Graupel Research Articles

Resveratrol-Loaded Dissolving Microneedles: Fabrication and in vitro Evaluation

AbstractResveratrol (Res), an active ingredient derived from a multitude of plants, exhibits multiple pharmacological activities. However, its poor water solubility and low bioavailability present significant challenges to its clinical application. Our study aimed to improve the transdermal absorption of Res using dissolving microneedle (MN) technology, which could effectively overcome the stratum corneum barrier. Res-loaded dissolving microneedles (Res-MNs) were fabricated using polyvinyl pyrrolidone K90 (PVP K90) as the matrix material, and a two-step casting procedure was employed. The process was optimized using the Box–Behnken experimental design approach. The characteristics of Res-MNs in vitro, including morphology, solubility, safety evaluation, and skin permeation, were studied. The results showed that the optimum preparation conditions of Res-MNs were a centrifugation time of 10 minutes, a solvent concentration of 25%, and a prescription ratio (Res: matrix) of 0.375. The skin permeability of the Res-MNs was enhanced compared with Res suspension and Res gel. The cumulative release of Res-MNs in vitro was 75%, which was approximately 5 and 3 times that of the Res suspension group and Res gel group. These results suggest that dissolving MNs may represent a potential approach for enhancing the transdermal delivery of poorly absorbed drugs such as Res.

Exosomes derived from Umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway.

Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Efficacy and Safety of a Fixed-Dose Combination Gel with Adapalene 0.1% and Clindamycin 1% for the Treatment of Acne Vulgaris (CACTUS): A Randomized, Controlled, Assessor-Blind, PhaseIII Clinical Trial.

Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. This was a randomized, controlled, assessor-blind, phaseIII study conducted in patients with moderate facial acne vulgaris. A total of 1617 patients were enrolled. At week12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95%CI - 19.95% to - 12.21%) and - 9.38% (95%CI - 13.25% to - 5.51%;), respectively. At week12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95%CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95%CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Adapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. ClinicalTrials.gov identifier NCT03615768.

Comprehensive Assessment of Intradermal Responses to Hyaluronic Acid-Based Skin Injection Fillers through Multi-Pathway Dynamic Synergies

Skin injection filling products must undergo a rigorous evaluation before entering the market, and intradermal reactions are crucial for biocompatibility. However, current evaluation methods for skin injection fillers often lack precision. This study aims to explore a comprehensive evaluation method by incorporating additional indicators: dermoscopy, transepidermal water loss, moisture content, ultrasound, and histological observation. Experimental findings show sodium hyaluronate gel groups exhibited no noticeable erythema or abnormalities, except for skin swelling. The dynamic and quantitative assessment of water content and transdermal water loss provided insights into the injection site skin's edema status. Ultrasound imaging observed subcutaneous material occupation and measured skin protrusion height. Histopathological observations revealed edema and inflammation in positive groups but no significant reactions in any gel samples. The comprehensive use of these methods confirms that the intradermal response of injection fillers in this study is within an acceptable range. However, if solely evaluated based on existing standards, it may exceed the qualified range. Consequently, the study suggests that for sodium hyaluronate gel, a macromolecular injection filler for long-term subcutaneous space occupancy, the traditional intradermal reaction scoring method may be inadequate. The proposed comprehensive evaluation scheme in this study is considered a more objective approach.

A comparative study of different soybean oil forms on the physicochemical properties of surimi myofibrillar protein gel: The role of soybean protein isolate and κ-carrageenan

Natural soybean oil, Pickering emulsion, high-internal-phase emulsion (HIPE), and emulsion gel were prepared to investigate their effects on the physicochemical properties of surimi myofibrillar protein gels. Their effects on gel strength ranked as: emulsion gel > Pickering emulsion > HIPE > soybean oil. At the same oil content, the emulsion gel exhibited higher G' than the other forms whereas natural oil exhibited the lowest G', and T22 was smaller in the emulsion gel group, indicating that the emulsion gel enhanced the interaction between water molecules and protein macromolecules. FT-IR testified that 9 % natural oil reduced the β-sheet content to 26.34 %, whereas Pickering emulsion, HIPE, and emulsion gel recovered the β-sheet content to 31.30 %, 36.17 %, and 32.69 %, respectively. Emulsion gel led to fewer voids, and the oil droplets in emulsion gel were more regularly spherical and homogeneously dispersed in the gel matrix, which might be attributed to the filling effects as well as “bridging action” of soybean protein isolate and κ-carrageenan within surimi proteins. In conclusion, we demonstrated emulsion gel as a good replacer to mitigate the negative effect of oil on the texture and structure of surimi gels, which would be a promising approach for oil supplementation in surimi production.

Comparative evaluation of hyaluronic acid-based dressing versus hydrocolloid dressing in rat dermal wound healing.

Wound healing is a complex process influenced by a variety of environmental factors. Dressing materials play a critical role in creating barriers against contaminants, maintaining optimal moisture levels, and absorbing wound exudate. Therefore, selecting materials tailored to wound characteristics is crucial for enhancing outcomes. Hyaluronic acid (HA) is a natural biocompatible polymer that supports healing by regulating inflammation and promoting tissue repair. This study compared HA- and hydrocolloid-based hydrogels in a rat model to optimize wound care strategies. Full-thickness dermal wounds (diameter, 8 mm) were created on the dorsal skin of 12 Sprague-Dawley rats under sevoflurane anesthesia. The wounds were treated with HA/silver sulfadiazine gel (group A), hydrocolloid gel (group B), or left untreated (control), all covered with a transparent dressing. Biopsy specimens on days 3, 7, and 21 were used to assess histological parameters: inflammatory cell infiltration, fibroblast infiltration, collagen deposition, neovascularization, and epithelial thickness, using a semi-quantitative scoring system. Histological analyses were conducted blindly, and statistical analyses were performed using the Kruskal-Wallis test (p< 0.05). On day 3, group A showed significantly higher inflammatory cell infiltration and collagen deposition than other groups, indicating extracellular matrix formation. By day 7, angiogenesis was highest in group A, followed by group B and controls. By day 21, all wounds had completely healed. Epithelial layer thickness, reflecting inflammation and fibroblast maturity, was significantly higher in group A. This study compared HA-based hydrogel and hydrocolloid-based dressings through histological analyses to elucidate wound healing mechanics. HA-based hydrogel dressings significantly enhanced wound recovery. However, generalizing these outcomes requires future studies to expand the range of effective wound treatment materials. These findings underscore the potential of HA-based dressings to enhance clinical outcomes in wound management, suggesting avenues for improving therapeutic strategies.

Intraovarian injection of 3D-MSC-EVs-ECM gel significantly improved rat ovarian function after chemotherapy

BackgroundRestoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement.MethodsHuman umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment.ResultsAfter culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel.ConclusionsOur study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure.

4DryField vs. hyalobarrier gel for preventing the recurrence of intrauterine adhesions – a pilot study

Introduction This was a single-center pilot study that sought to describe an innovative use of 4DryField® PH (premix) for preventing the recurrence of intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis in patients with Asherman’s syndrome (AS). Material and methods Twenty-three patients with AS were enrolled and 20 were randomized (1:1 ratio) to intrauterine application of 4DryField® PH (n = 10) or Hyalobarrier® gel (n = 10) in a single-blind manner. We evaluated IUAs (American Fertility Society [AFS] score) during initial hysteroscopy and second-look hysteroscopy one month later. Patients completed a follow-up symptoms questionnaire three and reproductive outcomes questionnaire six months later. Results The demographic and clinical characteristics, as well as severity of IUAs, were comparable in both groups. The mean initial AFS score was 9 and 8.5 in the 4DryField® PH and Hyalobarrier® gel groups, respectively (p = .476). There were no between-group differences in AFS progress (5.9 vs. 5.6, p = .675), need for secondary adhesiolysis (7 vs. 7 patients, p = 1), and the follow-up outcomes. Conclusion 4DryField® PH could be a promising antiadhesive agent for preventing the recurrence of IUAs, showing similar effectiveness and safety to Hyalobarrier® gel. Our findings warrant prospective validation in a larger clinical trial. Clinical trial registry number ISRCTN15630617

Effectiveness of 0.2% Hyaluronic Acid on Clinical, Biomolecular and Microbiological Parameters in Type 2 Diabetes Mellitus Patients with Periodontitis.

This double-blind randomized clinical trial assessed the effectiveness of 0.2% hyaluronic acid (HA) gel as an adjunct to scaling and root planning (SRP) in patients with periodontitis and type 2 diabetes mellitus (DM), focusing on changes in clinical periodontal parameters, the expression of inflammatory mediators, and oral pathogens. The randomized clinical trial involved 36 participants, 18 DM patients, and 18 healthy patients. The participants in each group were randomly assigned to receive placebo or HA gel after SRP. Gingival crevicular fluid and subgingival plaque samples were taken before treatment and at 4-week follow-up. Clinical parameters, interleukin-1β (IL-1β) and IL-10 levels, and proportions of Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) were evaluated at baseline and follow-up. Paired t-test (parametric data) or Wilcoxon signed-rank test (nonparametric data) was used for intragroup comparison between baseline and follow-up, and comparisons between groups one-way analysis of variance test (parametric data) or Kruskal-Wallis test (nonparametric data). At 4 weeks, most of the groups showed statistically significant decreases (p ≤ 0.05) in various clinical and biomolecular parameters. However, there were exceptions: the pocket probing depth (PPD) and clinical attachment loss (CAL) parameter did not significantly decrease for the placebo (p > 0.05) non-DM group, and the IL-10 parameter in the DM HA gel group (p = 0.108). Regarding bacterial proportions, the non-DM and DM placebo group exhibited significant test results for Pg after 4 weeks (p ≤ 0.05). In the case of Fn bacteria proportions, they decreased in all groups, but these results were not statistically significant (p ≥ 0.05). An intergroup analysis revealed no significant differences (p ≤ 0.05) for bleeding on probing (BOP), PPD, and both proinflammatory and anti-inflammatory cytokines. Only clinical attachment loss (CAL) exhibited a statistically significant intergroup difference 0.042. The use of 0.2% HA gel into periodontal pockets alongside SRP, for both diabetic and healthy individuals, showed no statistically significant variances in clinical, biomolecular, and microbiological measures.

Radar-Derived Convective Features and Atmospheric Environments of Hail-Producing Storms over the Contiguous United States

Abstract Hail smaller than 0.75 in. is known to cause economic impacts yet remains understudied due to report biases towards recording larger hail sizes (≤1 in.). In this study, we assembled ground hail reports during 2017–22 from the National Centers for Environmental Information (NCEI) Storm Data, Community Collaborative Rain, Hail and Snow Network (CoCoRaHS), and Meteorological Phenomena Identification Near the Ground (mPING) databases. Then, these reports are collocated with the attributes of radar-derived convective features from the Multi-Radar Multi-Sensor (MRMS) system and fifth major global reanalysis produced by European Centre for Medium-Range Weather Forecasts (ERA5) atmospheric vertical profiles to construct a dataset describing properties of a full spectrum of hailstorms. The characteristics of radar reflectivity and atmospheric profiles are examined for hail of different sizes reported within selected regions over the contiguous United States (CONUS). In addition to the seasonal and diurnal variations, the morphology of convective features shows apparent regional differences from west to east in CONUS. The maximum expected size of hail (MESH) performance against reported hail sizes shows underestimation of hail with significant sizes and overestimation of small hail sizes. ERA5 vertical atmospheric profiles are explored to form relationships between storm environment and hail sizes. In addition to the relationships between wind shear and hail sizes, the roles of low-level relative humidity and freezing level height in regard to hail melting are discussed.

Synthesis and evaluation of transdermal rosuvastatin-loaded ultradeformable vesicles: Restoring the serum lipid profile in poloxamer 407-caused hyperlipidemia

The present study aimed to design, optimize and characterize rosuvastatin calcium-loaded transfersomes (ROS-TFs) for potential transdermal application and improved the antihyperlipidemic effect of ROS. ROS-TFs were prepared by the lipid thin film hydration method using soy phosphatidylcholine (SPC) to form lipid bilayers and tween 80 (T80) or sodium cholate (SC) as an edge activator (EA). The ROS-TFs were optimized for several parameters, including the proportions of SPC and EA, the particle size (PS) and the entrapment efficiency (EE%). The optimized formulation showed a PS of 169 ± 0.7 nm, zeta potential (ZP) of −19.05 ± 0.4 mV, polydispersity index (PDI) of 0.19 ± 0.02 and EE% of 72.71 ± 1.77. The optimized formulation was further incorporated into a Carbopol 940 gel to obtain a rosuvastatin calcium-loaded transfersomal gel (ROS-TFG) to prolong its residence time on skin. The resulting ROS-TFs exhibited sustained drug release followed by ROS-TFG after 2 h at a pH of 7.4. Skin permeation studies showed enhanced skin permeation of ROS-TFs compared to that of the plain drug gel at a pH of 7.4. In vivo antihyperlipidemic results demonstrated a significant improvement in the lipid profile of the ROS-TFG group in contrast to that of the plain drug gel group. Taken together, these findings indicate that ROS-TFs could be promising nanocarriers for transdermal drug delivery with enhanced antihyperlipidemic effects in the treatment of hyperlipidemia.

Antibacterial Efficacy of Benzalkonium Chloride Gel with Tongue Brush on S. Mutans and L. Acidophilus and Tongue Coating – A Randomized Controlled Trial

Introduction: The tongue microbiota, like other parts of the oral cavity, plays a significant role in the development of dental caries. S. mutans and L. acidophilus species, are associated with the initiation and progression of dental caries.  Aim: To assess the efficacy of benzalkonium Chloride gel along with tongue cleaning aids in the reduction of tongue coating and bacterial count on dorsal surface of the tongue.  Materials and Methods: A double blinded randomized control trial was conducted among 17-25 years old college students. A total of 60 participants were randomly divided into 4 groups according to their use of tongue cleaning aids as follows: Group A, Tongue Brush Alone; Group B, Tongue Brush with Chlorhexidine Mouthwash (Clohex ADS); Group C, Tongue Brush with Chlorhexidine Gel (Hexigel); and Group D, Tongue Brush with Benzalkonium Chloride Gel. The Winkel tongue coating index (WTCI) was used to measure the tongue coating at baseline and at 14th day and the participant’s tongue coatings on dorsal surface were sampled using swab method, and the number of S. mutans and L. acidophilus colonies were counted before and after intervention.  Results: Both the Hexigel group and Benzalkonium chloride gel group reduced both the bacterial load and tongue coating at 14th Day compared to the baseline data.  Conclusion: This study suggests that usage of Tongue brush along with Benzalkonium Chloride gel decreased the tongue coating and the number of bacteria on the dorsal tongue surface.

The chromatograph evaluation of white spot lesion treated with magnesium gel and diode laser: an in vitro study

Objective. White spot lesions are one of the most common concerns of orthodontic therapy. The present study was accomplished to evaluate the ability of Magnesium gel at different concentration and diode laser in combination compared with commercially available 1.23% APF in color restoring of WSL on permanent teeth. Methods. 42 extracted sound upper premolar teeth were recruited for this study. WSL was artificially induced, until it appears in wet and dry condition on buccal surface of each tooth. Different approaches have been utilized for treatment WSL. 6 experimental groups were involved: Group A: Control, Group B: 0.5%MgCl2 gel, Group C: 1%MgCl2 gel, Group D: 0.5%MgCl2 gel and Diode laser, Group E: 1%MgCl2 gel and Diode laser and Group F: 1.23%APF. The difference between the displayed color and the original color standard (ΔE) was assessed by colorimeter. The surface topography of teeth samples from each tested group was examined by a SEM. Collected data were investigated using one-way ANOVA followed by Duncan post hoc test at p ≤0.05. Result. A significant difference in (ΔE) was noticed among groups (p = 0.006). Group (B) showed the lowest ΔE value (9.4 ± 1.6), followed by group (D) (10.2 ± 1.1), group (F) (10.4±2.6), group (A) (11.6 ± 1.3), group (C) (12.9 ± 2.3) and group (E) (13.2 ± 1.3). Conclusion. In present study, topical application of 0.5% MgCl2 gel ensure color reinstating compared to other groups.

Influence of metal-phenolic networks on the properties of soy protein isolates gels

In this study, epigallocatechin-3-gallate (EGCG) was preliminarily coordinated with three types of metal ions to form metal-phenolic networks (MPNs) solutions, which were introduced into soy protein isolate (SPI) solutions to prepare SPI-MPNs composite hydrogels. This study aims to compare the effects of different types and varying addition levels of MPNs on the structure and mechanical properties of SPI gels. Dynamic light scattering and XPS results show that MPNs increase particle sizes in the composite system, and hydrogen bonding between MPNs and SPI causes smaller SPI molecules to aggregate into larger protein clusters. Low-field nuclear magnetic resonance analysis indicates that SPI-MPNs composite gels retain more water, with the majority of the water being successfully immobilized within the gel network. Rheological and textural analysis results indicate that the presence of MPNs can form a more rigid structure, significantly enhancing the mechanical properties of the composite gels. The group of gels with the highest strength exhibited a G’ value that was 2.1 times higher than that of the SPI gels, indicating the formation of a more stable three-dimensional network structure. These findings have significant potential implications for the application of SPI-MPNs composite gels in the food industry.

Preparation of photo-crosslinked microalgae-carboxymethyl chitosan composite hydrogels for enhanced wound healing

Integrating microalgae into wound dressings has proven effective in promoting chronic wound healing through photosynthesis-induced oxygen release. However, challenges such as high crosslinking temperatures and prolonged gel molding processes limit microalgae growth and reduce the overall therapeutic impact. In this work, inspired by cell-symbiotic photo-crosslinked hydrogels, we present a novel photo-crosslinked microalgae carboxymethyl chitosan composite hydrogel. This hydrogel completes crosslinking at room temperature within 30 s, enhancing chronic wound healing. The composite gel incorporates photosynthesizing unicellular microalgae (Chlamydomonas reinhardtii) and the antimicrobial agent ciprofloxacin during preparation. In light, the gel continues to photosynthesize, releasing oxygen while simultaneously acting as an antibacterial agent. This dual action results in the upregulation of CD31 and VEGFA levels and the downregulation of HIF-1α levels in diabetic wounds. The wound closure rate reached approximately 96.70 % on day 12 in the composite gel group, compared to only 78.98 % in the control group. Therefore, the composite gel promotes healing by reducing local hypoxia, encouraging angiogenesis, and lowering infection risk. These results suggest that photo-crosslinked microalgae composite gels provide an effective strategy for localized oxygen delivery to promote wound healing and offer a viable method for rapidly preparing living biomaterials under suitable conditions.

Mechanical force promotes tissue and molecular changes in adipose tissue regeneration post-transplantation.

Fat grafting often yields inconsistent and suboptimal results, necessitating improved fat processing techniques. A stromal vascular fraction (SVF) gel created using mechanical emulsification demonstrates superior retention rates to conventional Coleman fat grafts. This study investigated the mechanisms at play by transplanting fat aspirates from liposuction patients-either processed as Coleman fat grafts or further refined into an SVF gel via mechanical shear force-onto the backs of nude mice. The retention rate of the SVF gel after transplantation surpassed that observed for Coleman fat. Hematoxylin and eosin (HE) staining and immunofluorescence results demonstrated that the SVF gel group could form new adipose tissue characterized by well-organized mature fat structures. Mechanical shear force application induced increased mesenchymal stem cell abundance. Rather than merely surviving regeneration, fat was regenerated after transplantation, and the regenerated cells were mainly from mice, which was supported by microarray analysis. RNA-seq highlighted 601 genes expressed between SVF gel and Coleman fat groups, with 164 genes upregulated (cell cycle processes), and 437 genes downregulated (lipid metabolism). The application of mechanical shear force reduces the risk of complications and fosters cell proliferation and division, thereby enhancing the retention and regeneration of transplanted fat.

Evaluation of the Effectiveness of Obstetric Lubricant Gel in Labor in Nulliparous and Primiparous Women: A Randomized Controlled Study

Aim: Our hypothesis was that lubricating gels used at the beginning of the active phase of labor could reduce the incidence of episiotomies and shorten the duration of labor. This study aims to investigate and confirm this theory with a randomized controlled trial. Material and Methods: A prospective randomized controlled trial was conducted at obstetrics and gynecology department of a university hospital between January 2017 and April 2017. The study included 102 nulliparous and 93 primiparous singleton pregnancies. 50 primiparous women and 47 nulliparous patients were randomly assigned to the obstetric gel group. Obstetric gel was applied to participants in the study groups at the beginning of the active phase of labor. Outcomes were episiotomy rates and duration of labor. Results: Episiotomy rates were significantly lower in nulliparous obstetric gel group (36.1% and 63.6%, p=0.005). The duration of the active phase of the first and second stage of labor was significantly lower in the obstetrical gel groups compared to the control groups in both parities (150 ± 86 and 203. 5 ± 134, p=0.021, 28.8 ± 18.2 and 62.6 ± 53.8, p

Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model.

Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massive rotator cuff defects includes complete or partial repair and patch augmentation. However, because of the tendon's limited regenerative ability, the tendon retear risk after rotator cuff defect repair is still high. Thus, a new therapy is needed to promote tendon regeneration for repair of massive rotator cuff defects. Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipital tendon patches, which is comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What is the potential of the tissue-engineered bicipital autologous tendon patch to promote tendon regeneration? In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an assay of live/dead cell viability, cell counting kit-8 (CCK-8) assay, and Sirius red staining, respectively. The in vivo animal study was conducted using 8- to 12-week-old New Zealand White rabbits. The left shoulder of each animal was operated on, with equal numbers of males and females. There were 12 rabbits in the control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch groups at 2-month time point. Through an infraspinatus tendon defect model, the effectiveness of tissue-engineered bicipital autologous tendon patches (patch group) in tendon repair was assessed compared with untreated (control group) and fibrin glue (gel group) treatments in vivo. This assessment included histological evaluation of repaired tissue morphology, transmission electron microscopy (TEM) evaluation of regenerated collagen fibrils, and RNA sequencing to explore the potential mechanisms of tissue-engineered bicipital autologous tendon patches in tendon regeneration. In vitro experiments demonstrated that fibrin glue enhanced the collagen synthesis ability of tendon stem/progenitor cells (0.38 ± 0.02) compared with standard cell culture alone (0.27 ± 0.02, mean difference 0.11 [95% CI 0.07 to 0.14]; p < 0.001). With prolonged cultivation, the cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% ± 3.68%) compared with 11 days (13.05% ± 8.78%, mean difference -65.08% [95% CI -77.99% to -52.15%]; p＜0.001), 7 days (2.67% ± 2.62%, mean difference -75.46% [95% CI -88.37% to -62.53%]; p＜0.001), and 1 day (0.33% ± 0.30%, mean difference -77.80% [95% CI -90.71% to -64.87%]; p＜0.001). At 3 months after transplantation, in vivo experiments revealed that compared with the control and gel groups, the patch group displayed improved repair outcomes. This was evidenced by better histological scores in the patch group (3.83 ± 2.01) compared with the gel group (10.67 ± 0.58, mean difference 6.84 [95% CI 3.67 to 10.00]; p = 0.001) and control group (10.75 ± 0.66, mean difference 6.92 [95% CI 3.75 to 10.08]; p = 0.001), and by regular alignment and larger diameters of newly formed collagen fibrils in the patch group (77.52 ± 44.41 nm) compared with the control group (53.34 ± 6.64 nm, mean difference 24.18 [95% CI 22.24 to 26.11]; p < 0.001). RNA sequencing analysis revealed that a tissue-engineered bicipital autologous tendon patch facilitated tendon regeneration by modulating the immune response, promoting collagen fibril organization, and alleviating vasoconstriction. This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promotion of tendon regeneration. The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects during clinical rotator cuff surgery. Subsequent research could focus on large animal experiments using a tissue-engineered bicipital autologous tendon patch to explore their feasibility for clinical translation.

Comparison of liposomal gel with and without chamomile to prevent radiation dermatitis in breast cancer patients: arandomized controlled trial.

To compare aliposomal gel with and without chamomile extract for the prevention of radiation dermatitis in breast cancer patients undergoing radiotherapy. This study was adouble-blind randomized clinical trial. Atotal of 100 participants undergoing radiotherapy for breast cancer were recruited. The primary outcome was the occurrence of dry desquamation. Cumulative dose of ionizing radiation at the first occurrence of dry desquamation, occurrence of erythema, moist desquamation, global radiation dermatitis, and any signs and symptoms self-reported by participants were secondary outcomes. Dry desquamation occurred in 6.0% of the participants using chamomile liposomal gel and 12.2% of those using liposomal gel (p = 0.32). The mean cumulative dose of ionizing radiation for the first occurrence of dry desquamation was 45.1 Gy in the chamomile liposomal gel group and 43.7 Gy in the liposomal gel group. There were no differences between the two gels in the occurrence of erythema, dry desquamation, moist desquamation, and radiation dermatitis compared to liposomal gel. There was alower proportion of reported symptoms in the chamomile liposomal gel group compared to liposomal gel group in the first 3weeks of radiation, especially for itching (p = 0.05). No statistically significant differences between the two gels were found in radiation dermatitis occurrence and dose at first occurrence. Comparing to the literature, it seems that both interventions may be effective, which might explain the lack of statistical difference between the groups.

Effects of HyaRegen gel on tumour proliferation of colorectal peritoneal metastases.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a valuable therapeutic alternative for patients with peritoneal metastases. PIPAC uses a hyaluronic acid-based gel to reduce surgically induced adhesions. The aim of this study was to evaluate the effects of the hyaluronic acid-based gel on tumor dissemination. First, we explored whether the survival of CT26 luciferase-expressing murine colonic tumor cells was correlated with the dose of HyaRegen® Gel, and we determined the half-maximal inhibitory concentration (the IC50) of the gel. Next, we performed an in vitro study of cell survival rates after gel application on day 0 (D0) and day 1 (D1). Finally, we intraperitoneally administered the gel to mice with immunocompetent BALB/c colonic peritoneal metastases (on D0, D5, D10, D14, and D18). Tumor growth was regularly monitored using a bioluminescence assay (on D11, D17, and D21). After all mice had been sacrificed on D21, the body weights and the volumes of intraperitoneal ascites were measured; the Peritoneal Carcinosis Index (PCI) and Ki-antigen 67 scores were calculated. The IC50 value was 70 μL of gel in a total volume of 100 μL. The cell survival rates on D4 were identical in the control group and the two groups that had been treated with gel on D0 and D1. The bioluminescence levels over time were similar in the gel and control groups. The PCI scores were 35.5 ± 2.89 for the control group and 36 ± 2.45 for the gel group (p = 0.8005). The mean Ki-67 index percentages were 37.28 ±1 1.75 for the control group and 34.03 ± 8.62 for the gel group (p = 0.1971). This in vitro and in vivo study using a mouse model of immunocompetent metastatic peritoneal cancer did not reveal any pro- or anti-tumoral effect of HyaRegen® Gel. These findings indicate that the gel can be used to treat PIPACs with minimal apprehension.