Search Results (51)

Objectives: Burn being a major traumatic issue worldwide impacts millions of lives annually. Herein, a novel xanthan dialdehyde/sodium alginate/copper-doped mesoporous bioactive glass nanoparticle (XDA/Na-ALG/Cu-MBGN) hydrogel is presented in this study. Methods: The hydrogel was fabricated by a casting method, followed by its characterization in terms of its morphology, surface topography, and in vitro biochemical and physical interactions. Results: Scanning electron microscopy images revealed the rough surface of the hydrogel, ideal for cell attachment and proliferation. The nanoporous structure revealed by BET enabled it to hold moisture for an extended span. The nanopores were developed because of the ether linkage developed between XDA and Na-ALG, as evident from Fourier Transform Infrared Spectroscopy. The loading of Cu-MBGNs was also confirmed by FTIR. The release of copper ions was sustained throughout the 7 days, and it is accounting for about 22 µg/mL in 330 h, which follows the degradation kinetics of XDA/Na-ALG/Cu-MBGN hydrogels. The released copper ions promoted angiogenesis, as confirmed by the enhanced release of vascular endothelial growth factor (VEGF) for the XDA/Na-ALG/Cu-MBGN hydrogel (275 ng/mL) in comparison to 200 ng/mL of the bare TCP. The hydrogel, despite being bactericidal against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) did not show toxicity towards human dermal fibroblasts confirmed via a Water-Soluble Tetrazolium 8 assay. Conclusions: Hence, the developed XDA/Na-ALG/Cu-MBGN hydrogel possesses potential to be investigated further in terms of in vivo interactions. Full article

This study presents a novel hydrogel formulation combining mupirocin, a broad-spectrum antibiotic, with keratinocyte growth factor (KGF) to enhance wound healing through antibacterial action and tissue regeneration. Mupirocin was encapsulated in hydroxypropyl β-cyclodextrin (HP-β-CD) and stabilized with poly(amidoamine) dendrimers (PAMAM). Molecular docking studies assessed mupirocin’s binding to PAMAM and its interaction with isoleucyl-tRNA synthetase. Physicochemical properties—including zeta potential, particle size, and surface tension—were characterized, and drug release kinetics were evaluated using Franz diffusion cells. In vitro assays on human dermal fibroblasts (HS27) included proliferation, scratch wound healing, and flow cytometry to assess cellular behavior. Antibacterial efficacy was determined via the Kirby–Bauer disk diffusion method. Results showed strong binding of mupirocin to its target enzyme, enhanced by KGF. The hydrogel exhibited favorable properties: surface tension of 24.7 dyne/cm, zeta potential of −24.79 mV, and particle size of ~119 nm, indicating high stability. Franz diffusion revealed sustained drug release compared to commercial mupirocin. Cellular assays demonstrated significant fibroblast migration and proliferation, with flow cytometry confirming increased wound healing markers. The formulation showed potent antimicrobial activity, including against Methicillin-resistant Staphylococcus aureus (MRSA), highlighting its promise for infected wound treatment and advanced clinical wound care. Full article

Background/Objectives: Ultradeformable liposomes represent an established platform for topical delivery of antioxidant compounds, thanks to their structural flexibility and ability to enhance skin permeation, but standardized manufacturing protocols are still lacking. This study presents a microfluidic-based strategy for the scalable production of ultradeformable liposomes encapsulating Stellaria media extract, a polyphenol-rich phytocomplex with strong antioxidant activity. Methods: Liposomes were produced with a GMP-like microfluidic platform enabling fine control of formulation parameters and high reproducibility under conditions directly transferable to continuous manufacturing. Process optimization tested different total flow rates. Characterization included particle size and distribution, encapsulation efficiency, colloidal stability and kinetics of release. Permeation was assessed with Franz diffusion cells using human stratum corneum and epidermidis membranes. Results: Optimal conditions were a flow rate ratio of 3:1 and a total flow rate of 7 mL/min, yielding ultradeformable liposomes with a mean size of 89 ± 1 nm, a polydispersity index < 0.25, and high encapsulation efficiency (72%). The resulting formulation showed long-term colloidal stability and controlled release. Diffusion studies demonstrated a 2-fold increase in permeation rate compared to the free extract. Conclusions: These findings highlight the potential of microfluidics as a robust and scalable technology for the industrial production of ultradeformable liposomes designed to enhance the dermal delivery of bioactive phytocomplex for both pharmaceutical and cosmeceutical applications. Full article

Background/Objectives: Physiologically based kinetics (PBK) modelling provides (internal) exposure concentrations. We used a PBK model parameterized exclusively with in silico and in vitro data in a bottom-up approach to predict the pharmacokinetics of oxybenzone, a UV filter, present in two formulations (for which dose-normalized C_max and AUC from clinical studies were different). Methods: Skin absorption data were used to refine chemical-specific dermal absorption parameters for oxybenzone in a lotion and spray. The Transdermal Compartmental Absorption and Transit (TCAT) model in GastroPlus^® 9.9 was used to estimate vehicle and skin layer diffusion and partitioning and then used to simulate systemic exposure. The model was validated according to the OECD 331 guideline. Results: PK profiles simulated for both formulations after single and repeated applications correlated with clinical data profiles (used only to validate our approach), with a deviation from the C_max and AUC of <2-fold. Sensitivity and uncertainty analyses indicated that most input parameters had a medium to high reliability, whereas only a few parameters related to dermal delivery had a low reliability: the partition coefficient between vehicle and water for spray and the diffusion coefficient in stratum corneum for lotion. In vitro skin absorption results suggested that absorption kinetics were not statistically different between the formulations; however, parameters such as vehicle evaporation time were different. The fine-tuned TCAT model containing the absorption data suggested that the variability in clinical data might be due to other factors, e.g., the small number of subjects. Conclusions: These results demonstrate how formulation-dependent absorption kinetics improve confidence in estimated exposure, thanks to the PBK model with its bottom-up approach for nonanimal-based safety assessments. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

This study characterized collagen remodeling in an electron-beam-sterilized porcine acellular dermal matrix (E-PADM) by evaluating host response kinetics during wound healing. E-PADM (n = 6 lots/time point) was implanted in an abdominal wall bridging defect in nonhuman primates (N = 24). Histological, immunohistochemical, and biochemical assessments were conducted. Pro-inflammatory tissue cytokines peaked 1 month post-implantation and subsided to baseline by 6 months. E-PADM-specific serum immunoglobulin G antibodies increased by 213-fold from baseline at 1 month, then decreased to <10-fold by 6–9 months. The mean percentage tissue area staining positively for matrix metalloproteinase-1 plateaued at 3 months (40.3 ± 16.9%), then subsided by 6 months (16.3 ± 11.1%); tissue inhibitor matrix metalloproteinase-1 content plateaued at 1 month (39.0 ± 14.3%), then subsided by 9 months (13.0 ± 8.8%). Mean E-PADM thickness (1.7 ± 0.2 mm pre-implant) increased at 3 months (2.9 ± 1.5 mm), then decreased by 9 months (1.9 ± 1.1; equivalent to pre-implant). Histology demonstrated mild inflammation between 1–3 months, then a peak in host tissue deposition, with ≈75%–100% E-PADM collagen turnover, and fibroblast infiltration and neovascularization between 3–6 months. Picrosirius red staining revealed that mature E-PADM collagen was replaced by host-associated neo-collagen by 6 months. E-PADM implantation induced wound healing, which drove dermal E-PADM collagen remodeling to native, functional fascia-like tissue at the implant site. Full article

Pesticide residues pose risks to the environment and human health. Little is known about how tillage and straw management affect herbicide behavior in soil. This study investigated the effects of different tillage practices under varying straw incorporation scenarios on the degradation of five commonly used herbicides in a long-term experimental field located in the maize belt of Siping, Jilin Province. Post-harvest soil samples were analyzed for residual herbicide concentrations and basic soil physicochemical properties. A human health risk assessment was conducted, and a controlled incubation experiment was carried out to evaluate herbicide degradation dynamics under three management systems: straw incorporation with traditional rotary tillage (ST), straw incorporation with strip tillage (SS), and no-till without straw (CK). Residual concentrations of atrazine ranged from not detected (ND) to 21.10 μg/kg (mean: 5.28 μg/kg), while acetochlor showed the highest variability (2.29–120.61 μg/kg, mean: 25.26 μg/kg). Alachlor levels were much lower (ND–5.71 μg/kg, mean: 0.34 μg/kg), and neither nicosulfuron nor mesotrione was detected. Soil organic matter (17.6–20.89 g/kg) positively correlated with available potassium and acetochlor residues. Health risk assessments indicated negligible non-cancer risks for both adults and children via ingestion, dermal contact, and inhalation. The results demonstrate that tillage methods significantly influence herbicide degradation kinetics, thereby affecting environmental persistence and ecological risks. Integrating straw with ST or SS enhanced the dissipation of atrazine and mesotrione, suggesting their potential as effective residue mitigation strategies. This study highlights the importance of tailoring tillage and straw management practices to pesticide type for optimizing herbicide fate and promoting sustainable agroecosystem management. Full article

Occupational exposure to commercial formic and acetic acids through dermal contact and inhalation during rubber sheet processing poses significant health risks to workers. Additionally, the use of these acids contributes to environmental pollution by contaminating water sources and soil. This study investigates the potential of three types of wood vinegar—derived from para-rubber wood, bamboo, and eucalyptus—obtained through biomass pyrolysis under anaerobic conditions, as sustainable alternatives to formic and acetic acids in the production of ribbed smoked sheets (RSSs). The organic constituents of each wood vinegar were characterized using gas chromatography and subsequently mixed with fresh natural latex to produce coagulated rubber sheets. The physical and chemical properties, equilibrium moisture content, and drying kinetics of the resulting sheets were then evaluated. The results indicated that wood vinegar derived from para-rubber wood contained a higher concentration of acetic acid compared to that obtained from bamboo and eucalyptus. As a result, rubber sheets coagulated with para-rubber wood and bamboo vinegars exhibited moisture sorption isotherms comparable to those of sheets coagulated with acetic acid, best described by the modified Henderson model. In contrast, sheets coagulated with eucalyptus-derived vinegar and formic acid followed the Oswin model. In terms of physical and chemical properties, extended drying times led to improved tensile strength in all samples. No statistically significant differences in tensile strength were observed between the experimental and reference samples. The concentration of acid was found to influence Mooney viscosity, the plasticity retention index (PRI), the thermogravimetric curve, and the overall coagulation process more significantly than the acid type. The drying kinetics of all five rubber sheet samples displayed similar trends, with the drying time decreasing in response to increases in drying temperature and airflow velocity. Full article

This study presents novel skin-compatible biomaterials based on guar gum and dextran sulfate matrices, incorporating softwood lignin, lignin esterified with aspartic acid, and Rosa canina extract. The materials were prepared via casting and evaluated for physicochemical, mechanical, and biological properties. Spectroscopic analyses confirmed successful lignin esterification, with new carbonyl and amide peaks and a nitrogen signal (3.83%) detected. Rosa canina extract enhanced the Young’s modulus from 1.42 MPa to 3.18 MPa and reduced elongation at break from 34.88 mm to 25.19 mm. The combination of esterified lignin and Rosa canina showed the greatest mechanical reinforcement (3.74 MPa modulus, 23.78 mm elongation). Swelling capacity decreased from 0.40 to 0.23 g water/g material and followed pseudo-second-order kinetics (R² = 0.991–0.998). The release of Rosa canina bioactives followed the Makoid–Banakar model, indicating a transition from rapid to sustained release. All formulations exhibited anti-inflammatory activity with over 45% protein denaturation inhibition, peaking at 61.58% for the Rosa canina-only sample. In vitro biocompatibility assays demonstrated over 80% cell viability, confirming the potential of these biomaterials for dermal applications. Full article

Facial aging is a multifactorial and stratified biological process characterized by progressive morphological and biochemical alterations affecting both cutaneous (Layer I) and subcutaneous (Layer II) tissues. These age-related changes manifest clinically as volume depletion, tissue ptosis, and a decline in overall skin quality. In response to these phenomena, thread lifting techniques have evolved significantly—from simple mechanical suspension methods to sophisticated bioactive platforms. Contemporary threads now incorporate biocompatible polymers and hyaluronic acid (HA), aiming not only to reposition soft tissues but also to promote dermal regeneration. This review provides a comprehensive classification and critical assessment of thread lifting materials, focusing on their chemical composition, mechanical performance, degradation kinetics, and biostimulatory potential. Particular emphasis has been given to the surface integration of HA into monofilament threads, especially with the emergence of advanced delivery systems such as NAMICA, which facilitate sustained HA release. Advanced thread materials, especially those fabricated from poly(L-lactide-co-ε-caprolactone) [P(LA/CL)], demonstrate both tensile support and regenerative efficacy. Emerging HA-covered threads exhibit synergistic bioactivity, stimulating skin remodeling. NAMICA technology represents an advancement in the field, in which HA is encapsulated within biodegradable polymer fibers to enable gradual release and enhanced dermal integration. Nonetheless, well-designed human studies are still needed to substantiate its therapeutic efficacy. Consequently, the paradigm of thread lifting is shifting from purely mechanical interventions toward biologically active systems that promote comprehensive ECM regeneration. The integration of HA into resorbable threads, especially when combined with sustained-release technologies, represents a meaningful innovation in aesthetic dermatology, meriting further preclinical and clinical evaluation. Full article

Background/Objectives: Microneedles represent an innovative transdermal drug delivery approach, especially for protein antigens. This study aimed to develop a dual-functional, dissolvable microneedle system loaded with β-glucan and fucoidan in a hyaluronic acid matrix to achieve transdermal immunomodulation and reactive oxygen species (ROS) regulation, exploring its potential in inflammatory disease management and antigen delivery. Methods: The microneedles were fabricated using a two-step casting method. Their morphology, mechanical strength, and dissolution kinetics were characterized. In vitro experiments evaluated the ROS-modulating effects on human dermal fibroblasts, while in vivo studies on C57 mice investigated immune activation and lymph node accumulation of ovalbumin antigen. Results: The microneedles exhibited a mechanical strength exceeding 7.45 N/needle and dissolved within 50 s. β-glucan transiently reduced ROS levels at 6 h followed by a rebound, whereas fucoidan sustained ROS suppression after 12 h. In mice, β-glucan-loaded microneedles triggered local immune activation, and fucoidan-incorporated microneedles enhanced ovalbumin accumulation in lymph nodes by 2.1-fold compared to controls. Conclusions: Integrating β-glucan’s immunostimulatory and fucoidan’s ROS-scavenging/lymphatic-targeting properties within a single microneedle platform offers a promising multifunctional strategy for treating inflammatory diseases and delivering protein antigens. Full article

Background/Objectives: Dermal interstitial fluid (dISF) is probably the most interesting biofluid for biomarker analysis as an alternative to blood, enabling higher patient comfort and closer or even continuous biomarker monitoring. The prerequisite for dISF-based analysis tools is having convenient access to dISF, as well as a better knowledge of the presence, concentration, and dynamics of biomarkers in dISF. Hollow microneedles represent one of the most promising platforms for access to pure dISF, enabling the mining of biomarker information. Methods and Results: Here, a microneedle-based method for dISF sampling is presented, where a combination of hollow microneedles and sub-pressure is used to optimize both penetration depth in skin and dermal interstitial fluid sampling volumes, and the design of an open, prospective, exploratory, and interventional study to examine the detectability of inflammatory and cardiocirculatory biomarkers in the dISF of heart failure patients, the relationship between dISF-derived and blood-derived biomarker levels, and their kinetics during a cardiopulmonary exercise test (CPET) is introduced. Conclusions: The dISF sampling method and study presented here will foster research on biomarkers in dISF in general and in heart failure patients in particular. The study is part of the European project DIGIPREDICT—Digital Edge AI-deployed DIGItal Twins for PREDICTing disease progression and the need for early intervention in infectious and cardiovascular diseases beyond COVID-19. Full article

The genitourinary syndrome of menopause (GSM) is a prevalent condition impacting a substantial number of women globally. Presently, the management of GSM typically entails the administration of estrogen via oral, dermal, or vaginal routes for a prolonged period of time. This study involves the development of a polymer-based hollow cylindrical delivery system loaded with estradiol hemihydrate (E2) for prolonged delivery to the uterine cavity (EPHCD) combined with a norethindrone acetate (NETA)-loaded polymeric matrix (NLPM), with both units placed onto an intra-uterine device to form a multi-component drug delivery system for the management of GSM (MCDDS). In developing EPHCD, a central composite design (CCD) was employed to evaluate and optimize the impact of formulation factors on EPHCD release and unit weight loss. The optimized EPHCD was further assessed for its chemical integrity, surface morphology, hydration characteristics, release behavior, ex vivo permeation and cytocompatibility. The optimized EPHCD, which featured a high drug load (10%) and low ethyl cellulose-to-polycaprolactone ratio (EC-to-PCL, 10%), demonstrated favorable attributes with a cumulative drug release and weight loss of 23.78 ± 0.84% and 2.09 ± 0.21%, respectively, over a 4-week testing period. The release kinetics were further noted to obey the Peppas–Sahlin model. Evaluation of MCDDS revealed an in vitro drug release comparable to the individual units, with permeation studies displaying an initial increase in the rate of flux for both drugs during the first 2 h, followed by a subsequent decrease. Moreover, the MCDDS components showed good cytocompatibility against NIH/3T3 cells, with cell viability of more than 70%. Upon evaluation of the MCDDS system, the results of this study highlight its potential as a viable sustained-release intrauterine platform for the treatment of GSM. Full article

To improve wound healing, advanced biofabrication techniques are proposed here to develop customized wound patches to release bioactive agents targeting cell function in a controlled manner. Three-dimensional (3D) bioprinted “smart” patches, based on methacrylated gellan gum (GGMA), loaded with tannic acid (TA) or L-ascorbic acid (AA) have been manufactured. To improve stability and degradation time, gellan gum (GG) was chemically modified by grafting methacrylic moieties on the polysaccharide backbone. GGMA patches were characterized through physicochemical, morphological and mechanical evaluation. Kinetics release and antioxidant potential of TA and AA as well as antimicrobial activity against common pathogens Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli in accordance with ISO 22196:2011 are reported. The cytocompatibility of the patches was demonstrated by direct and indirect tests on human dermal fibroblasts (HDF) as per ISO 10993. The positive effect of GGMA patches on cell migration was assessed through a wound healing assay. The results highlighted that the patches are cytocompatible, speed up wound healing and can swell upon contact with the hydration medium and release TA and AA in a controlled way. Overall, the TA- and AA-loaded GGMA patches demonstrated suitable mechanical features; no cytotoxicity; and antioxidant, antimicrobial and wound healing properties, showing satisfactory potential for wound dressing applications. Full article

Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics and the emergence of antibiotic-resistant strains. In a previous study, a chitosan-based matrix crosslinked with tannic acid and loaded with gentamicin was reported. In this study, five different antibiotics (moxifloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole or linezolid) were loaded into these chitosan-based films, and their impact on the release behavior carefully assessed. Methods: The samples were characterized according to their thickness, swelling, and mass loss in phosphate-buffered saline (PBS), as well as by morphology using scanning electron microscopy (SEM) and optical phase contrast microscopy. Antibiotic release over time was quantified in PBS by high-performance liquid chromatography (HPLC). Antibacterial activity was investigated by disk diffusion test and antibiotic release over time. Finally, the cytotoxicity of the samples was assessed with human dermal fibroblasts. Results: The obtained results differed significantly, especially regarding the antibiotic release time and antibacterial activity, which varied from one day to six months, enabling classification of the films from burst/transient to prolonged release. The films also showed antibacterial features against bacteria mostly present in medical devices and displayed to be non-cytotoxic. Conclusions: In conclusion, it was demonstrated that the antibiotics structure significantly alters the release kinetics, and that by carefully selecting the antibiotic, the consequent release can be tuned. This approach yielded films that could be used for potentially-scalable release in antimicrobial coatings specific to medical devices, aiming to reduce biomaterial associated infections (BAIs). Full article