Search Results (131)

Background: The combination of polynucleotides and hyaluronic acid with bovine bone grafts in maxillary sinus lift procedures appears to be a promising strategy to enhance bone regeneration. This study aimed to analyze implant osseointegration, bone repair and sinus mucosa integrity using Bio-Oss^® and Hyaluronic Acid-Polynucleotide Gel (Regenfast^®) in maxillary sinus augmentation in rabbits. Methods: Sinus floor elevation was performed in 12 rabbits, with one implant placed per sinus simultaneously. In the control group, sinuses were grafted with deproteinized bovine bone mineral (Bio-Oss^®) alone; in the test group, Bio-Oss^® was combined with Regenfast^®. Two histological slides were obtained per sinus after 2 weeks (six animals) and 10 weeks (six animals): one from the grafted area alone (non-implant sites), and one from the implant site. Primary outcome variables included the percentage of newly formed bone, the extent of implant osseointegration, and the number of sinus mucosa perforations caused by contact with graft granules. Results: After 10 weeks of healing, the test group showed a significantly higher percentage of new bone formation (37.2 ± 6.7%) compared to the control group (26.8 ± 10.0%; p = 0.031); osseointegration extended to the implant apex in both groups; fewer sinus mucosa perforations were observed in the test group (n = 5) than in the control group (n = 14). Conclusions: The addition of Regenfast^® to Bio-Oss^® granules promoted enhanced bone regeneration within the elevated sinus area and was associated with a lower incidence of sinus membrane perforations compared to the use of Bio-Oss^® alone. Full article

The biological complexity of sarcopenia presents a major challenge for therapeutic intervention due to the wide range of degenerative changes it induces in skeletal muscle. This study demonstrates the potential of liposomal controlled release systems to address these challenges by combining two bioactive agents with complementary actions: caffeine (CAF), encapsulated in DMPC-based liposomes, and hyaluronic acid methacrylate (HAMA), encapsulated in DOPC-based liposomes. A hybrid system was also developed to deliver both substances simultaneously, aiming to restore tissue function through combined metabolic, anti-inflammatory, and regenerative effects. The liposomes exhibited nanoscale dimensions, spherical morphology, and intact membrane structure, as confirmed by electron microscopy. DLS analysis indicated good colloidal stability and monodisperse size distribution across all formulations, with improved stability observed in the hybrid system. Drug release studies showed a time-dependent profile, with HAMA releasing rapidly and CAF releasing gradually, supporting a dual-action therapeutic approach tailored to the multifactorial pathology of sarcopenia. The biological assays, performed in an established in vitro sarcopenia model, revealed the potential of liposomes co-delivering caffeine and HAMA to mitigate oxidative stress, preserve mitochondrial function, and reduce apoptosis in H₂O₂-damaged myotubes. Full article

The hyperglycemic microenvironment in diabetic wounds predisposes them to bacterial infections, sustains chronic inflammation, and hinders therapeutic efficacy. In this study, antibiotic-loaded fast-crosslinked hybrid nanogel wound dressings (florfenicol nanogels) based on Schiff’s base bond were obtained through N, O-carboxymethyl chitosan (N, O-CMCS) and oxidized hyaluronic acid (OHA). The successfully prepared florfenicol N, O-CMCS/OHA nanogels exhibited obvious pH- and HAase-responsiveness release, which allowed it to quickly release florfenicol at infected wounds to exert on-demand antibacterial activity, as well as accelerate diabetic bacterial-infected wound healing. The nanogel dressings showed excellent antibacterial activity by destroying the bacterial cell membrane and wall. More specifically, the glucose oxidase in the dressings can catalyze the breakdown of high-concentration glucose, generating abundant ROS that directly cause cellular damage. According to the results of wound healing, the dressings showed satisfactory anti-inflammatory and therapeutic effects for the full-thickness mouse skin defect wounds. The nanogel dressings are anticipated to be excellent wound dressings to synergistically overcome the theraputic difficulty of diabetic bacterial wounds. Full article

Implant–prosthetic rehabilitation of the posterior edentulous maxilla is challenging due to inadequate bone volume resulting from alveolar ridge resorption and maxillary sinus pneumatization. This study explores the use of hyaluronic acid (HA) as a biomaterial in maxillary sinus elevation, particularly in combination with a fluid dynamic approach, as an alternative to traditional lateral approaches and granular biomaterials. Methods: A prospective study was conducted on 58 patients with posterior maxillary edentulism. Preoperative CBCT scans assessed residual bone height and sinus width. A minimally invasive surgical protocol utilizing a device for fluid-dynamic membrane elevation and injection of 2% cross-linked hyaluronic acid was employed, followed by simultaneous implant placement. Postoperative follow-up included a CBCT scan at 12 months to evaluate new bone height, measured mesially and distally. Implant stability was assessed using resonance frequency analysis at second-stage surgery. Results: A significant increase in bone height was observed at 12 months post-surgery, with an average bone gain of 7.5 mm. All 58 implants achieved primary stability, and no implant failures or signs of peri-implantitis were noted during the follow-up period. Higher bone gain was observed in wider sinuses. Conclusions: The fluid-dynamic transcrestal sinus floor elevation technique combined with hyaluronic acid appears to be a minimally invasive and effective method for achieving significant bone regeneration in the posterior maxilla, facilitating implant–prosthetic rehabilitation with potentially low risks and morbidity. Further large-scale studies are warranted to validate these findings across diverse clinical scenarios. Full article

Hyaluronic acid (HA) is a linear, unbranched polysaccharide classified as a glycosaminoglycan. While HA is found in various tissues throughout the body, over half of its total proportion is found in the skin. The role of HA in the skin is complex and multifaceted. HA maintains proper hydration, elasticity, and skin firmness, serving as a key extracellular matrix (ECM) component. With age, HA production gradually decreases, leading to reduced water-binding capacity, drier and less elastic skin, and the formation of wrinkles. Additionally, HA plays an active role in the wound-healing process at every stage. This review summarizes the current background knowledge about the role of HA in skin aging and wound healing. We discuss the latest applications of HA in aging prevention, including anti-aging formulations, nutricosmetics, microneedles, nanoparticles, HA-based fillers, and skin biostimulators. Furthermore, we explore various HA-based dressings used in wound treatment, such as hydrogels, sponges, membranes, and films. Full article

Human placental-derived allografts are biomaterials categorized as cellular, acellular, matrix-like products (CAMPs) that can serve as wound coverings due to placenta tissue’s innate barrier function. The placental membrane consists of three layers, the amnion, the intermediate layer (IL), and the chorion, each contributing distinct functional and biological properties. This study investigates how variations in layer composition influence the Extracellular Matrix (ECM) and growth factor profiles of placental allografts. We compared Dual Layer (amnion–amnion), Full Thickness (amnion–intermediate–chorion, FT), and a novel four-layer allograft configuration (amnion–intermediate–chorion–amnion, ACA). Histological analyses using hematoxylin and eosin (H&E) and Masson’s trichrome staining revealed distinct structural architecture among the three allografts, with FT and ACA exhibiting 4.9 times and 5.7 times greater thickness as compared with the Dual Layer, respectively. Compositional studies revealed different concentrations of key ECM components (collagen, elastin, proteoglycans, hyaluronic acid) and growth factors (ANG-2, EGF, PDGF-AA, VEGF) across allografts. The collagen concentration was two times higher in ACA as compared with the Dual Layer and FT. Additionally, FT and ACA demonstrated higher levels of growth factors and other ECM components, underscoring their biochemical diversity. These findings highlight the fact that the structural and biochemical properties of placental-derived allografts depend on their layer composition. This study underscores the importance of tailoring layer configurations that are optimized for clinical applications of CAMPs, enabling clinicians to select the most suitable grafts for clinical use, such as for wound management. Full article

Natural polysaccharides are biocompatible and biodegradable; therefore, they can be widely used in drug delivery, tissue engineering and wound healing. In this context, the interactions between polysaccharides, drugs and biological membranes are of great interest. In this paper, a 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayer was used as a model membrane to study the interactions with polysaccharides: chitosan (Ch) and/or hyaluronic acid (HA) and a nonsteroidal anti-inflammatory drug (NSAID) naproxen (NAP). The changes in the physicochemical properties of the model membrane were characterized by means of the Langmuir monolayer technique combined with Brewster angle microscopy (BAM). Compression/adsorption isotherms and morphology images were obtained at 20 °C. They allowed us to determine the effect of the subphase type (Ch, HA, Ch–HA) on the behavior of DPPC monolayers in the absence and presence of NAP, their elasticity, morphology and stability as a function of time. A potential mode of interactions between the phospholipid, polysaccharides and drug responsible for the change in membrane properties was proposed. These interactions regulate the efficiency of drug delivery systems, being of importance for living organisms in pain relief and wound healing. Full article

In regenerative periodontal treatment, barrier membranes restore periodontal support and aid tissue healing, but slow hard tissue regeneration can disrupt healing and cause tooth instability. This study aimed to fabricate a periodontal membrane through electrospinning poly(L-lactide-co-D, L-lactide) with varying β-tricalcium phosphate (β-TCP) percentages (0%, 10%, 30%, and 40%) treated with hyaluronic acid to enhance bone regeneration in alveolar bone defects. Their ability to promote biomimetic mineralization was characterized using field emission scanning electron microscopy (FESEM) analysis, wettability, and mechanical properties. Biocompatibility and osteogenic differentiation were evaluated by examining BMSCs’ behavior. In vivo, the PLA/β-TCP membrane’s potential to promote bone regeneration was assessed through CT imaging and histological examination. FESEM analysis revealed β-TCP agglomerations within PLA fibers, increasing tensile strength. Water contact angle measurements showed better wettability and higher cell viability after hyaluronic acid treatment, indicating non-cytotoxicity. Membranes with 10% and 30% (w/w) β-TCP significantly enhanced cellular activities, including proliferation and osteogenic differentiation. Animal tests showed a significant bone growth rate increase to 28.9% in the experimental group compared to 24.9% with the commercial product Epi-Guide after three months. Overall, PLA with 30% β-TCP optimally promoted periodontal hard tissue repair and potentially enhanced bone regeneration. Full article

Buccal drug delivery offers a promising alternative for avoiding gastrointestinal degradation and first-pass metabolism. However, enhancing the buccal epithelial barrier’s permeability remains challenging. This study explores the effects of ethanolic extracts from Citrus medica var. Balady (CM), Citrus medica var. Calabria (CMC), and Origanum dayi (ORD) on buccal epithelium permeability in vitro using a TR146 cell-based model. The cell viability assay revealed that the extracts were non-toxic at the concentration range tested (<0.5% w/v). Surprisingly, none of the tested extracts significantly enhanced the buccal permeability of 40 kDa Fluorescein Isothiocyanate Dextran (FD40). However, the CMC and ORD extracts significantly reduced the epithelial permeability of FD40, mirroring the effects of hyaluronic acid (HA), a known barrier integrity enhancer. The total phenolic content (TPC) analysis suggested a potential link between the phenolic concentration and epithelial barrier reinforcement. The rapid colorimetric response method was applied to assess the interaction of these extracts with biological membranes. The results indicated that HA interacts with cellular membranes via lipid bilayer penetration, whereas the extracts likely influence the barrier integrity through alternative mechanisms, such as ligand–receptor interactions or extracellular matrix modulation. These findings highlight the potential of CMC and ORD extracts as natural agents to enhance buccal epithelial integrity. In conclusion, incorporating these extracts into formulations, such as hydrogels, could offer a cost-effective and biocompatible alternative to HA for improving buccal cavity health. Full article

Gold nanoparticles (Au NPs) are a promising target for research due to their small size and the resulting plasmonic properties, which depend, among other things, on the chosen reducer. This is important because removing excess substrate from the reaction mixture is problematic. However, Au NPs are an excellent component of various materials, enriching them with their unique features. One example is hydrogels, which provide a good, easily modifiable base for multiple applications such as cosmetics. For this purpose, various compounds, including hyaluronic acid (HA) and its derivatives, are distinguished by their high water-binding capacity and many characteristics resulting from their natural origin in organisms, including biocompatibility, biodegradability, and tissue regeneration. In this work Au NPs were synthesized using a green chemistry method, either by using onion extract as a reductant or chemically reducing them with sodium citrate. A complete characterization of the nanoparticles was carried out using the following methods: Fourier-Transform Infrared Spectroscopy (FT-IR), Electrophoretic (ELS), and Dynamic Light Scattering (DLS) as well as Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM). Their antioxidant activity was also tested using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH). The results showed that the synthesized nanoparticles enrich the hydrogels with antioxidant properties and new surface properties (depending on the reducing agent, they can be more hydrophilic or hydrophobic). Preliminary observations indicated low cytotoxicity of the nanomaterials in both liquid form and as a hydrogel component, as well as their lack of penetration through pig skin. The cosmetic properties of hydrogel masks were also confirmed, such as increasing skin hydration. Full article

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity. Full article

Introduction: Globally, the health and quality of life of millions of people are negatively affected by diabetic foot ulcers (DFUs). To treat these chronic wounds, a novel injectable drug for closing DFUs composed of micronized amniotic membrane was developed. This new therapeutic drug for wound repair expands on traditional allograft therapies by allowing extracellular matrix proteins, growth factors, and cytokines to reach wound anatomies in DFUs that are difficult to treat. The aim of this study was to evaluate the components of the injectable drug. Methods: Liquid chromatography with tandem mass spectrometry and a Quantibody^® human cytokine array were conducted to identify and characterize growth factors and proteins known to contribute to wound healing. In addition, hyaluronic acid was quantified and compared between the injectable and human amniotic fluid using a hyaluronan enzyme-linked immunosorbent assay. Cell proliferation, migration, angiogenesis, and viability were evaluated to assess the performance of the novel injectable in vitro. The rheometric properties of the product were evaluated by assessing it pre- and post-injection through a 22-gauge needle to measure the viscosity using a shear- and temperature-dependent viscosity protocol. Results: Liquid chromatography with tandem mass spectrometry and Quantibody^® human cytokine array revealed growth factors and proteins imperative for wound healing. The quantified hyaluronic acid was compared between the injectable and human amniotic fluid, resulting in a statistically significant difference, with higher protein concentrations found in the injectable. In vitro qualitative and quantitative analysis confirmed an increase in cell viability, proliferation, and migration when treated with the drug. An evaluation of the rheometric properties of the injectable drug after passing through a 22-gauge cannula presented no alterations to the biologic drug. Conclusions: Collectively, these data present the potential of a novel injectable drug for the treatment of DFUs. Full article

The current study aimed to investigate the physicochemical properties of the natural eggshell membrane (NEM) and its protective effects against H₂O₂-induced oxidative stress in human chondrocytes (SW-1353). Bioactive components from NEM related to cartilage were profiled, consisting of 1.1 ± 0.07% hyaluronic acid, 1.2 ± 0.25% total sulfated glycosaminoglycans as chondroitin sulfate, 3.1 ± 0.33% collagen, and 54.4 ± 2.40% total protein. Protein was hydrolyzed up to 43.72 ± 0.76% using in vitro gastro–intestinal digestive enzymes. Peptides eluted at 9.58, 12.46, and 14.58 min using nano-LC-ESI-MS were identified as TEW, SWVE, and VYL peptides with an M/Z value of 435.1874, 520.2402, and 394.2336, respectively. Radical scavenging activity of NEM at 10 mg/mL using the ABTS assay was revealed to be 2.1 times higher than that of the positive control. NEM treatment significantly enhanced cellular SOD expression (p < 0.05). Pre-treatment with NEM (0.1, 1, and 10 mg/mL) dose-dependently reduced H₂O₂-induced ROS levels in SW-1353. Cell live imaging confirmed that NEM pre-treatment led to a significant reduction in apoptosis expression compared to control. Results from the present study suggest that NEM rich in cartilage protective components including hyaluronic acid, collagen, and chondroitin antioxidative peptides could be a potential therapeutic agent for osteoarthritis (OA) by scavenging oxidative stress. Full article

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer. Full article

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC₅₀ = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior. Full article