Investigating the Role of Amino Acids in Short Peptides for Hydroxyapatite Binding and Osteogenic Differentiation of Mesenchymal Stem Cells to Aid Bone Regeneration.

Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs). We adopted a simplistic approach of rationally designing amphiphilic peptides by incorporating amino acids, Ser, pSer, Pro, Hyp, Asp, and Glu, which are present in either collagenous or noncollagenous proteins and render properties like antioxidant, calcification, and mineralization. A total of six tetrapeptides, Trp-Trp-His-Ser (WWHS), Trp-Trp-His-pSer (WWHJ), Trp-Trp-His-Pro (WWHP), Trp-Trp-His-Hyp (WWHO), Trp-Trp-His-Asp (WWHD), and Trp-Trp-His-Glu (WWHE), were synthesized. Four peptides were found to self-assemble into nanofibrillar gels resembling the extracellular matrix (ECM), and the remaining two peptides (WWHJ, WWHP) self-assembled into nanorods. The peptides showed excellent cell adhesion, encapsulation, proliferation, and migration and induced the differentiation of mesenchymal stem cells (MSCs), as evident from the enhanced mineralization, resulting from the upregulation of osteogenic markers, RUNX 2, COL I, OPN, and OCN, alkaline phosphatase (ALP) production, and calcium deposition. The peptides also induced the downregulation of inflammatory markers, TNF-α and iNOS, and the upregulation of the anti-inflammatory marker, IL-10, resulting in M2 macrophage polarization. RANKL and TRAP genes were downregulated in a coculture system of MC3T3-E1 and RAW 264.7 cells, implying that peptides promote osteogenesis and inhibit osteoclastogenesis. The peptide-based biomaterials developed in this work can enhance bone regeneration capacity and show strong potential as scaffolds for bone tissue engineering.

Thermoresponsive Gels with Embedded Starch Microspheres for Optimized Antibacterial and Hemostatic Properties.

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

Anti-inflammatory and wound healing effects of mouth gel containing kaempulchraol K from Kaempferia galanga rhizomes.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga L. is one of the important medicinal plants and has been used in Thailand for treating inflammation and wound. AIM OF THE STUDY: This study aimed to investigate the efficacy of the compound from K. galanga on wound healing and anti-inflammatory activities and develop a new product in gel form to maximize the benefits of this plant. MATERIALS AND METHOD: The mouth gel containing kaempulchraol K (KG2) was prepared by using 1.5% carbopol 934 as a gelling agent. Formulations of mouth gel containing KG2 at 0.10%, 0.25%, and 0.50% w/w were evaluated for color, smell, pH values, viscosity, and separation. Also, the chemical and biological stabilities of mouth gel containing KG2 were evaluated by heating-cooling test. The anti-inflammatory activity was tested against RAW 264.7 cells nitric oxide (NO) production and wound healing assay was performed using human gingival fibroblasts (HGF). RESULTS: Compound KG2 exhibited anti-NO production with an IC50 value of 66.8 µM and the wound healing activity of compound KG2 showed cell viability in the range of 90.9-111.4%. In addition, compound KG2 at a concentration of 3 µM induced the highest proportion of cell migration on day 3 at 90.2 ± 2.4%. The mouth gel containing KG2 both before and after the heating-cooling test exhibited good consistency, with pH values in the range of 6.64-6.71 (before) and 6.63-6.68 (after). Meanwhile, the viscosity was 81,700-96,700 cP (before) and 78,300-93,300 cP (after). For the chemical stability test of the active ingredient of mouth gel, the compound showed good stability after mixing with the gel base. The mouth gel exhibited anti-inflammation with IC50 values > 1000 µg/ml both before and after accelerating conditions. The wound healing activity of mouth gel containing KG2 (0.50% w/w) showed the highest % cell viability at 128.6% (before) and 123.8% (after). For cell migration, the result suggested that the mouth gel containing KG2 at 0.10%, 0.25%, and 0.50% w/w (3 µg/ml) on day 3 enhanced cell migration higher than that of the positive controls both before (85.0-96.8%) and after (and 84.4-94.3%) the accelerating conditions. CONCLUSION: The present study shows that mouth gel containing 0.50% KG2 is the most appropriate with good physical, chemical, and biological stabilities and might be one of the alternative sources for treatment of mouth ulcers (oral stomatitis) derived from aphthous ulcers, chemotherapy, and radiotherapy treatments.

Gelatin Methacryloyl Based Injectable Cryogels with Tunable Degradability for Cell Delivery.

Scaffold-based cell delivery can improve therapeutic effects of transplanted cells in cell therapy. Biomaterial scaffolds serveas niche for cell growth and proliferation which improves cell survival and overall function post cell delivery. In this study, gelatin methacryloyl based injectable scaffolds made using poly(ethylene)glycol as a sacrificial polymer and cryogelation as a technique, are demonstrated to have tunable degradability and porosity that is required for cell and drug delivery applications. The pore size (10-142 µm) of these gels makes them suitable for loading different cell types as per the application. In vitro studies using mammalian cells confirm that these cryogels are cytocompatible. These cell-laden scaffolds are injectable and have a cell retention ability of up to 90% after injection. Rheology is done to evaluate stiffness and shape recovery property, and it is found that these gels can maintain their original shape even after applying 7 cycles of strain from 0.1% to 20%. Furthermore, their degradability can be modulated between 6 and 10 days by changing the overall polymer composition. Thus, injectability and degradability of these cryogels can circumvent invasive surgical procedures, thereby making them useful for a variety of applications including delivery of cells and bioactive factors.

Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride.

OBJECTIVE: The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form. SIGNIFICANCE: Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability. METHOD: In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X1) as gelling agent and hydroxypropyl methyl cellulose K4M (X2) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization. RESULT: Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months. CONCLUSION: It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.

Intranasal administration of innovative triamcinolone acetonide encapsulated cubosomal in situ gel: formulation and characterization.

AIM: The primary objective of the research was to develop a cubosomal in situ gel encapsulated with Triamcinolone acetonide (TCA) in order to enhance its penetration through the blood-brain barrier (BBB) when administered via the intranasal route, thus enabling efficient and rapid action. METHOD: Cubosomes were formulated by top-down approach using glyceryl monooleate (GMO), using pluronics127 (PF127) and polyvinyl alcohol (PVA) in varying proportions based on the Box-Behnken design. High resolution transmission electron microscopy (HR-TEM) analysis confirmed the morphology of the cubosomes. The in situ gel was formulated and optimized. Experiments involving ex vivo permeation and histopathology analyses were undertaken to evaluate drug permeation and tissue effects. RESULTS: The cubosomes exhibited a particle size (PS) of 197.9 nm, zeta potential (ZP) of -31.11 mV, and entrapment efficacy (EE) of 84.31%, with low deviation. Batch F4 (19% PF127) showed favorable results. In vitro and ex vivo permeation studies revealed drug release of 78.59% and 76.65%, respectively, after 8 h. Drug release followed the Hixson Crowell model of release kinetics. The histopathological examination revealed no signs of toxicity or adverse effects on the nasal mucosa of the sheep. The formulation exhibited short-term stability, maintaining its integrity and properties when stored at room temperature. CONCLUSION: The utilization of an intranasal cubosomal in situ gel encapsulated with TCA was anticipated to lower intracranial pressure and improve patient adherence by offering effective relief for individuals suffering from Brain edema. This efficacy is attributed to its rapid onset of action and its safe and well-tolerated dosage form.

Novel Antibacterial and Biocompatible Nanostructured Gels Based on One-step Synthesis as a Potential Disinfectant for Endodontic Infection Control.

AIM: The objective of this study was to develop nanostructured gels as biocompatible intracanal disinfectants by one-step microwave radiation-assisted synthesis. METHODS: Polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as a support network, and polyethylene glycol (PEG) was used as a reducing agent. The gels were characterized by measuring the swelling ratio (SR) and rheological properties and by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The antibacterial effects of each gel were evaluated against the endodontic clinical strain Enterococcus faecalis. Then, the viability of the 21-day mature multispecies bacterial biofilm was assessed using confocal microscopy in an ex vivo model, where the biofilm was exposed to the mix of nanogels. The cell proliferation, viability, and morphology of human periodontal ligament (HPDL) cells were quantified using a real-time IncuCyte® S3 Live-Cell System. Viability was measured by confocal microscopy using an ex vivo model exposing a 21-day mature multispecies bacterial biofilm to the mix of nanogels. RESULTS: The antibacterial activity of the gels coincided with the superficial characterization and the solubility of the gel in the growth medium. Gels with higher viscosity (327.85-980.58 Pa s), higher dissolution (42-70%SR), and lower porosity (no porosity and 611.63 nm) showed excellent antibacterial activity against E. faecalis. Despite their physicochemical characteristics, CuNPs gels showed greater effectiveness against E. faecalis.These nanostructured gels with high PVA concentrations promote HPDL cells proliferation while still exerting antibacterial properties. Mix of nanogels showed an increase non-viable cells biomass from at of application. CONCLUSIONS: The use of biocompatible polymers influences the physicochemical, bactericidal, and cytotoxic response, making these materials potential disinfectant agents against resistant bacteria with good biocompatibility and improved HPDL cells proliferation.

Formulation and Evaluation of Herbal-Based Antiacne Gel Preparations.

Acne vulgaris is an inflammatory skin condition that affects virtually everyone at some point. Papules, comedones, pustules, scarring, and nodules are standard features of the disease and can have a detrimental social and psychological impact on an individual. Although allopathic acne treatments are available, they have adverse side effects, are expensive, and are prone to cause antibiotic resistance. The present study is aimed at formulating and evaluating topical gels containing Aloe vera, Allium cepa, and Eucalyptus globulus extracts as potential antiacne drugs. Six formulations containing the herbal extracts were prepared using 1% Carbopol 940 as a gelling agent. The phytochemical composition of the plant extracts was determined. The extracts and gels' minimum inhibitory concentration (MIC) was assessed using the microbroth dilution method. The physicochemical properties of the formulated gels, such as homogeneity, colour, texture, odour, grittiness, spreadability, extrudability, viscosity, pH, and drug content, were evaluated. All the plant extracts contained alkaloids, flavonoids, tannins, triterpenoids, and coumarins. The gel formulations showed varying activity against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa at various concentrations. The phytochemical components of the plant extracts are probably responsible for the antimicrobial activity of the gel formulations. The 5% Aloe vera-Allium cepa (1 : 1) combination gel formulation showed excellent activity against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with MICs of 12.50, 25.00, 6.25, 25.00, and 12.50 mg/mL, respectively. The gels generally had good physicochemical and antimicrobial properties and could be used as antiacne remedies.

Influence of bleaching gels formulated with nano-sized sodium trimetaphosphate and fluoride on the physicochemical, mechanical, and morphological properties of dental enamel.

OBJECTIVES: To evaluate in vitro the effects of sodium fluoride (F) and nano-sized sodium trimetaphosphate (TMPnano) added to a 35% hydrogen peroxide (H2O2) bleaching gel on the color alteration, enamel mechanical and morphological properties, and H2O2 transamelodentinal diffusion. MATERIALS AND METHODS: Bovine enamel/dentin discs (n = 180) were divided according to the bleaching gel: 35% H2O2 (HP); 35% H2O2 + 0.1% F (HP/F); 35% H2O2 + 1% TMPnano (HP/TMPnano); 35% H2O2 + 0.1% F + 1% TMPnano (HP/F/TMPnano) and 35% H2O2 + 2% calcium gluconate (HP/Ca). The gels were applied 3 times by 40 min; once each 7-day. The Commission Internationale de l'Eclairage (CIE) L*a*b* total color alteration (ΔE), color alteration by CIEDE2000 (ΔE00), whitening index (ΔWID), surface (SH) and cross-sectional hardness (ΔKHN), surface roughness (Ra), and transamelodentinal diffusion were determined. Enamel surfaces were evaluated by Scanning Electron Microscopy (SEM) and X-ray Dispersive Energy (EDX). Data were submitted to ANOVA, followed by the Student-Newman-Keuls test (p <0.05). RESULTS: ΔE, ΔE00, and ΔWID were similar among the gels that promoted a bleaching effect after treatment (p <0.001). Mineral loss (SH and ΔKHN), Ra, and H2O2 diffusion were lower for HP/F/TMPnano; the HP and HP/Ca groups presented the highest values (p <0.001). For SEM/EDX, surface changes were observed in all bleached groups, but less intense with TMPnano. CONCLUSIONS: Gels containing F/TMPnano do not interfere with the bleaching effect and reduce enamel demineralization, roughness, H2O2 diffusion, and morphological changes. CLINICAL RELEVANCE: Whitening gels containing F/TMPnano can be used as a new strategy to increase safety and maintain clinical performance.

Dentine tubule occlusion effect of hydrolyzed casein in a bioactive glass-based dental desensitizing gel.

OBJECTIVES: The effectiveness of three different groups of polyethylene glycol (PEG)-based gels containing powders on dentin hypersensitivity (DH) treatment were assessed and compared with Actimins® as commercial reference group. METHODS: Hydroxyapatite nanorods (nHA) and sol-gel-derived 45S5 bioglass (SGD 45S5) powders were synthesized through hydrothermal and sol-gel methods, respectively. First, 25 demineralized dentin disks were divided into five groups. Then, the prepared gels based on 45S5 bioglass with and without hydrolyzed casein (HC) as experimental, nHA gel and Actimins® as positive and commercial reference groups were applied twice a day on disks by a micro applicator. To mimic the oral environment, treated disks were immersed in artificial saliva in a water bath at 37 °C for 7 days. However, in the negative control group, no agent was applied on the samples. FE-SEM, EDS, AFM, and XRD were performed to assess tubule occlusion. One-way ANOVA test was used for statistical analysis and p*<0.05 was set as the significance level. RESULTS: The nHA with an average aspect ratio of 2.77 and the SGD 45S5 powders with a polygonal morphology and the average size of 48.64±11.38 µm were synthesized. After treatment, tubule occlusion in HC-SGD 45S5 and nHA gels were shown to be higher than other groups. The root mean square roughness (Rrms) of the above-mentioned gels showed to be 121.54±9.25 nm, and 312.6 ± 9 nm, respectively. CONCLUSION: The nHA containing group exhibited the highest tubule occlusion efficiency (i.e., tubule diameter of 0.92±0.32 µm) with a superior mineral precipitation. HC as a novel material demonstrates to be potentially beneficial in DH treatment. CLINICAL SIGNIFICANCE: DH as a common issue may be reduced or eliminated by occlusion of patent dentinal tubules. There are various types of desensitizing agents capable of controlling the DH by the occlusion of patent dentinal tubules. The desensitizing gels developed in this study showed to be promising for clinical and home-use applications.

A gel-forming α-MSH analog promotes lasting melanogenesis.

The α-MSH peptide plays a significant role in the regulation of pigmentation via the melanocortin 1 receptor (MC1R). It increases the DNA repair capacity of melanocytes and reduces the incidence of skin cancers. As such, α-MSH analogs could have the utility for protecting against UV-induced skin DNA damage in susceptible patients. Recently, α-MSH analogs have been approved for the treatment of erythropoietic protoporphyria, hypoactive sexual desire, or pediatric obesity. However, the delivery of these drugs requires inconvenient implants or frequent injections. We recently found that select palmitoylated melanocortin analogs such as afamelanotide and adrenocorticotropin peptides self-assemble to form liquid gels in situ. To explore the utility of these novel analogs, we studied their pharmacological characteristics in vitro and in vivo. Acylated afamelanotide (DDE 313) and ACTH1-24 (DDE314) analogs form liquid gels at 6-20% and have a significantly increased viscosity at >2.5% compared to original analogs. Using the DDE313 analog as a prototype, we showed gel-formation reduces the passage of DDE313 through Centricon filters, and subcutaneous injection of analog gel in rats leads to the sustained presence of the peptide in circulation for >12 days. In addition, DDE313 darkened the skin of frogs for >4 weeks, whereas those injected with an equivalent dose of afamelanotide lost the tanning response within a few days. Because self-assembled gels allow sustained activation of melanocortin receptors, further studies of these analogs may allow the development of effective and convenient tanning therapies to prophylactically protect against UV-induced malignant transformation of skin cells in susceptible patients.

Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects. METHODS: An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study. RESULTS: All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (Tmax) of 1.00 h, and mean values of the peak concentration (Cmax) and area under the concentration-time curve (AUC0-t) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam. CONCLUSION: Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study. CLINICAL TRIAL REGISTRATION: The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

Comparison of the effect of tea tree oil eye gel with standard treatment in patients with anterior blepharitis: An open-label clinical trial.

Purpose: Daily cleansing of eyelids is very important to carry out a successful blepharitis treatment. However, there are no therapeutic guidelines for blepharitis. The aim was to compare the symptomatic relief of anterior blepharitis using Blephamed eye gel, a cosmetic product, versus standard treatment. Methods: The study was a prospective, interventional open label clinical trial at a university-based hospital. The test population was subjects aged 18-65 years who presented with mild to moderate anterior blepharitis. Eyelid hygiene was applied twice a day. At each visit, a detailed assessment of symptomatology was carried out. A two-way repeated measure mixed model ANOVA was used to compare two groups by time. Results: In total, 61 patients with mean age of 60.08 ± 16.69 years were enrolled in the study including 30 patients in standard group and 31 patients in Blephamed group. Two groups did not differ in terms of age (P = 0.31) and eye laterality (P = 0.50). The baseline scores of erythema, edema, debris, and symptoms as well as total score were similar between two groups (all P values >0.50). Two groups became different for all these parameters at day 45 (all P values <0.001). Significant interaction was detected between time and intervention groups for all severity parameters of blepharitis as well as total score (all P values <0.001). Conclusion: Eyelid hygiene with Blephamed more significantly decreased symptoms of anterior blepharitis compared to standard treatment.

Collagen Gels Crosslinked by Photoactivation of Riboflavin for the Repair and Regeneration of Corneal Defects.

Bioengineered corneal tissue is a promising therapeutic modality for the treatment of corneal blindness as a substitute for cadaveric graft tissue. In this study, we fabricated a collagen gel using ultraviolet-A (UV-A) light and riboflavin as a photosensitizer (PhotoCol-RB) as an in situ-forming matrix to fill corneal wounds and create a cohesive interface between the crosslinked gel and adjacent collagen. The PhotoCol-RB gels supported corneal epithelialization and exhibited higher transparency compared to physically crosslinked collagen. We showed that different riboflavin concentrations yielded gels with different mechanical and biological properties. In vitro experiments using human corneal epithelial cells (hCECs) showed that hCECs are able to proliferate on the gel and express corneal cell markers such as cytokeratin 12 (CK12) and tight junctions (ZO-1). Using an ex vivo burst assay, we also showed that the PhotoCol-RB gels are able to seal corneal perforations. Ex vivo organ culture of the gels filling lamellar keratectomy wounds showed that the epithelium that regenerated over the PhotoCol-RB gels formed a multilayer compared to just a double layer for those that grew over physically cross-linked collagen. These gels can be formed either in situ directly on the wound site to conform to the geometry of a defect, or can be preformed and then applied to the corneal wound. Our results indicate that PhotoCol-RB gels merit further investigation as a way to stabilize and repair deep and perforating corneal wounds.

Beneficial Effect of Polysaccharide Gel Made of Xanthan Gum and Locust Bean Gum on Bovine Oocytes.

The present study examined the effect of polysaccharides gels made of xanthan gum and locust bean gum (gel culture system) on oocyte maturation and explored the molecules causing the beneficial effect of the gel culture system. Oocytes and cumulus cells complexes were collected from slaughterhouse-derived ovaries and cultured on a plastic plate or gel. The gel culture system improved the rate of development to the blastocyst stage. The oocytes that matured on the gel contained high lipid contents and F-actin formation, and the resultant 8-cell stage embryos had low DNA methylation levels compared to their plate counterparts. RNA sequencing of the oocytes and embryos revealed the differentially expressed genes between the gel and plate culture systems, and upstream regulator analysis revealed estradiol and TGFB1 as top activated upstream molecules. The medium of the gel culture system contained higher concentrations of estradiol and TGFB1 than that of the plate cultures system. Supplementation of the maturation medium with either estradiol or TGFB1 resulted in high lipid content in oocytes. In addition, TGFB1 improved the developmental ability of the oocytes and increased F-actin content while reducing DNA methylation levels in the 8-cell stage embryos. In conclusion, the gel culture system is useful for embryo production, potentially through the upregulation of TGFB1.

A self-gelling starch-based sponge for hemostasis.

Uncontrolled bleeding remains one of the direct causes of high mortality. There is an urgent need for developing emergency hemostats capable of coping with uncontrolled bleeding. The commercial starch-based hemostatic powder (PerClot®) requires compression during application, which limits its application in hemostasis of irregular and non-compressed wounds. Herein, a boronic acid-modified thiol starch sponge (St-SP sponge) with self-gelling properties was developed for hemorrhage control. The results show that the St-SP sponge could quickly absorb blood, self-gel and self-heal to seal the bleeding sites. In addition, the St-SP sponge can rapidly initiate the coagulation cascade and promote the adhesion and aggregation of erythrocytes and platelets. The St-SP sponge exhibited significantly improved in vitro and in vivo hemostatic abilities as compared with PerClot. Notably, the St-SP sponge attained complete hemostasis without any compression in 61.5 s and made a great difference compared to PerClot (169 s) for the irregular wound constructed on the rabbit liver. In addition, the St-SP sponge had good hemocompatibility and cytocompatibility. It turns out that the newly developed St-SP sponge is a promising material for first-aid hemostasis of irregular and non-compressed wounds.

Use of topical morphine gel in epidermolysis bullosa wounds-A series of case studies.

In recent years, the use of topical morphine gel has increased in the palliative care setting to reduce pain in chronic wounds and fungating tumours. However, there is a paucity of evidence to support its effectiveness. Epidermolysis bullosa (EB) is a rare genetic skin fragility disorder characterised by painful chronic wounds. Adequate control of wound pain can be challenging in this patient group due to other complexities associated with the more severe sub-types of the disease. Topical morphine gel has been used as an adjunct therapy in a small number of EB patients in our tertiary centre in an attempt to improve pain control and quality of life. The purpose of this paper is to demonstrate the efficacy of topical morphine gel used in a variety of EB wounds as well as patient reported reduction in pain through a series of case studies. The case studies suggest a positive effect of topical morphine gel on painful wounds across a spectrum of EB subtypes.

Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery: Pharmacodynamic and Safety Evaluation.

BACKGROUND: When administered transdermally, desonide is ineffective due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel. METHODS: Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate ® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure safety, atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay. RESULTS: Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of the ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase. CONCLUSION: Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides a higher transdermal potential than other delivery systems. In this study, it was found that nanoemulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has a significant curative effect on dermatitis/eczema in a mouse model and is expected to provide a new, efficient, and low toxic preparation for clinical treatment of dermatitis/eczema through the percutaneous system.

Biopolymer gels as components of protective medium for cryopreservation of spermatogonial stem cells.

Biopolymer gels attract a lot of attention in a field of biothechnology due to their excellent compatibility and degradation. Their application is also promising for cryopreservation of spermatogonial stem cells (SSCs) which is so necessary to preserve the fertility of young patients. The aim of the study was to determine the effectiveness of biopolymer gels as a component of cryopreservation medium for SSCs of immature rats at the stage of exposure to cryoprotectants. It was found that 30-min exposure to cryopreservation media based on collagen or fibrin gel with an addition of 5% Me2SO or 6% glycerol did not lead to significant changes in membrane integrity, cytochrome C content, metabolic, mitochondrial and antioxidant activities in SSCs compared to the control (Leibovitz-based cryomedium). But fibrin gel more than collagen reduced the toxic effects of Me2SO and glycerol on SSCs increasing exposure time up to 45 min without significant changes in cell viability. The same cryoprotectants in Leibovitz-based media showed significant toxicity starting from the 15th minute of exposure. Necrosis was the main cause of cell death at this stage of cryopreservation in all experimental groups. The obtained results can be used to optimize SSC cryopreservation protocols for further cell autotransplantation for spermatogenesis initiation in boys who undergo gonadotoxic therapy in prepubertal age.

Effect of highly concentrated bleaching gels on enamel microhardness and superficial morphology, and the recovery action of four remineralizing agents.

BACKGROUND: Dental bleaching is a common clinical practice. The aim of this study is to investigate the effect of 35% hydrogen peroxide (HP) bleaching gel on the morphology and microhardness of enamel, and to analyze the effect of four remineralizing agents. METHODS: One hundred blocks were prepared. The enamel surfaces were bleached with 35% HP in one session. The specimens were divided into four remineralization treatment groups (n = 25). G1: Tooth Mousse, G2: Remin-Pro, G3: Colgate Pro-Relif, G4: Mirafluor. The remineralizing protocol was applied 3 min per day for one week. Vickers microhardness (HV) measurements and SEM observations were performed at baseline, after bleaching, and after remineralizing treatment in all groups. Statistical analyses were performed using the paired t-test and ANOVA. RESULTS: After bleaching, SEM showed an increase of irregularities on the surface of the samples. Enamel microhardness decreased a mean of 47.7 HV, equivalent to a mean decrease of 18.3% (p < 0.05). After remineralization, the HV increased in all groups between 16 and 33% (p < 0.01), recovering the initial microhardness of enamel samples. SEM images revealed a higher quantity of superficial mineral deposits in groups 1 and 2 compared to the rest of the groups. CONCLUSIONS: The application of remineralizing products generates a significant increase in enamel microhardness. Tooth Mousse-treated samples showed a greater microhardness recovery, followed by Remin Pro. The superficial morphology of the samples reflects the results obtained in the HV tests.