Search Results (2,395)

Chronic infected wounds are often characterized by persistent bacterial colonization, biofilm formation, excessive oxidative stress, and prolonged inflammation, which severely impair tissue regeneration. To address these challenges, a multifunctional wound dressing capable of antibacterial activity and microenvironment modulation was developed. In this study, amide-modified hyaluronic acid (HA-ADH) was used as the matrix, and a dynamic coordination network was constructed via Cu²⁺-hydrazide interactions to form an in situ HA-Cu hydrogel. Curcumin-loaded DSPE-PEG2000 micelles were further incorporated to obtain a pH-responsive composite hydrogel (HA-Cu/Cur). The prepared hydrogel exhibited a porous interconnected structure, along with favorable injectability, self-healing capability, tissue adhesiveness, moderate swelling, controllable degradability, and pH-responsive behavior under acidic conditions. In vitro antibacterial assays demonstrated that both HA-Cu and HA-Cu/Cur effectively inhibited the growth and biofilm formation of Escherichia coli and Staphylococcus aureus. The antibacterial activity was associated with disruption of bacterial morphology, depletion of intracellular ATP, and induction of reactive oxygen species, while HA-Cu/Cur showed enhanced performance in antibiofilm activity and oxidative stress-related effects compared with HA-Cu. Cytocompatibility studies revealed that the hydrogel extracts exhibited negligible cytotoxicity toward L929 fibroblasts and RAW 264.7 macrophages, while promoting fibroblast migration and significantly reducing the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide-stimulated RAW 264.7 cells, with HA-Cu/Cur showing a more pronounced anti-inflammatory effect. In summary, the HA-Cu/Cur hydrogel integrates the antibacterial and pro-healing properties of Cu²⁺ with the antioxidant and anti-inflammatory activities of curcumin. The hydrogel effectively inhibited the growth and biofilm formation of both E. coli and S. aureus, reduced the expression of TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages, and promoted fibroblast migration, demonstrating its potential as a multifunctional wound dressing for the management of infected wounds. Full article

Background: Bone tissue is a dynamic structure capable of continuous remodeling; however, its regenerative capacity is limited in critical-size defects, often requiring the use of bone grafting procedures. Available grafting materials present inherent limitations, highlighting the need for strategies that can enhance regenerative outcomes. Hyaluronic acid (HA) has been proposed as a promising adjunctive agent because of its biological properties, including anti-inflammatory and pro-angiogenic effects. Objective: To systematically evaluate the available clinical evidence regarding the effects of HA as an adjunct in bone regeneration procedures, including alveolar ridge preservation, ridge augmentation, and maxillary sinus elevation. Materials and Methods: A systematic search was conducted in the PubMed, ScienceDirect, Google Scholar, and Wiley Online Library databases for studies published within the last 10 years. Clinical studies involving adult patients were included if they evaluated the local application of HA, regardless of formulation, and reported quantitative clinical, radiographic, histological, or histomorphometric outcomes related to bone regeneration. Results: Of the 728 records initially identified, 10 studies met the eligibility criteria and were included in the qualitative synthesis. Discussion: Overall, the available evidence suggests that HA may positively influence bone regeneration outcomes. The most consistent benefits were observed in alveolar ridge preservation and ridge augmentation procedures, including increased new bone formation, improved bone density, enhanced bone maturation, and reduced dimensional bone loss. In contrast, findings regarding maxillary sinus augmentation were less consistent. Conclusions: HA appears to be a promising adjunct in bone regeneration procedures. However, the current evidence remains limited and is primarily based on clinical outcomes, providing insufficient mechanistic data to fully elucidate its biological effects. Further well-designed randomized controlled trials with standardized protocols are required before definitive clinical recommendations can be established. Full article

This single-center prospective observational study evaluated peri-procedural changes in circulating markers of endothelial glycocalyx injury in patients with chronic limb-threatening ischemia undergoing lower extremity endovascular treatment. Fifty patients (mean age 72.2 years; 56% with diabetes mellitus; 42% current smokers) underwent percutaneous transluminal angioplasty, most commonly involving the femoropopliteal segment and using 4F introducer sheaths. Serum concentrations of syndecan-1, heparan sulfate, and hyaluronic acid were measured using ELISA before and one day after the procedure. No significant differences were observed between baseline and post-procedural biomarker levels, with minimal median changes, overlapping interquartile ranges, and negligible paired effect sizes. Although individual biomarker trajectories demonstrated considerable interindividual variability, no consistent directional trend was identified. Furthermore, demographic and clinical factors, including age, sex, diabetes, and smoking status, as well as procedural variables such as stent implantation, sheath size, and intervention level, were not associated with biomarker changes in univariate or multivariable analyses. These findings suggest that contemporary endovascular revascularization is biologically well tolerated and does not induce detectable systemic endothelial glycocalyx disruption. Nevertheless, the interpretation of these findings is limited by the moderate sample size and single-center design of the study. In addition, syndecan-1, heparan sulfate, and hyaluronic acid are not exclusive markers of endothelial glycocalyx injury and may also reflect extracellular matrix turnover and tissue remodeling. Full article

Tremella fuciformis extract (TFE) is used in dermocosmetic formulations due to its moisturising, antioxidant, and skin-supportive properties. The present study compared the effects of commercial TFE and hyaluronic acid (HA) on selected functions of human dermal fibroblasts (HDF). The cells were treated with TFE at concentrations of either 200 µg/mL or 500 µg/mL, or with HA at a concentration of 500 µg/mL. The following parameters were the focus of the study: cell viability, DNA and collagen biosynthesis, prolidase activity, scratch-wound closure, and immunofluorescence of selected signalling- and extracellular matrix-related markers. The findings of this study demonstrate that neither TFE nor HA had any effect on HDF viability. TFE led to a significant increase in DNA biosynthesis at both concentrations, while HA had no significant effect. The synthesis of collagen was found to be considerably elevated by both HA and TFE500, with no such effect observed in the presence of TFE200. Prolidase activity was observed to be highest in the HA group and also elevated in the TFE500 group; however, these results should be regarded as descriptive due to the nature of the pooled-sample data. Immunofluorescence analysis revealed increased phosphorylated protein kinase B (p-AKT) fluorescence in images treated with TFE, while phosphorylated mechanistic target of rapamycin (p-mTOR) remained close to the control level. Higher levels of β1-integrin, Insulin-Like Growth Factor-I Receptor (IGF-1R), prolidase, and phosphorylated Extracellular Signal-Regulated Kinases (p-ERK1/2) fluorescence were also observed in selected groups. The mean scratch-wound closure was found to be highest for TFE500. Overall, TFE was found to be associated with DNA biosynthesis, whereas HA and TFE500 were found to enhance collagen biosynthesis. Further studies are required to confirm biological reproducibility and the mechanism. Full article

Background/Objectives: Intra-articular injections are used for temporomandibular disorders (TMDs) resistant to conservative treatment. However, many reviews assess injectable agents combined with arthrocentesis or other co-interventions, limiting interpretation of their standalone effects. This overview aimed to summarize meta-analytic evidence on standalone intra-articular injections for temporomandibular joint disorders. Methods: MEDLINE, BASE, and Europe PMC were searched on 29 March 2026. Systematic reviews with quantitative meta-analyses evaluating standalone intra-articular TMJ injections were included. Data regarding injectable substances, clinical indications, and outcome domains were extracted and synthesized descriptively. Results: Three systematic reviews with meta-analyses were included. The evidence addressed platelet-rich plasma, corticosteroids, sodium hyaluronate, and physiological saline. Reported indications included degenerative joint disease, osteoarthritis, internal derangement, and arthritis. All included agents were reported to be associated with pain reduction. Conclusions: Meta-analytic evidence on standalone intra-articular injections for TMDs remains limited and heterogeneous. Available data suggest potential benefits, mainly for pain reduction, but do not establish clear superiority of any agent. The potential therapeutic activity of physiological saline should be considered when designing future injection trials. Full article

Osteoarthritis (OA) is the most prevalent degenerative joint disease in both humans and companion animals, causing progressive cartilage destruction for which no curative treatment currently exists. Plasma rich in growth factors (PRGF) has shown chondroprotective effects in veterinary and preclinical models, but its efficacy is limited by the viscosity of synovial fluid and rapid degradation of growth factors within the joint. This study aimed to evaluate the effect of intra-articular co-administration of PRGF and urease-powered enzymatic nanobots on serum biomarkers of inflammation, oxidative stress, and cartilage metabolism in a rabbit (Oryctolagus cuniculus) full-depth chondral defect model (approval code: CEEA 2023-VSC-PEA-0242). Forty-one New Zealand White rabbits were allocated to a Control group (PRGF alone; n = 9 evaluable) or a Nanobots group (PRGF + nanobots; n = 24 evaluable). Twelve serum biomarkers were measured at baseline and days 28, 56, and 84. The Nanobots group showed markedly elevated serum hyaluronic acid at all timepoints (p < 0.006), significantly lower type II collagen cleavage neoepitope at day 28 (p = 0.018), persistently lower ferric reducing ability of plasma (p < 0.003), and higher C-reactive protein at days 56 and 84 (p < 0.035). These results provide preliminary in vivo evidence that urease-powered nanobots produce a distinct biomarker profile when combined with PRGF in a rabbit chondral defect model, with potential translational relevance for veterinary orthopedic therapy. Full article

The local twitch response (LTR) elicited during ultrasound-guided fascial hydrorelease (FHR) is conventionally attributed to dysfunctional motor endplates. Recent observational data from a companion study suggest that LTR events may occur preferentially within stacking fascia—a histologically defined multilayered, densified region of deep fascia—at sites not directly attributable to motor endplate excitation. We propose the Fascial Capacitor Model: stacking fascia can be conceptually modeled as a multilayer biological capacitor in which collagen sublayers may act as electrodes and the interposed densified hyaluronic-acid (HA)-rich loose layer may act as the dielectric, with the LTR hypothesized to reflect a transient electrophysiological discharge when a needle bridges its layers. This biophysical model is grounded in the established molecular and histological architecture of human deep fascia, and the analogy is intended as one of structural isomorphism, rather than complete functional equivalence with engineered capacitor devices. Each premise is independently supported by the primary literature from at least eight research lines spanning roughly seventy years. The apparent gap between estimated bulk discharge voltages and motor neuron threshold is addressed by reconsidering needle-tip geometry and stimulation modality, anchored by the ±6 V triboelectric measurements. The pathological extension of the RC time constant in densified fascia—lengthening by several orders of magnitude and estimated to reach the millisecond range—is supported by empirical evidence from fibrotic extracellular matrices in other connective tissues, while tissue-specific in vivo measurements in fascia remain a future task. The model is positioned as the immediate-phase complement to the Fascial Memory Reset Hypothesis, provides a candidate mechanistic interpretation for intra-procedural symptom relief—an as-yet unquantified clinical observation awaiting formal patient-reported outcome (PRO) measurement in a prospective trial—and yields falsifiable predictions. A direct empirical validation program using insulating-needle recording of spontaneous electrical activity (SEA) is in preparation at the corresponding author’s institution. Full article

Acne is a common inflammatory skin condition that significantly impacts quality of life. Standard treatments often cause skin irritation or contribute to antibiotic resistance. Cannabidiol (CBD) has demonstrated anti-inflammatory and sebum-regulating properties; however, its application is limited by poor solubility and stability. This study investigated the physicochemical properties of a CBD-loaded hyaluronic acid–graft-poly(N-isopropylacrylamide) nanogel (Hy-CBD). The biological activities of Hy-CBD, including its anti-inflammatory and antioxidant effects, were also evaluated. In addition, an exploratory clinical study was conducted to assess the safety and efficacy of the formulation in 22 Asian participants with inflammatory acne. In this open-label, non-randomized study, participants applied the gel twice daily for seven days. Assessments of skin tolerance, lesion size, redness, and pigmentation were performed at baseline, Day 2, and Day 7 using clinical examination and imaging analysis. The Hy-CBD gel was clinically tolerated, with no evidence of comedogenic or acnegenic potential. By Day 7, inflammatory lesion size was reduced by 46%, with significant improvements in redness and post-inflammatory pigmentation. All participants reported a subjective reduction in acne severity and expressed satisfaction with the treatment outcomes. These findings suggest that the Hy-CBD gel is a safe and promising delivery system for acne management. Nevertheless, larger randomized controlled studies are required to validate these preliminary findings. Full article

Polysaccharide–peptide conjugates are modular biomaterials that combine hydrated carbohydrate frameworks with peptide domains capable of mediating molecular recognition, degradability, antimicrobial activity, and biological signaling. In this review, we discuss how covalent, bioorthogonal, and enzymatic conjugation strategies regulate peptide density, orientation, accessibility, and stability within polysaccharide-based matrices. These chemical choices are analyzed in relation to network architecture, viscoelasticity, ligand presentation, degradation behavior, and cell–material interactions. Representative systems based on hyaluronic acid, alginate, chitosan, dextran, cellulose, and glycosaminoglycans are examined to illustrate how peptide functionalization can transform otherwise passive scaffolds into adhesive, degradable, antimicrobial, or therapeutically responsive platforms. We further highlight dynamic and enzyme-responsive materials, localized drug delivery systems, antimicrobial coatings, and antibiofilm interfaces as key biomedical applications of these conjugates. The review also addresses translational challenges associated with structural heterogeneity, stability, immunogenicity, sterilization, batch-to-batch reproducibility, and clinical feasibility. Taken together, the evidence discussed here indicates that the performance of polysaccharide–peptide conjugates depends on reproducible structure–function relationships linking conjugation chemistry, macromolecular architecture, and biological activity under application-relevant conditions. Full article

Background/Objectives: Ultrasound-guided fascial hydrorelease (FHR) occasionally elicits a brief localized contraction (“local twitch”) at the moment the needle tip contacts a fascial layer; the anatomical basis of this reaction has not yet been systematically characterized. To examine local twitch occurrence relative to stacking fascia (yes/no) at the needle tip (primary outcome), as well as the anatomical distribution and per-video capture rate (secondary outcomes). Methods: We retrospectively analyzed 11,205 ultrasound videos from a single pain clinic (October 2015–March 2026). Twitches were identified by prospective clinical observation and computational screening (frame-difference-based Profile Match classifier; 417 candidates over 30 review rounds). The stacking fascia status was independently determined by two FHR-experienced clinicians, with discordant cases jointly adjudicated. Results: Inter-rater agreement was 86/90 (95.6%; 95% CI 89.0–98.8%); one case was reassessed, deemed to not be a twitch, and excluded. In the final cohort (n = 89), local twitches occurred at stacking fascia in 89/89 (100%; 95% CI 95.9–100%). Events were concentrated in gluteal/pelvic (51%) and lumbar paraspinal (29%) regions, with a per-video capture rate of 0.98% (110/11,205; 95% CI 0.81–1.18%). Conclusions: Local twitches during ultrasound-guided FHR essentially always coincide with the needle tip lying within stacking fascia, identifying this as the structural locus within this cohort. This figure represents inclusion-criterion-bound selectivity within the twitch-positive subset, not the positive predictive value of stacking fascia for twitch occurrence. Full article

Daunomycin (daunorubicin) is one of the most clinically significant anthracyclines used in chemotherapy, and its efficient production remains a major objective for biotechnological researchers. Industrial manufacturing relies on the fermentation of Streptomyces peucetius and Streptomyces coeruleorubidus, which produce daunomycin as a secondary metabolite under controlled conditions. This review will focus on the methods to enhance the total efficiency of biotechnological production, from upstream biosynthesis to downstream processing. Given the complexity of the daunomycin biosynthetic pathway in Streptomyces spp., substantial progress has been made in strain improvement to increase yield, metabolic robustness, and process stability. Advances in classical mutagenesis, pathway engineering, regulatory network modulation, and precursor supply optimization, along with rational medium design and advanced process control, have led to substantial increases in product titers and productivity. At the same time, innovations in downstream processes, such as extraction, purification and process integration, have increased recovery efficiency, product quality, and economic feasibility. With improvements in the production process, novel drug delivery modalities have been developed (e.g., drug carriers based on erythrocytes, drug nanocarriers based on hyaluronic acid) with increased efficiency and lower systemic toxicity. These developments indicate an evolution from pathway-level engineering to industrial-scale manufacturing and clinical application, underlining the evolution of daunomycin research and biotechnological production. Full article

Background and Objectives: Knee osteoarthritis (KOA) and other degenerative chondropathies are major causes of pain and disability. When core conservative treatments are insufficient, intra-articular hyaluronic acid (HA) and platelet-rich plasma (PRP) are commonly used as adjunctive options, although evidence remains difficult to interpret because of heterogeneity in patients, products, preparation protocols, and treatment schedules. This exploratory retrospective study described short-term clinical outcomes after two standardized intra-articular protocols, hybrid HA and autologous PRP, in a real-world outpatient physiatry setting. Materials and Methods: This monocentric retrospective study included 40 treated knees (19 HA, 21 PRP) from 31 unique patients at the Policlinico di Bari between October 2022 and November 2024. The HA group received two injections of a hybrid high-/low-molecular-weight HA formulation, whereas the PRP group received three injections of autologous PRP. Outcomes were pain intensity, assessed by the Numerical Rating Scale (NRS), and function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), from baseline to end-of-cycle follow-up. Results: Both groups showed short-term clinical improvement. Mean NRS scores decreased from 6.26 to 2.26 in the HA group and from 6.76 to 2.29 in the PRP group, with no significant between-group difference in change from baseline (p = 0.509). WOMAC improved by 25.42 ± 20.39 points in the HA group and 20.19 ± 16.18 points in the PRP group (p = 0.372). In the main regression analysis, treatment type was not a significant predictor of outcome; unadjusted and age-/sex-adjusted WOMAC sensitivity models suggested a possible HA advantage that was not retained after full adjustment. Conclusions: In this small exploratory cohort, both protocols were associated with short-term improvements, without definitive fully adjusted evidence of between-group superiority. These findings should not be interpreted as evidence of equivalence or definitive comparative efficacy. Full article

The periorbital region represents one of the most challenging anatomical sites in aesthetic medicine due to its thin dermis, complex vascularity, and susceptibility to oedema and contour irregularities. While hyaluronic acid (HA) fillers remain the gold standard for volumetric correction, their limitations in skin quality enhancement and risk of complications such as Tyndall effect and malar oedema have driven interest in regenerative alternatives. Polynucleotides (PN), particularly polydeoxyribonucleotides (PDRN), have emerged as bioactive agents capable of promoting dermal remodelling, angiogenesis, and anti-inflammatory responses. This review critically evaluates current evidence comparing PN and HA in periorbital rejuvenation, integrating mechanistic insights, clinical outcomes, and safety considerations. While HA remains superior for structural correction, PN demonstrates consistent improvements in dermal quality parameters, including elasticity, hydration, and fine rhytids, with a favourable safety profile. However, heterogeneity in study design, product formulation, and outcome measures limits the ability to draw definitive conclusions. Future research should prioritise standardised protocols, long-term follow-up, and direct comparative trials to establish optimal treatment algorithms. Full article

Background: Acne vulgaris affects up to 80% of individuals aged 11–30 years and frequently results in permanent scarring with significant psychosocial impact. This prospective single-arm case series evaluated the safety and high-frequency ultrasound-assessed morphological changes in a combined protocol integrating subcision, PEGDE-crosslinked hyaluronic acid supplemented with calcium hydroxyapatite (CaHA), and fractional 1470 nm diode laser therapy in patients with facial atrophic acne scars. Methods: Twenty patients (aged 18–42 years, Fitzpatrick phototypes I–II) with moderate-to-severe atrophic acne scars underwent subcision of fibrotic adhesions using a 22G cannula combined with a single subcutaneous injection of 2 mL PEGDE-crosslinked hyaluronic acid with CaHA microparticles on day 0, followed by two sessions of fractional 1470 nm diode laser therapy on days 7 and 28. Scar depth and diameter were assessed using high-frequency ultrasound (48 MHz) at baseline and on days 28, 49, 77, and 139. Results: All participants completed the protocol without serious adverse events. High-frequency ultrasound demonstrated progressive reductions in mean scar depth (from 0.35 to 0.05 mm; −86%) and scar diameter (from 4.27 to 1.06 mm; −75%) by day 139, with reductions continuing beyond the active treatment phase. In linear mixed-effects models accounting for within-patient clustering of the two lesions assessed per participant, the reductions in both depth and diameter were statistically significant at every follow-up timepoint relative to baseline (all p < 0.001). These ultrasound findings were not corroborated by a control group, blinded assessment, validated clinical grading, or patient-reported outcomes. Conclusions: In this single-arm case series, the combined subcision, PEGDE-crosslinked HA–CaHA filler, and fractional 1470 nm diode laser protocol was well tolerated and associated with progressive, sustained reductions in high-frequency ultrasound-measured scar depth and diameter. As an uncontrolled, unblinded study without validated clinical grading or patient-reported outcomes, these findings are preliminary and require confirmation in larger, controlled trials. Full article

Diabetic foot ulcers (DFUs) are among the most severe complications affecting diabetic patients, and dressing therapy is one of the standard treatments for DFUs. However, traditional dressings are inadequate for addressing the complex microenvironment of DFUs. Consequently, advanced natural polymer-based dressings have attracted extensive research attention in diabetic foot care due to their biocompatibility, low immunogenicity, and biodegradability. These natural polymer materials include collagen, gelatin, chitosan (CS), hyaluronic acid (HA), alginate, and cellulose. This review systematically analyzes the pathophysiological mechanisms underlying the difficult healing of DFUs and the advantages of natural polymer-based dressings in diabetic wound healing, highlights preclinical studies, and synthesizes evidence from clinical research. Moreover, we pinpoint the challenges associated with these dressings and propose future directions for the improvement of diabetic wound care. Full article