Search Results (2,341)

Hyaluronic acid (HA) hydrogels have attracted increasing interest for biomedical applications due to their tunable properties and biocompatibility. Methods: In this study, hyaluronic acid HA-based hydrogels were developed using two distinct crosslinking strategies: physical crosslinking through poly(vinyl alcohol) (PVA) incorporation and covalent crosslinking via DCC/NHS-mediated reactions. Piroxicam (Px) was included as a model drug to evaluate the drug delivery potential of the resulting systems. The hydrogels were characterized in terms of morphology, swelling behaviour, adhesion, enzymatic degradation, drug release, and in vitro cytocompatibility. Results: The results indicate that formulation parameters significantly influence the overall performance of the systems. PVA-containing hydrogels exhibited higher swelling capacity and improved adhesive properties, while covalently crosslinked networks showed reduced swelling and enhanced structural stability and resistance to enzymatic degradation. Drug release profiles were dependent on network structure, with more compact systems displaying slower release behaviour. In vitro assays suggested that the developed hydrogels are cytocompatible and that drug incorporation influences both release kinetics and cellular response. However, it should be noted that the biological evaluation was performed under simplified in vitro conditions, which primarily reflect specific aspects such as cell viability and migration. Conclusions: This study provides a comparative analysis of physical and covalent crosslinking strategies within a HA platform and highlights how formulation variables influence key physicochemical and biological properties. These findings contribute to the rational design of HA-based hydrogels, although further studies are required to establish their performance in more complex biological environments. Full article

Microneedle systems represent a promising minimally invasive approach for transdermal drug delivery; however, their performance strongly depends on the composition and mechanical properties of the polymer matrix. The aim of this study was to select an optimal polymer composition for the fabrication of dissolving microneedle arrays produced by the mold casting method. The study focused on evaluating mechanical strength, dissolution behavior, and penetration efficiency of different polymer systems. Microneedle matrices were fabricated using polyvinylpyrrolidone (PVP K-30), methylcellulose, sodium alginate, and hyaluronic acid at various concentrations, alone and in combination. No active pharmaceutical ingredient (API) was incorporated; the study was performed using blank polymeric systems intended for subsequent drug loading. The microneedles were manufactured using 3D-printed and silicone molds. Their performance was evaluated by in vitro dissolution testing, pH measurement, penetration studies in gelatin gel and Parafilm M models, and mechanical compression testing. Monopolymer systems demonstrated either rapid dissolution with insufficient mechanical strength or improved strength at the expense of prolonged dissolution time. Combined polymer formulations showed superior structural uniformity and balanced performance. In particular, the system containing 5% PVP K-30 and 10% sodium alginate demonstrated the best overall characteristics, achieving high penetration efficiency (up to 96%), uniform dissolution (78%), and appropriate dissolution time (8.5 ± 0.5 min). Addition of hyaluronic acid further improved structural uniformity and handling properties. The results indicate that composite polymer matrices provide an optimal balance between mechanical stability, penetration ability, and dissolution rate. The formulation consisting of 5% PVP K-30 and 10% sodium alginate was identified as the most promising base for further development of drug-loaded dissolving microneedle systems. Full article

Acne is a prevalent chronic inflammatory skin disorder with a high recurrence rate, in which Propionibacterium acnes (P. acnes) plays a key pathogenic role by colonizing subepidermal pilosebaceous units. The stratum corneum limits drug penetration, rendering conventional topical therapies ineffective. Herein, we report a detachable sustained-release microneedle system named Bacitracin@Hyaluronic Acid–Zein Microneedle (Bac@HA-ZMN) for localized antibacterial delivery in acne therapy. This microneedle patch consists of a dissolvable HA base and zein-based indwelling microneedle tips loaded with bacitracin (Bac) against P. acnes. Mechanical testing showed an average fracture force of 1.6 N per needle tip (n = 100), sufficient for skin insertion. The needle tips enabled Bac delivery to a depth of approximately 500 μm. In vitro transdermal studies demonstrated a cumulative release of 76.1% within 96 h, significantly higher than that of the control group (14.2%). In a murine acne model, the Bac@HA-ZMN treatment group showed a significantly smaller lesion area than the control group, and the immunohistochemical positive expression areas of the inflammatory factors IL-8, MMP-2, and TNF-α were reduced to 0.79%, 4.12%, and 2.14%, respectively, which was caused by the inhibitory effect of Bac on P. acnes. These results demonstrated Bac@HA-ZMN as a promising localized, sustained antibacterial delivery platform for acne treatment. Full article

Laser surface texturing (LST) was used to process circular patterns on silicon nitride (Si₃N₄) ceramic. The surface wettability of un-textured and textured Si₃N₄ ceramic was studied. It was found that all samples were hydrophilic. The hydrophilicity of the textured Si₃N₄ ceramic with a smaller interval was weaker. Effect of the interval on the tribological performance of Si₃N₄ ceramic was investigated under different reciprocating frequencies. As the reciprocating frequency increased, the coefficient of friction (COF) of Si₃N₄ ceramic showed an overall upward trend. And the COFs of textured Si₃N₄ ceramic were higher. At the reciprocating frequency of 0.5 Hz, the COFs of textured samples with different intervals were relatively close. At higher reciprocating frequency, the difference in COF gradually increased. This can be attributed to the change in lubrication state that occurs during the frictional process. Debris and plough were found at surface of all samples, and the original surface was cleaner. The surface damage of textured samples was more severe than that of un-textured samples. EDS analysis on the wear area was performed. The wear rate of the frictional pair at the interval of 250 μm was higher. It was consistent with the more significant wear marks on the surface of the Si₃N₄ ceramic at this interval. There were significant differences in the frictional process between un-textured and textured samples. For the un-textured surface, the debris was mainly concentrated at the edges of the friction trajectory. In contrast, textured patterns had the function of storing lubricant, while also generating micro-shear effects on debris and improving the status of lubrication, resulting in more complex frictional process. Full article

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN providing hydration and skin support, and niacinamide offering anti-inflammatory and antioxidant properties. A prospective, open-label clinical investigation was conducted on 42 female subjects (mean age 45 ± 1 years, Fitzpatrick skin phototypes II-V) to assess skin elasticity, hydration, and mild skin depression correction following cheek area injections. Efficacy was measured using the Global Aesthetic Improvement Scale (GAIS), Antera 3D^® (texture), Cutometer^® (elasticity/firmness), Corneometer^® (hydration), and Dermascan^® (density/thickness) devices at baseline (D0), week 2 (W2/D14), and week 6 (W6/D42). GAIS values showed significant overall facial improvement (p < 0.001) by both investigators and subjects, where 100% of subjects rated their appearance as improved immediately post-injection (D0), with sustained improvements at D42. Objective measurements revealed significant improvements in skin texture (reduced roughness), elasticity, firmness, hydration (p < 0.001), density, and thickness, demonstrating the combined benefits of the HA, PN, and niacinamide blend. Injection site reactions, primarily mild and transient, were reported immediately post-injection. Investigators and subjects reported high satisfaction with the product’s ease of use and aesthetic outcomes. Globally, HYDRAGEL A2, leveraging the established benefits of HA, PN, and niacinamide, was well-tolerated and effectively enhanced facial skin quality, demonstrating significant and sustained improvements in monitored skin parameters. The study concludes that this combination of ingredients, formulated in HYDRAGEL A2, provides a well-tolerated approach associated with improvements in skin quality. Full article

The red alga Kappaphycus alvarezii is a rich source of bioactive compounds with potential applications in the cosmetic industry. This study aimed to characterize a cosmetic serum containing K. alvarezii and evaluate its immediate moisturizing effect on the skin. A randomized, triple-blind, parallel-group clinical trial was conducted with 28 healthy participants, allocated 1:1 to receive either a control formulation with hyaluronic acid or a test formulation with K. alvarezii. The formulations were assessed for stability over 60 days using organoleptic, microbiological, pH, and rheological analyses. Mechanical and bioadhesive properties were assessed using a texture analyzer, while the water content of the stratum corneum on the palms and backs of the hands was measured in vivo using a Corneometer^® CM 825 (Courage & Khazaka Electronic GmbH). Both formulations showed similar stability and rheological behavior. Texture analysis indicated comparable compressibility and elasticity, with a slight reduction in bioadhesive strength for the test formulation. In vivo results demonstrated a moisturizing effect for both formulations, with a significant increase in palmar hydration 60 min after application of the K. alvarezii serum. These findings indicate that the formulation containing K. alvarezii can improve short term skin surface hydration; potential contributions of film formation and barrier modulation remain hypothetical and were not directly assessed in this study. Full article

Cutaneous leishmaniasis remains a major therapeutic challenge due to drug toxicity, resistance, and limited efficacy against intracellular parasites. This study evaluated the therapeutic potential of nanoformulated Walterinnesia aegyptia (WA) venom using hyaluronic acid-based (WA-HA) and silver-based (WA-Ag) nanoparticles. Nanoparticles were synthesized and characterized by scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antipromastigote activity of crude WA venom was assessed by MTT assay, and apoptosis induction was analyzed using Annexin V-FITC/propidium iodide flow cytometry. In vivo efficacy was evaluated in BALB/c mice infected with Leishmania major, with outcomes assessed by lesion progression, biochemical markers, histopathology, and PCR-based parasite detection. WA venom exhibited potent dose-dependent cytotoxicity (IC50 = 26.73 µg/mL) and induced predominantly apoptotic cell death. In vivo, nanoformulated WA significantly enhanced therapeutic outcomes compared with crude venom, with WA-HA achieving near-complete lesion resolution comparable to Amphotericin B. Treatment also reduced parasite burden, normalized liver enzyme levels, and restored hepatic and splenic architecture. These findings demonstrate that nanocarrier-based delivery markedly improves the therapeutic performance and systemic safety of WA venom, highlighting its potential as a promising nanotherapeutic strategy for cutaneous leishmaniasis. Full article

The aim of this study was to identify and examine materials that have a long history of use in folk medicine and exhibit biological activity but have not been fully utilized. This study evaluated the reactivity of Japanese maca powder in cultured human dermal cells subjected to aging stress (UV irradiation, AGE treatment, or H₂O₂ treatment). The mRNA levels of three stress parameters (collagen, elastin, and hyaluronic acid synthase) were measured using quantitative reverse transcription polymerase chain reaction. The activity of a prototype Japanese maca powder sample was compared with that of samples subjected to fermentation, room-temperature enzyme, and rapid freeze-drying treatments. Inhibitory effects on reactive oxygen species (ROS) were measured, and the expression of genes involved in senescent cell removal (JAG1) and regeneration promotion (EGF) was examined. Finally, the expression of molecules involved in senescent cell phagocytosis (STAB1) and stem cell phagocytosis signaling and regeneration promotion (FGF2) in macrophages was evaluated. The four types of maca samples altered the mRNA levels of the three stress parameters, conferred resistance to various aging stresses, and delayed suppressed intracellular ROS accumulation. These findings suggest that Japanese maca may help to protect skin cells from age-related stress. Full article

Surgical intervention is a primary treatment for osteosarcoma, often resulting in a tumorous bone defect with an irregular shape. Postoperative management is essential to minimize tumor recurrence risks and promote bone regeneration. To address these issues, we developed a multifunctional injectable, rapidly photo-curable hydrogel composed of gelatin methacryloyl/carboxymethyl chitosan/hyaluronic acid (GelMA/CMCS/HA), modified with vanadium-doped mesoporous bioactive glass (VMBG). The exceptional injectability enables seamless adaptation to irregular bone defects, offering a significant advantage over preformed implants, while the rapid photocurability of the hydrogel ensures stable fixation within minutes, thereby reducing potential risks during surgery. Furthermore, this platform exhibits dual therapeutic efficacy, characterized by antitumor activity and osteogenic induction. In vitro assessments demonstrated that V(V)/V(IV) valence cycling-driven ROS generation mediated its potent antitumor efficacy. Additionally, concurrent enhancement of alkaline phosphatase activity and osteogenic marker expression validated its osteogenic potential. The CMCS incorporation promoted healing at the defect site, while the HA addition created binding sites for cell adhesion and growth, thereby improving scaffold bioactivity. Collectively, this study presents the development and validation of a multifunctional GelMA/CMCS/HA hydrogel, highlighting its dual capability for bone regeneration and tumor suppression within tumor-associated bone microenvironments. Full article

In this study, a hierarchical design strategy is introduced for tuning the release of rosmarinic acid (RA) from electrospun poly(L-lactide) (PLA) fibrous materials via surface engineering with chitosan/hyaluronic acid (Ch/HA) polyelectrolyte complexes (PECs). RA was selectively incorporated within the fiber bulk, the PEC coating, or both, enabling control over its spatial distribution. The PEC coating, formed by sequential dip coating, was shown to act as a diffusion-regulating layer with a dual role—either retarding RA release or promoting rapid initial release when functioning as a surface-associated reservoir. As a result, the release kinetics could be systematically tuned depending on the coating architecture and RA localization. Thorough characterization confirmed successful coating formation, enhanced surface hydrophilicity, and improved mechanical performance. All RA-loaded materials retained high antioxidant activity and exhibited pronounced antibacterial and antifungal effects against Staphylococcus aureus, Escherichia coli, and Candida albicans. This work introduces PEC-modified electrospun systems as a versatile platform for the rational design of multifunctional fibrous biomaterials with controlled release profiles, with potential applications in wound healing and drug delivery. Full article

Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such as CD44 and RHAMM, with outcomes highly dependent on molecular weight, degradation state, and matrix context. Recent advances in chemical modification and crosslinking strategies have enabled the development of HA-based hydrogels, nanofibers, and composite systems with tunable mechanics and degradation profiles, supporting applications in bone, cartilage, vascular, and skin regeneration, as well as in emerging platforms such as 3D bioprinting and nanomedicine. However, inconsistent biological responses and limited clinical translation remain key challenges. This review integrates current understanding of HA synthesis, physicochemical properties, degradation, and receptor-mediated signaling, and establishes a mechanistic framework linking molecular characteristics, matrix mechanics, and cell responses. Building on this framework, we outline design strategies for multifunctional HA composites, advanced biofabrication approaches, and receptor-targeted systems, providing a basis for the rational engineering of next-generation HA-based biomaterials with improved translational potential. Full article

Polydeoxyribonucleotide (PDRN) activates the adenosine A2A receptor (A2AR), triggering anti-inflammatory signaling and providing essential nucleotides for the salvage pathway, thereby helping bypass metabolic bottlenecks and promoting tissue repair. Combining PDRN with biochemical agents and physical stimuli represents a significant shift in medical treatment, moving from monotherapy to an integrated, multi-target regenerative approach. These combinatorial strategies effectively address the limitations of PDRN, such as its rapid degradation and diffusion, by simultaneously meeting the structural, metabolic, and signaling needs of injured tissues. The mechanism of action for PDRN involves a synergistic effect with hyaluronic acid, amplification of growth factors (e.g., Platelet-Rich Plasma (PRP), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF)), and enhancements from extracorporeal shockwave therapy (ESWT) and lasers. This results in a notable acceleration of the repair process for chronic wounds, musculoskeletal disorders, and neurological injuries. As intelligent delivery systems like responsive hydrogels and sustainable L-PDRN production continue to advance, these synergistic protocols are poised to redefine global standards of care in regenerative medicine and esthetic dermatology. Future clinical success will hinge on the standardization of sequence-specific protocols and large-scale validation to ensure long-term safety and efficacy. Full article

Protein-stabilized high-internal-phase Pickering gel-like emulsions (HIPGEs) have gained broad attention in the food industry and functional food sectors. Polyphenol–protein synergy is a common strategy to improve gel-like emulsion stability, yet issues such as insufficient interfacial viscosity persist, leading to poor long-term stability. Therefore, this study employed ovalbumin (OVA)-tea polyphenol (TP) as a composite model and introduced strongly negatively charged hyaluronic acid (HA) to construct a ternary Pickering gel-like emulsion with enhanced interfacial viscosity. We investigated the microstructure, physicochemical properties, stability mechanism, and simulated digestion behavior of the system. Results show that HA interacts with proteins and polyphenols via hydrogen bonding, strengthening the hydrogen-bond network and markedly improving gel-like emulsion stability. Moreover, HA stabilizes the oil–water interface by enhancing the viscoelasticity of the system. At 0.8% HA, centrifugal stability reached 99.52%, rheological properties were optimal, and droplets were more uniform and tightly packed. In vitro digestion revealed that 0.8% HA increased the final retention of lutein to 35.16% and reduced free fatty acid release to 0.31 μmol, demonstrating excellent protective and controlled-release potential. This study confirms that HA can significantly improve the stability and digestively controlled release of OVA-TP Pickering gel-like emulsions, providing theoretical support for polysaccharides in enhancing protein–polyphenol composite Pickering systems. Full article

Background: To investigate whether coating xenogeneic bone grafts with hyaluronic acid influences early osteogenic and fibrotic marker expression in vitro. Methods: Three xenograft materials were evaluated, including one hyaluronic acid-coated product and two uncoated deproteinized bovine bone mineral products, all commercially available. Human osteoblast-like cells (U2OS) and bone marrow stromal cells (HS5) were cultured with material extracts. Proliferation was assessed using XTT assay at 24 and 48 h. Cell adhesion was evaluated through fluorescence microscopy. Osteogenic markers (RUNX2, COL1A1) and fibrotic markers (COL3A1, TGF-β3) were quantified using quantitative real-time PCR. Statistical analysis employed one-way ANOVA with Benjamini–Krieger–Yekutieli (BKY) two-stage FDR correction for datasets that met the normality assumption, and the Kruskal–Wallis test with Dunn’s post hoc test for non-normally distributed data (HS5 XTT assay). Pairwise comparisons were restricted to each xenograft group versus the untreated control; an adjusted p-value < 0.05 was considered statistically significant. Results: At 48 h, the HA-coated xenograft (Xeno1) showed the highest mean metabolic activity in U2OS cells (0.538 ± 0.056) compared with the uncoated Xeno2 (0.450 ± 0.120) and Xeno3 (0.439 ± 0.073); however, after FDR correction no statistically significant differences were observed between groups. The coated material was associated with upregulation of early osteogenic markers, 2.61-fold RUNX2 upregulation (p = 0.01) compared to untreated cells. Both coated and uncoated xenografts demonstrated equivalent suppression of fibrotic markers in HS5 cells, reducing COL3A1 by 92.7% (p = 0.001) and TGF-β3 by 92.1% (p = 0.001). Conclusions: These exploratory in vitro findings suggest that HA coating may enhance early osteogenic marker expression. The observed effects on stromal markers warrant further investigation using primary cells, additional fibrotic endpoints (e.g., TGF-β1, ACTA2), and in vivo models before translational conclusions can be drawn. Full article

In this study, a hyaluronic acid (HA)-coated glabridin nanoemulsion was developed for enhanced macrophage uptake using the phase inversion temperature (PIT) method. The optimized cationic nanoemulsion consisted of a 10% w/w 60:40 peppermint oil:virgin coconut oil ratio, 10% w/w Cremophor RH40, 1% w/w cetyltrimethylammonium bromide, and 1% w/w ethanol. It exhibited a small droplet size, narrow size distribution, and positive zeta potential. Molecular dynamics simulations supported the experimental results, showing that systems containing a cosurfactant formed smaller droplets than those without a cosurfactant, particularly when ethanol was used as the cosurfactant. A concentration of 0.15% w/w HA solution at a 1:10 nanoemulsion–HA ratio yielded favorable characteristics, including a small droplet size (69.98 ± 0.48 nm), narrow size distribution (0.30 ± 0.00), and negative zeta potential (−23.00 ± 2.08 mV). Transmission electron microscopy image confirmed the presence of HA coating at 0.15% w/w. The incorporation of glabridin stabilized the droplet size (67.63 ± 0.33 nm) and polydispersity index (0.36 ± 0.01) but slightly decreased the absolute zeta potential (−10.83 ± 1.91 mV), whereas the entrapment efficiency was 91.65% ± 1.52% w/w. The nanoemulsion exhibited good physicochemical stability after storage at 40 °C for 6 months. HA coating enhanced the cellular uptake of the nanoemulsion into macrophage cells. The HA-coated glabridin nanoemulsion significantly inhibited the production of reactive oxygen species and nitric oxide and it also demonstrated low cytotoxicity. These findings indicated the potential of the PIT method to produce HA-coated glabridin nanoemulsion as a receptor-mediated delivery system for treating inflammation. Full article