regions of interest (ROIs) were selected based on LDI scans and divided into healing time categories. Wound swabs were collected and the presence of Pseudomonas aeruginosa and Staphylococcus aureus was documented. Bacterial load was evaluated using a semiquantitative scale. Wound healing was recorded., Results: The control group consisted of 31 patients with 93 ROIs, while the intervention group had 67 ROIs involving 29 patients. Both groups exhibited similar proportions of healing time categories (p>0.05). The polyhexanide hydrogel dressing outperformed the alginate-based dressing in antiseptic efficacy by significantly reducing the incidence of Pseudomonas aeruginosa - and Staphylococcus aureus -positive cultures in patients' wounds. Wound healing time for conservative treatment was comparable between groups., Conclusion: In this study, the polyhexanide hydrogel dressing minimised Pseudomonas aeruginosa and Staphylococcus aureus colonisation in burn wounds, demonstrating strong antibacterial properties, emphasising its potential to minimise infections in burn injuries.

The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG- g -poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.

Inflammation and oxidative stress contribute to noncommunicable diseases (NCDs), with macrophages playing pivotal roles. Glycated collagen through Maillard-type glycation holds promise for enhancing anti-inflammatory properties, but its mechanism remains unclear. This study investigates the cellular mechanism and aims to contribute to expanding collagen utilization. Collagen was glycated with alginate oligosaccharide (AO) and glucose (Glc: as a comparative case) at 60 °C and 35% relative humidity for up to 24 h (C-AO and C-Glc, respectively). The anti-inflammatory activities of both C-AO and C-Glc were evaluated using an LPS-stimulated macrophage model. 18 h AO-glycated collagen (C-AO18 h) was found to significantly reduce the production of nitric oxide and proinflammatory cytokines (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). In contrast, C-Glc did not exhibit enhanced anti-inflammatory activity during any of the glycation periods. The enhanced anti-inflammatory activity of C-AO18 h was attributed to its downregulating effect on LPS receptors (toll-like receptor 4, Tlr4 ; cluster of differentiation 14, Cd14 ) and myeloid differentiation primary response 88 ( Myd88 ) mRNA expression, with suppression in receptor expression resulting in decreased phagocytic ability of macrophages against E. coli . In addition, compared with intact collagen, C-AO18 h exhibited improved antioxidant activity in the LPS-stimulated macrophage model, as it significantly upregulated superoxide dismutase (SOD) and catalase (CAT) activities while reducing malondialdehyde (MDA) levels. Overall, this study contributes to the development of collagen-based functional foods for mitigating inflammation and oxidative stress in NCDs.

This meta-analysis evaluates the efficacy of silver alginate dressings (SAD) compared to standard gauze (SG) in enhancing wound healing and reducing scar formation post-mastectomy in patients with triple-negative breast cancer. From an initial pool of 1245 articles, five studies met the inclusion criteria. The analysis revealed that SAD significantly improve early wound healing 1 week post-mastectomy, as indicated by lower Redness, Edema, Ecchymosis, Discharge, and Approximation (REEDA) scales (I 2  = 85%; Random: SMD: -7.08, 95% CI: -8.26 to -5.98, p < 0.01), compared to SG. Additionally, long-term scar outcomes measured by the Manchester Scar Scale (MSS) 5 months post-mastectomy showed a notable reduction in scar formation (I 2  = 95%; Random: SMD: -12.97, 95% CI: -16.20 to -9.75, p < 0.01)) in the silver alginate group. The findings support the use of SAD in post-mastectomy care for triple-negative breast cancer patients but highlight the need for further research on long-term safety and cost-effectiveness., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Myocardial Infarction (MI) is major cause of heart failure, highlighting the critical need for effective therapeutic strategies to improve cardiac repair. This study investigated the cardioprotective effects of VX765-coated polyethyleneimine (PEI)/sodium alginate (AG) composite nanogels (AG/PEI-VX765 NGs) in a rat model of MI. Additionally, AG-VX765 NGs and PEI-VX765 nanospheres (NPs) were synthesized and tested to compare their efficacy. MI was caused in rats by ligating the left anterior descending branch of the coronary artery, and the rats were grouped and set as Sham, MI, MI + VX765, MI + AG-VX765NGs, MI + PEI-VX765NPs, and MI + AG/PEI-VX765NGs. Results demonstrate that AG/PEI-VX765NGs were non-toxic and exhibited a sustained release of VX765. In vivo, experiments demonstrated that all treatment groups significantly enhanced cardiac function, reduced infarct size, fibrosis, and apoptosis in rats with MI, with the MI + AG/PEI-VX765NGs group exhibiting the most favorable outcomes. Our findings indicate that AG/PEI-VX765NGs represent a promising therapeutic approach for MI treatment., (© 2024. The Author(s).)

Purpose: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are common gastrointestinal disorders with extraesophageal manifestations (EGERD). Studies showed a correlation between GERD/LPR and ocular discomfort. Our aim was to report the prevalence of ocular involvement in patients with GERD/LPR, describe clinical and biomolecular manifestations, and provide a treatment strategy for this novel EGERD comorbidity., Methods: Fifty-three patients with LPR and 25 healthy controls were enrolled in this masked randomized controlled study. Fifteen naive patients with LPR were treated with magnesium alginate eye drops and oral therapy (magnesium alginate and simethicone tablets) with a 1-month follow-up. Clinical ocular surface evaluation, Ocular Surface Disease Index questionnaire, tear sampling, and conjunctival imprints were performed. Tear pepsin levels were quantified by ELISA. Imprints were processed for human leukocyte antigen-DR isotype (HLA-DR) immunodetection and for HLA-DR, IL8, mucin 5AC (MUC5AC), nicotine adenine dinucleotide phosphate (NADPH), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) transcript expression (PCR)., Results: Patients with LPR had significantly increased Ocular Surface Disease Index ( P < 0.05), reduced T-BUT ( P < 0.05), and higher meibomian gland dysfunction ( P < 0.001) compared with controls. After treatment, tear break-up time (T-BUT) and meibomian gland dysfunction scores improved to normal values. Pepsin concentration increased in patients with EGERD ( P = 0.01) and decreased with topical treatment ( P = 0.0025), significantly. HLA-DR, IL8, and NADPH transcripts were significantly increased in the untreated versus controls and comparable significant values were obtained after treatment ( P < 0.05). MUC5AC expression significantly increased with treatment ( P = 0.005). VIP transcripts were significantly higher in EGERD than in controls and decreased with the topical treatment ( P < 0.05). No significant changes were observed in NPY., Conclusions: We report an increase in prevalence of ocular discomfort in patients with GERD/LPR. The observations of VIP and NPY transcripts demonstrate the potential neurogenic nature of the inflammatory state. Restoration of the ocular surface parameters suggests the potential usefulness of topical alginate therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca 2+ and Zn 2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo . The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.

Raft-forming systems are designed to relieve reflux symptoms by forming a physical barrier on top of the stomach. The present study aimed to evaluate the physico-chemical properties of alginate-aloe vera raft-forming systems for the first time. To achieve this goal, aloe vera was used in the proportion of 1 and 1.5 % in raft suspensions containing 5 % alginate as the main component of gel structure. Rafts were characterized by their volume, floating behavior, thickness, swelling properties, strength, resilience, reflux resistance, and acid neutralization capacity (ANC). Results showed the effectiveness of aloe vera in forming rafts that were voluminous, buoyant with greater total floating time (TFT), and stronger than formulations with no aloe vera. Furthermore, data showed that the presence of aloe vera could improve resilience time, swelling proportions, resistance to reflux under simulant conditions of movement in the stomach, and ANC values of rafts. Rafts were further characterized by oscillatory strain sweep test, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Evaluation of the mechanical properties of rafts displayed a viscoelastic behavior of gels corresponding to the internal cross-linked structure of rafts. This study demonstrated that designing of alginate-aloe vera rafts can be suitable for the treatment of gastro-esophageal reflux disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The research aimed to develop novel bioadhesive sodium alginate (Na-Alg) microspheres laden pessaries for intravaginal delivery of tenofovir disoproxil fumarate (TDF), to overcome limitations of conventional dosage forms. Twelve batches of microspheres formulated by emulsification gelation method indicated that drug-polymer ratios and polymer type affected particle size, drug release, and entrapment efficiency (%EE). Microspheres of batch EH-8 with drug: polymer ratio of 1:4 containing equal amounts of Na-Alg and HPMC K100M displayed optimal %EE (62.09 ± 1.34 %) and controlled drug release (97.02 ± 4.54 % in 12 h). Particle size analysis in Matersizer indicated that microspheres (EH-8) displayed a surface-mean diameter of 11.06 ± 0.18 μm. Ex-vivo mucoadhesion studies on rabbit mucosa indicated that microspheres (EH-8) adhered well for 12 h. Microspheres integrated into pessaries displayed a sustained release profile (95.31 ± 1.37 % in 12 h) in simulated vaginal fluid. In vivo studies in rabbits indicated that pessaries displayed a significantly higher C max (41.18 ± 3.57 ng/mL) (P < 0.005) and reduced T max (1.00 ± 0.01 h) (P < 0.0001) of TDF concentrations in vaginal fluid compared to oral tablets. The microparticulate pessaries with the ability to elicit higher vaginal fluid levels in the crucial initial hours of insertion demonstrates a potential novel platform to offer better self-protection to HIV-negative women against HIV during sexual intercourse., Competing Interests: Declaration of competing interest There are no conflicts of interest related to the work undertaken., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia., (© 2024. The Author(s).)

Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats' testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation., (© 2024. The Author(s).)

Wounds were considered as defects in the tissues of the human skin and wound healing is said to be a tedious process as there are possibilities of infection or inflammation due to microorganisms. Modern moisture-retentive wound dressing (MMRWD) is opening a new window toward wound therapy. It comprises different types of wound dressing that has classified based on their functionality. Selective polysaccharide-polypeptide fiber composite materials such as hydrogels, hydrocolloids, hydro fibers, transparent-film dressing, and alginate dressing are discussed in this review as a type of MMRWD. The highlight of this polysaccharide and polypeptide based MMRWD is that it supports and enhances the healing of different types of wounds by moisture absorption thus preventing infection. This study has given enlightenment on the application of selected polysaccharide and polypeptide based MMRWD that enhances wound healing actions still it has been observed that the composite wound healing dressing is more effective than the single one. The nano-sized materials (synthetic nano drugs and phyto drugs) were found to increase the efficiency of healing action while coated in the wound dressing material. Future research is required to find out more possibilities of the different composite types of wound dressing in the healing action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca 2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1β and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment., (© 2023 Wiley Periodicals LLC.)

Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60-80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Skin is the largest organ of the human body, which acts as a protective barrier against pathogens. Therefore, a lot of research has been carried out on wound care and healing. Creating an ideal environment for wound healing and optimizing the local and systemic conditions of the patient play critical roles in successful wound care. Many products have been developed for improving the wound environment and providing a protected and moist area for fast healing. However, there is still high demand for new systems with high efficiency. The first generation of wound dressings merely covered the wound, while the subsequent/last generations covered it and aided in healing it in different ways. In modern wound dressings, the kind of used materials and their complexity play a crucial role in the healing process. These new systems support wound healing by lowering inflammation, exudate, slough, and bacteria. This study addresses a review of alginate/hyaluronic acid-based wound dressings developed so far as well as binary and ternary systems and their role in wound healing. Our review corroborates that these systems can open up a new horizon for wounds that do not respond to usual treatments and have a long curing period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The demand for nonbiological hemostatic materials has increased in surgical practice; however, few have sufficient hemostatic efficacy. This study investigated whether optimizing the composition of sodium calcium alginate, which forms a stable gel, improves hemostatic efficacy., Methods: The sodium calcium alginate was changed for each composition, including powder size, calcium substitution rate, molecular weight, and mannuronic/guluronic acid ratio. The hemostasis in liver punch-out injury and bleeding was evaluated using swine. For the study, sodium calcium alginate with different compositions was randomly applied to bleeding sites. Previous hemostatic materials, including cellulose and sodium alginate, were used as a control. We investigated hemostasis at 2 and 5 minutes after application., Results: Each powder size (53-150 μm, 150-250 μm, 53-250 μm) had a similar hemostatic effect. However, the hemostatic rate was significantly higher in sodium calcium alginate than in previous hemostatic materials (P value < .01). A 74.1% calcium substitution rate had the highest hemostasis at 2 and 5 minutes after application (2 minutes: 100%, 5 minutes: 95.2%). Regarding molecular weight, the hemostatic rate was significantly higher in 333,000 than in 50,000 (2 minutes: 95% vs 70%, 5 minutes: 95% vs 70%, P = .038). Moreover, a 1.9 mannuronic/guluronic acid ratio had the highest hemostasis compared with the 0.4 mannuronic/guluronic acid ratio (2 minutes: 58.8% vs 11.8%, 5 minutes: 58.8% vs 0%, P = .033) CONCLUSION: The composition of sodium calcium alginate with a high hemostatic effect was optimized. This new hemostatic material demonstrated potential usefulness for bleeding during surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hepatic fibrosis (HF) is a challenging clinical problem. Both sodium alginate (SA) and oxymatrine (OM) can be used to treat HF; however, the influence of viscosity on the therapeutic efficacy of sodium alginate is currently unknown. This study used a CCl 4 -induced HF mouse model to screen the specifications and doses of SA and investigate its therapeutic effects on HF in combination with OM. Sodium alginate of different viscosities ameliorated HF in mice, with 232 mPa·s SA delivered at a dose of 100 mg/kg showing remarkable therapeutic effect, characterized by reduced aspartate transaminase/alanine transaminase levels, reduced expression of α-SMA, collagen I, and other related genes, and increased abundance of beneficial intestinal probiotics such as Lactococcus and Blautia. The combination treatment further improved other related indices and increased the abundance of Phascolarctobacterium and Oscillospiraceae. These results suggest that the oral administration of SA may improve HF via the "gut-liver axis" based on the gut microbiota and has potential clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The effects of nanosized boron phosphate-filled sodium alginate composite gel (SA/BP) on the biological characteristics of three types of glioblastoma multiforme (GBM) cells (C6, U87MG and T98G) were examined in this study. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to determine the cytotoxicity of the composite gel on GBM, which was then compared to L929 healthy cells. Furthermore, wound healing, apoptosis, and colony formation capacities were evaluated. The investigation revealed that the SA/BP composite gel was successful in all GBM cells and could be used as a treatment agent for GBM and/or other invasive cancer types., Methods and Results: According to the results, the SA/BP composite gel had no effect on healthy fibroblast cells but had a lethal effect on all glioblastoma cells. Additionally, the wound healing method was used to examine the effect of the SA/BP composite gel on cell migration. It was discovered that the wound closed in 24 h in untreated control group cells, while the SA/BP composite gel closed up to 29.62%, 26.77% and 11.31% of the wound for C6, U87MG and T98G cell lines respectively. SA/BP significantly reduced cell migration in cancer cells. The effect of the generated SA/BP composite gel on cell colony development was assessed using a colony formation assay, and the cells reduced colony formation for all GBMs. It was roughly 45% for 24 h and 30% for 48 h when compared to the control group for C6 cells, 33%(24 h) and 40%(48 h) for U87MG cells, 40%(24 h) and 43%(48 h) for T98G cells. DAPI(4',6-Diamidino-2-phenylindole) and JC-1(5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine, iodide) staining to evaluate apoptosis revealed that the SA/BP composite gel dramatically enhanced the frequency of all GBMs undergoing apoptosis., Conclusions: In line with experimental findings, it was observed that the SA/BP composite gel system did not affect healthy fibroblast cells but had a cytotoxic effect on glioblastoma cells, significantly reduced cell migration and colony-forming capacity of cells, and significantly increased apoptosis and depolarization of cell membranes. Based on all these findings, it can be said that SA/BP composite gel has cytotoxic, antiproliferative and antiapoptotic effects on different glioblastoma cells., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

Background: Silica gel fiber (SGF) dressing is a novel patch for wound healing., Objective: To compare the efficacy and safety of SGF dressing with alginate dressing in local treatment of venous leg ulcers., Methods: Patients with venous leg ulcers who had undergone effective treatment of venous hypertension and debridement were randomized to receive wound care with either SGF dressing or alginate dressing for 4 weeks. Wounds were assessed weekly during the first 4 weeks and then every 2 weeks until the 8th week. The primary endpoint was the efficacy rate. Secondary endpoints included ulcer area reduction rate, healing rate, frequency of dressing changes, pain score, patient satisfaction, and treatment-related adverse events., Results: A total of 130 patients were enrolled, 67 treated with SGF and 63 with alginate dressing, and the efficacy rates were 89.6% (SGF group) and 84.1% (alginate group). SGF induced a higher "no pain" rate than alginate at week 2 (61.4% vs 43.5%) and week 3 (67.6% vs 53.1%), and a higher "highly satisfied" rate at week 4 (83.3% vs 78.8%) and week 8 (75% vs 59.1%). Markedly fewer dressing changes were required in the SGF group., Conclusions: SGF dressing is non-inferior to alginate dressing in treating venous leg ulcers. It even substantially decreased the frequency of dressing changes when compared with alginate dressing.

Partial-thickness thermal burn wounds are characterized by a prolonged inflammatory response, oxidative stress, tissue damage, and secondary necrosis. An optimal dressing for burn wounds would reduce inflammation and oxidative stress while providing a moist, absorbent, and protective cover. We have developed an extract from unfertilized salmon roe containing components with potential anti-inflammatory and antioxidative properties, called HTX. HTX has been combined with alginate from brown algae and nanocellulose from tunicates, and 3D printed into a solid hydrogel wound dressing called Collex. Here, Collex was tested on partial thickness burn wounds in Göttingen minipigs compared to Jelonet, and a variant of Collex without HTX. We found that dermal treatment of burn wounds with Collex resulted in accelerated healing at a majority of measured points over 23 days, compared to treatment with Jelonet. In comparison to Collex without HTX, Collex enhanced healing in the first week after trauma where wound progression was pronounced. Notably, Collex reduced the inflammatory response in the early post-injury phase. The anti-inflammatory response of Collex was investigated in more detail on activated M1 macrophages. We found that Collex, as well as HTX alone, significantly reduced the secretion of pro-inflammatory interleukin-1β as well as intracellular levels of oxidative stress. The results from this study indicate that Collex is a potent dressing for the treatment of burn wounds, with the anti-inflammatory effect of HTX beneficial in the initial phase, and the moist qualities of the hydrogel favorable both in the initial and the proceeding proliferative phase of wound healing., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association.)

Objective: The aim of this study was to compare Biatain Ag and Biatain Alginate Ag (both Coloplast, Denmark) as skin graft donor site dressings., Method: A single-centre, prospective, randomised clinical study was conducted. In patients who had undergone a skin graft operation, adjacent split-thickness skin graft donor sites were dressed with Biatain Ag and Biatain Alginate Ag, respectively. The primary outcomes were time to re-epithelialisation and pain score after the operation. The secondary outcomes were scar scores of the donor site after the operation, haematoma rates, infection rates, and exudation rates before wound healing. Results were compared using the Wilcoxon test and the Chi-squared test., Results: A total of 16 paired wounds in 16 patients were studied. The donor sites dressed with Biatain Ag needed more time for >90% re-epithelialisation than those dressed with Biatain Alginate Ag. On day 3 postoperatively, the pain scores with Biatain Ag were significantly less severe than those with Biatain Alginate Ag. On days 6, 9 and 12, the pain scores of both dressings did not differ significantly. The scar scores of the donor site dressed with Biatain Ag were significantly worse than those dressed with Biatain Alginate Ag at 6 months. With respect to infection rates, no significant differences were detected between these two groups. However, the exudation rates of the donor site dressed with Biatain Ag were significantly lower than those dressed with Biatain Alginate Ag., Conclusion: As skin graft donor site dressings, both Biatain Ag and Biatain Alginate Ag have advantages., Competing Interests: Declaration of interest: This clinical research was funded by the Social Development Guiding Project of Zhenjiang Science and Technology Planning (FZ2022090). The authors have no conflicts of interest to declare.

Chronic wounds induced by bacterial infection have seriously affected the health of people in the world. So, it is meaningful to develop a novel strategy with real-time infection monitoring and excellent antibacterial performance for enhancing wound management. Herein, we constructed a composite hydrogel by loading the pH indicator bromothymol blue (BTB) and gold nanocages containing 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (Au NCs@AIPH) into a polyacrylamide- co -poly(acrylic anhydride-modified oxidized sodium alginate) (PAM- co -PAOSA) hydrogel. In vitro and in vivo experimental results demonstrated that the composite hydrogel could effectively detect bacteria and diagnose the infection status of a wound in real time by showing visible color changes. In addition, the composite hydrogel containing Au NCs@AIPH possessed an excellent photothermal effect under near-IR (NIR) laser irradiation. The photothermal effect further activated AIPH to generate toxic free radicals to form combined antibacterial therapy for accelerating wound healing. Moreover, the composite hydrogel showed great biocompatibility. Therefore, the multifunctional hydrogel provided a novel wound management strategy for bacterial infection diagnosis and combined therapy in an infected wound.

Background: Donor site wounds of split-thickness skin grafts can be a major cause of morbidity. Choosing the appropriate dressing for these wounds is crucial to successful healing. Various types of dressing are available, including hydrogel dressings. A review of current evidence is required to guide clinical decision-making on the choice of dressing for the treatment of donor sites of split-thickness skin grafts., Objectives: To assess the effects of hydrogel dressings on donor site wounds following split-thickness skin grafts for wound healing., Search Methods: In July 2022 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL EBSCO Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting., Selection Criteria: Randomised controlled trials (RCTs) comparing hydrogel dressings with other types of dressing, topical treatments or no dressing, or with different types of hydrogel dressings in managing donor site wounds irrespective of language and publication status., Data Collection and Analysis: Two review authors independently carried out data extraction, risk of bias assessment using the Cochrane risk of bias tool, RoB 1, and quality assessment according to GRADE methodology., Main Results: We included two studies (162 participants) in this review. One study with three arms and 101 participants (15 months' duration) was conducted in a children's hospital, and compared hydrogel dressings in the form of Sorbact with Algisite, an alginate dressing and Cuticerin, a smooth acetate gauze impregnated with water-repellent ointment. Another study with two arms and 61 participants (19 months' duration) was conducted in three surgery departments and compared an octenidine-containing hydrogel dressing with an identical non-antimicrobial hydrogel dressing. We identified no studies that compared hydrogel dressings with another therapy such as a topical agent (a topical agent is a cream, an ointment or a solution that is applied directly to the wound), or no dressing, or a combination of hydrogel dressings and another therapy versus another therapy alone. Both studies were at high risk of attrition bias and the second study was also at unclear risk of selection bias. Amorphous hydrogel dressings versus other types of dressings Amorphous hydrogel dressings may increase time to wound healing when compared with alginate (mean difference (MD) 1.67 days, 95% confidence interval (CI) 0.56 to 2.78; 1 study, 69 participants; low-certainty evidence) or Cuticerin dressings (MD 1.67 days, 95% CI 0.55 to 2.79; 1 study, 68 participants; low-certainty evidence). The effect of amorphous hydrogel dressings compared with other types of dressings is uncertain for pain at the donor site and wound complications, including scarring and itching (very low-certainty evidence). No adverse events were reported in any of the groups. The study did not report health-related quality of life or wound infection. Octenidine-based hydrogel dressing versus octenidine-free hydrogel dressing The effect of octenidine-based hydrogel dressings versus octenidine-free hydrogel dressings is uncertain for time to wound healing (MD 0.40, 95% CI 0.28 to 0.52; 1 study, 41 participants) and wound infection, as the certainty of the evidence is very low. The certainty of the evidence is also very low for adverse events, with two participants in the intervention group and one participant in the comparison group reporting adverse events (risk ratio (RR) 0.58, 95% CI 0.06 to 5.89; 1 study, 41 participants). The study did not report donor site pain, health-related quality of life, or wound complications., Authors' Conclusions: There is insufficient evidence to determine the effect of hydrogel dressings on donor site wounds of split thickness skin grafts compared with other types of dressings. There is a need for adequately powered and well-designed RCTs, with adequate sample sizes, types of populations and subgroups, types of interventions, and outcomes, that compare hydrogel dressings with other treatment options in the treatment of donor site wounds of split-thickness skin grafts., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The gut microbiota are prominent in preserving intestinal environmental homeostasis and managing human health, and their dysbiosis has been directly related to many kinds of intestinal diseases. Probiotics-based therapy appears as a promising approach for the treatment of gut microbiota dysbiosis, while it always suffers from limited bioavailability and therapeutic effect after oral administration. Herein, we presented a facile and safe strategy to treat colitis by nanoencapsulation of probiotics and an anti-inflammatory agent, 5-aminosalicylic acid (5-ASA), within the gastrointestinal microenvironment responsive alginate polysaccharide. Because of acid resistance, the alginate-based coating protected probiotics from the harsh gastric condition. The coating could be disintegrated to release probiotics and 5-ASA upon arriving in the intestinal tract, where the pH is normally higher than 5. In the dextran sulfate sodium-induced colitis mouse model, probiotics recovered their bioactivities and acted together with anti-inflammatory 5-ASA to alleviate colitis by upregulating microbiota richness and diversity, reducing expression of proinflammatory cytokines, and restoring intestinal barriers. This work demonstrated the synergistic therapy of intestinal diseases based on alginate-encapsulated probiotics and a clinical drug, which provided an extensive method to improve the therapeutic effect of oral microecologics.

Aims: Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury., Methods: A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm 2 ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations., Results: No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80)., Conclusion: This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells., Competing Interests: None declared., (© 2023 Authors et al.)

Inflammatory bowel disease (IBD) is an inflammatory disorder that affects the gastrointestinal tract. IBD has become an increasingly common condition in both developed and developing nations over the last few decades, owing to a variety of factors like a rising population and diets packed with processed and junk foods. While the root pathophysiology of IBD is unknown, treatments are focused on medications aimed to mitigate symptoms. Alginate (AG), a marine-derived polysaccharide, is extensively studied for its biocompatibility, pH sensitivity, and crosslinking nature. This polymer is thoroughly researched in drug delivery systems for IBD treatment, as it is naturally available, non-toxic, cost effective, and can be easily and safely cross-linked with other polymers to form an interconnected network, which helps in controlling the release of drugs over an extended period. There are various types of drug delivery systems developed from AG to deliver therapeutic agents; among them, nanotechnology-based systems and hydrogels are popular due to their ability to facilitate targeted drug delivery, reduce dosage, and increase the therapeutic efficiency. AG-based carrier systems are not only used for the sustained release of drug, but also used in the delivery of siRNA, interleukins, and stem cells for site directed drug delivery and tissue regenerating ability respectively. This review is focussed on pathogenesis and currently studied medications for IBD, AG-based drug delivery systems and their properties for the alleviation of IBD. Moreover, future challenges are also be discoursed to improve the research of AG in the field of biopharmaceuticals and drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Biofilms play a role in recalcitrance and treatability of bacterial infections, but majority of known antibiotic resistance mechanisms are biofilm-independent. Biofilms of Pseudomonas aeruginosa, especially in cystic fibrosis patients infected with the alginate producing strains in their lungs, are hard to treat. Changes in growth-related bacterial metabolism in biofilm affect their antibiotic recalcitrance which could be considered for new therapies designed based on these changes. In this study, effects of nitrate, arginine, and ferrous were investigated on antibiotic recalcitrance in alginate-encapsulated P. aeruginosa strains isolated from cystic fibrosis patients in the presence of amikacin, tobramycin, and ciprofloxacin. Also, expression of an efflux pump gene, mexY, was analyzed in selected strains in the presence of amikacin and ferrous., Methods: Clinical P. aeruginosa strains were isolated from cystic fibrosis patients and minimum inhibitory concentration of amikacin, tobramycin, and ciprofloxacin was determined against all the strains. For each antibiotic, a susceptible and a resistant or an intermediate-resistant strain were selected, encapsulated into alginate beads, and subjected to minimal biofilm eradication concentration (MBEC) test. After determining MBECs, sub-MBEC concentrations (antibiotics at concentrations one level below the determined MBEC) for each antibiotic were selected and used to study the effects of nitrate, arginine, and ferrous on antibiotic recalcitrance of encapsulated strains. Effects of ferrous and amikacin on expression of the efflux pump gene, mexY, was studied on amikacin sensitive and intermediate-resistant strains. One-way ANOVA and t test were used as the statistical tests., Results: According to the results, the supplements had a dose-related effect on decreasing the number of viable cells; maximal effect was noted with ferrous, as ferrous supplementation significantly increased biofilm susceptibility to both ciprofloxacin and amikacin in all strains, and to tobramycin in a resistant strain. Also, treating an amikacin-intermediate strain with amikacin increased the expression of mexY gene, which has a role in P. aeruginosa antibiotic recalcitrance, while treating the same strain with ferrous and amikacin significantly decreased the expression of mexY gene, which was a promising result., Conclusions: Our results support the possibility of using ferrous and arginine as an adjuvant to enhance the efficacy of conventional antimicrobial therapy of P. aeruginosa infections., (© 2023. The Author(s).)

Alginate oligosaccharides (AOS) are divided by their monomer sequences into three types: oligomannuronate (MAOS), oligoguluronate (GAOS), and heterogeneous AOS (HAOS). However, how these AOS structures differentially regulate health and modulate gut microbiota is unclear. We explored the structure-function relationship of AOS both in an in vivo colitis model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged cell model. We found that MAOS administration significantly alleviated the symptom of experimental colitis and improved the gut barrier function in vivo and in vivo. Nevertheless, HAOS and GAOS were less effective than MAOS. The abundance and diversity of gut microbiota are obviously increased by MAOS intervention, but not by HAOS or GAOS. Importantly, microbiota from MAOS-dosed mice through FMT decreased the disease index level, alleviated histopathological changes, and improved gut barrier function in the colitis model. Super FMT donors induced by MAOS but not by HAOS or GAOS, seemed to exert potential in colitis bacteriotherapy. These findings may aid in establishing precise pharmaceutical applications based on the targeted production of AOS., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro . Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.

Calcium alginate dressings are commonly used on split-thickness skin donor sites, where they are typically removed after 14 days. Alginates have been used previously on superficial, partial thickness burns, but changed every 3 to 5 days. In this study, alginates were applied to superficial, partial thickness burns on adults within 36 hours of injury, then left intact for up to 14 days. Wound healing (≥95% wound epithelialization) and pain were measured. Twenty-one burns were reviewed on ten patients. Per the initial protocol, six patients were reviewed every 3 to 5 days, with removal of only secondary dressings, until days 13 to 14, when the alginate dressings were removed. One patient was reviewed every 3 to 5 days until day 10, when a clinic nurse removed the alginate dressing. Restrictions on movement during the COVID pandemic necessitated a protocol change, with only one review at approximately day 14 for removal of alginate and secondary dressings; three patients were reviewed in this manner. Burns on all patients were 100% epithelialized at the time of final review and there were no complications, such as scarring, infection, or need for grafting. Following initial debridement and dressings, patients reported minimal pain. Dressing costs appeared to be significantly decreased. This protocol may be particularly useful for patients managed in rural and remote locations, with telemedicine support if required., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications., Competing Interests: Declaration of competing interest The authors declare no competing and conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Intervertebral disc (IVD) degeneration is a major cause of low back pain and disability, affecting millions of people worldwide. Current treatments for IVD degeneration are limited to invasive surgery or pain management. Recently, there has been increasing interest in the use of biomaterials, such as alginate hydrogels, for the treatment of IVD degeneration. Alginate hydrogels are an example of such a biomaterial that is biocompatible and can be tailored to mimic the native extracellular matrix of the IVD. Derived from alginate, a naturally derived polysaccharide from brown seaweed that can be transformed into a gelatinous solution, alginate hydrogels are emerging in the field of tissue engineering. They can be used to deliver therapeutic agents, such as growth factors or cells, to the site of injury, providing a localized and sustained release that may enhance treatment outcomes. This paper provides an overview on the use of alginate hydrogels for the treatment of IVD degeneration. We discuss the properties of alginate hydrogels and their potential applications for IVD regeneration, including the mechanism against IVD degeneration. We also highlight the research outcomes to date along with the challenges and limitations of using alginate hydrogels for IVD regeneration, including their mechanical properties, biocompatibility, and surgical compatibility. Overall, this review paper aims to provide a comprehensive overview of the current research on alginate hydrogels for IVD degeneration and to identify future directions for research in this area., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Reflux asthma is an entity characterized by typical symptoms and, in some cases, is "silent"; it is more dangerous when associated with obesity and sleep apnea syndrome. Numerous studies demonstrate its high prevalence in the general population, particularly in the pediatric population, where, despite medical specialists' treatment, asthma symptoms remain poorly controlled with a high risk of acute exacerbations. This clinical study aims to show how the addition of a particular type of alginate (Deflux Plus sachets) containing hyaluronic acid and melatonin at low doses administered over a prolonged period of 6 months causes a reduction in vagal reflex stimulation of the esophagus and pulmonary microaspiration reflexes by regulating lower esophageal sphincter motility in asthmatic patients, improving the asthma control test (ATC) score. In the reported statistical analysis, receiver operating characteristic curves were performed for sensitivity and specificity for the analyzed parameters, including the ACT score, with statistically significant data p<0.0001. We conclude that combining conventional therapy for reflux asthma with alginates may improve the risk of acute asthma exacerbations and dynamic lung volumes.

To develop a new more efficient colon cancer treatment bio-vehicle, in frontier research, for the first time, an attempt has been made to design a unique colon-targeted bio-carrier containing polysaccharides along with nanoporous materials. So, at first, an imine-based covalent organic framework (COF-OH) with respectively an average pore diameter and surface area at 8.5058 nm and 208.29 m 2 ·g -1 was fabricated. In the next step, about 41.68 % and 95.8 % of 5-fluorouracil (5-Fu) and curcumin (CUR) respectively were loaded on COF-OH, and 5-Fu + CUR@COF-OH was achieved. Due to the higher rate of drug releases in simulated stomach media, 5-Fu + CUR@COF-OH was coated with a mixture of alginate (Alg) and carboxymethyl starch (CMS) via the ionic crosslinking (Alg/CMS@(5-Fu + CUR@COF-OH)). Findings displayed that the use of polysaccharide coat reduce the drug releases in simulated gastric and improved it in simulated intestinal and colonic fluids. The beads swelled about 93.33 % under simulated gastrointestinal conditions, but this value was found higher in the simulated colonic environment and reached 326.67 %. The hemolysis rate lower than 5 %, as well as the cell viability higher than 80 %, were the main showing signs of system biocompatibility. Altogether, the results of the preliminary investigations can highlight the potential of the Alg/CMS@(5-Fu + CUR@COF-OH) for colon-specific drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Chronic refractory wounds are a common complication in diabetic patients. Adipose-derived mesenchymal stem cells (ASCs) have been shown to play an essential role in diabetic wound repair., Aims: To determine whether a composite of ASCs and sodium alginate/gelatin (Gel-Al) hydrogel can promote diabetic wound healing., Methods: Full-thickness cutaneous wounds were created in streptozotocin-induced diabetic rats prior to treatment with Gel-Al hydrogels loaded with ASCs. Hydrogel biocompatibility and wound healing were analyzed. Hematoxylin and eosin staining, Masson staining, immunofluorescence, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time PCR were performed for the assessment of cellular responses., Results: Compared to the control group or Gel-Al alone group, the combination of Gel-Al and ASCs promoted wound closure, facilitated granulation tissue regeneration and collagen deposition, and upregulated the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and endothelial cell marker CD31. Moreover, the combination of Gel-Al and ASCs decreased interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression, increased transforming growth factor beta1 (TGFβ1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-13 (IL-13) expression, and increased M2 macrophage polarization., Conclusions: Gel-Al hydrogels loaded with ASCs accelerate diabetic wound healing. The Gel-Al hydrogel-based ASC system therefore represents an innovative therapeutic strategy for diabetic wound repair., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Intramyocardial injection of hydrogels possesses great potential in the minimally invasive treatment of myocardial infarction (MI), but the current injectable hydrogels lack conductivity, long-term angiogenesis inductive ability, and reactive oxygen species (ROS)-scavenging ability, which are essential for myocardium repair. In this study, lignosulfonate-doped polyaniline (PANI/LS) nanorods and adeno-associated virus encoding vascular endothelial growth factor (AAV9-VEGF) are incorporated in the calcium-crosslinked alginate hydrogel to develop an injectable conductive hydrogel with excellent antioxidative and angiogenic ability (Alg-P-AAV hydrogel). Due to the special nanorod morphology, a conductive network is constructed in the hydrogel with the conductivity matching the native myocardium for excitation conduction. The PANI/LS nanorod network may also have large specific surfaces and effectively scavenges ROS to protect cardiomyocytes from oxidative stress damage. AAV9-VEGF transfects the surrounding cardiomyocytes for continuously expressing VEGF, which significantly promotes the proliferation, migration and tube formation of endothelial cells. After injecting the Alg-P-AAV hydrogel around the MI area in rats, the generation of gap junctions and angiogenesis are greatly improved with reduced infarct area and recovered cardiac function. The remarkable therapeutic effect indicates the promising potential of this multi-functional hydrogel for MI treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Epithelial barrier dysfunction is a hallmark of gastroesophageal reflux disease (GERD) related to symptom origination, inflammatory remodeling and carcinogenesis. Alginate-based antireflux medications were previously shown to topically protect against peptic barrier disruption, yet the molecular mechanisms of injury and protection were unclear. Herein, Barrett's esophageal (BAR-T) cells were pretreated with buffered saline (HBSS; control), dilute alginate medications (Gaviscon Advance or Gaviscon Double Action, Reckitt Benckiser), a viscosity-matched placebo, or ADAM10 and matrix metalloproteinase (MMP) inhibitors before exposure to HBSS pH7.4 or pH4 ± 1 mg/mL pepsin for 10-60 min. Cell viability was assessed by ATP assay; mediators of epithelial integrity, E-cadherin, ADAM10, and MMPs were examined by Western blot and qPCR. Alginate rescued peptic reduction of cell viability ( p < 0.0001). Pepsin-pH4 yielded E-cadherin fragments indicative of regulated intramembrane proteolysis (RIP) which was not rescued by inhibitors of known E-cadherin sheddases. Transcriptional targets of E-cadherin RIP fragments were elevated at 24 h ( MMP-1,2,9,14 ; p < 0.01). Alginate rescued E-cadherin cleavage, ADAM10 maturation, and MMP induction ( p < 0.01). Results support RIP as a novel mechanism of peptic injury during GERD. Alginate residue after wash-out to mimic physiologic esophageal clearance conferred lasting protection against pepsin-induced molecular mechanisms that may exacerbate GERD severity and promote carcinogenesis in the context of weakly acidic reflux.

Objectives: To develop alginate nanoparticles functionalized with polysorbate 80 (P80) as miltefosine carriers for brain targeting in the oral treatment of cryptococcal meningitis., Methods: Miltefosine-loaded alginate nanoparticles functionalized or not with P80 were produced by an emulsification/external gelation method and the physicochemical characteristics were determined. The haemolytic activity and cytotoxic and antifungal effects of nanoparticles were assessed in an in vitro model of the blood-brain barrier (BBB). A murine model of disseminated cryptococcosis was used for testing the efficacy of oral treatment with the nanoparticles. In addition, serum biomarkers were measured for toxicity evaluation and the nanoparticle biodistribution was analysed., Results: P80-functionalized nanoparticles had a mean size of ∼300 nm, a polydispersity index of ∼0.4 and zeta potential around -50 mV, and they promoted a sustained drug release. Both nanoparticles were effective in decreasing the infection process across the BBB model and reduced drug cytotoxicity and haemolysis. In in vivo cryptococcosis, the oral treatment with two doses of P80 nanoparticles reduced the fungal burden in the brain and lungs, while the non-functionalized nanoparticles reduced fungal amount only in the lungs, and the free miltefosine was not effective. In addition, the P80-functionalization improved the nanoparticle distribution in several organs, especially in the brain. Finally, treatment with nanoparticles did not cause any toxicity in animals., Conclusions: These results support the potential use of P80-functionalized alginate nanoparticles as miltefosine carriers for non-toxic and effective alternative oral treatment, enabling BBB translocation and reduction of fungal infection in the brain., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Today, with the salient advancements of modern and smart technologies related to tissue engineering and regenerative medicine (TE-RM), the use of sustainable and biodegradable materials with biocompatibility and cost-effective advantages have been investigated more than before. Alginate as a naturally occurring anionic polymer can be obtained from brown seaweed to develop a wide variety of composites for TE, drug delivery, wound healing, and cancer therapy. This sustainable and renewable biomaterial displays several fascinating properties such as high biocompatibility, low toxicity, cost-effectiveness, and mild gelation by inserting divalent cations (e.g., Ca 2+ ). In this context, challenges still exist in relation to the low solubility and high viscosity of high-molecular weight alginate, high density of intra- and inter-molecular hydrogen bonding, polyelectrolyte nature of the aqueous solution, and a lack of suitable organic solvents. Herein, TE-RM applications of alginate-based materials are deliberated, focusing on current trends, important challenges, and future prospects.

Bone augmentation has an enormous demand in oral clinical treatment. Although there are various options available for clinical management to address it, these approaches could increase patient suffering due to surgical trauma and even cause psychological trauma to the patients. Moreover, presently, there is still a lack of well-considered microinvasive bone augmentation systems to deal with this challenge. Herein, we newly developed a subperiosteal injectable and osteogenesis-promoting hydroxylapatite/laponite/alginate nanocomposite hydrogels to address the insufficient microinvasive bone augmentation strategies. The physical performances (like swelling profiles, degradation behaviors, mechanical properties, and surface morphologies) of the gels were determined, and can be slightly tuned through altering concentrations of laponite. The cytocompatibility test results show outstanding biocompatibility of the hydrogels. Furthermore, the in vitro testing for bone-inducing activity and in vivo determination of bone-augmentation in the rat cranial subperiosteum exhibit that the hydrogels significantly promoted rat periosteum-derived mesenchymal stromal cells (P-MSCs) osteogenic differentiation in vitro and bone augmentation in vivo. Therefore, the research reveals that the nanocomposite hydrogels possessing subperiosteal microinvasive injectability, osteogenesis-enhancing capability, and clinical applicability have extremely great potential application in subperiosteal microinvasive bone augmentation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)