Mixture Of Hyaluronic Acid Research Articles

Tuning the crosslinking and degradation of hyaluronic acid/gelatin hydrogels using hydrogen peroxide for muscle cell sheet fabrication.

Cell sheets have immense potential for medical and pharmaceutical applications including tissue regeneration, drug testing, and disease modelling. In this study, composite hydrogels were prepared from a mixture of phenolated hyaluronic acid (HA-Ph) and gelatin (Gelatin-Ph), with a controlled degree of polymer crosslinking and degradation, to fabricate muscle cell sheets from myoblasts. These hydrogels were obtained via hydrogen peroxide (H2O2)-mediated crosslinking catalysed by horseradish peroxidase (HRP) and peroxide-mediated cleavage of the polymer chains. The degrees of crosslinking and degradation were modulated by altering the exposure time to air containing H2O2. The results showed that exposing a solution of 2% w/v HA-Ph, 0.75% w/v Gelatin-Ph, and 1 unit mL-1 HRP to air with 16 ppm H2O2 for 60 min yielded a stiffer hydrogel (7.16 kPa Young's modulus) than exposure times of 15 min (0.46 kPa) and 120 min (3.98 kPa). Moreover, mouse myoblast C2C12 cells cultured on a stiff hydrogel and induced to undergo myogenic differentiation formed longer and higher-density myotubes than those on softer hydrogels. The cell sheets were readily detached within 5 min by immersing the HA-Ph/Gelatin-Ph hydrogels covered with a monolayer of cells in a medium containing hyaluronidase. Our findings demonstrate that composite hydrogels with properties tuned by controlling the exposure time to H2O2, show great promise as platforms for muscle cell sheet fabrication.

Protocolo “RichBlend” para preenchimento facial e bioestimulação de colágeno

ABSTRACT The “RichBlend” protocol was designed for facial filling and collagen biostimulation, by means of a mixture of calcium hydroxyapatite (CaHA), hyaluronic acid (AH) and autologous platelet concentrates. This work reports the case of a 53-year-old patient with cutaneous photoaging, loss of facial volume, multiple rhythms in the frontal and periorbital regions, also marked skin flaccidity, especially the eyelid. The treatment was done with botulinum toxin (65 U) and the “RichBlend” protocol. Venipuncture was performed and the blood was centrifuged to obtain i-PRF (injectable platelet-rich fibrin) and plasma gel. After venipuncture and blood centrifugation, i-PRF and plasma gel were obtained. CaHA (Radiesse®) was diluted: a) in saline solution + i-PRF (hyperdilution) for biostimulationof the lower third of the face; and b) in AH (Juvederm Ultraplus XC®) + plasma gel, for hydrolifting on the forehead and dark circles, malar and temples. Plasma gel was applied to the nasogenian grooves and then the entire face was properly massaged. The “RichBlend” protocol rejuvenated the patient, as it promoted filling, volumizing, collagen formation (biostimulation), reduction of flaccidity, in addition to skin whitening. Since HA and CaHA are high-cost products, their mixture with autologous platelet concentrates, in liquid or gel form, allows the use of a greater amount of filled and biostimulator material on the face, at a more affordable cost.

Interfacial engineering approaches to improve emulsion performance: Properties of oil droplets coated by mixed, multilayer, or conjugated lactoferrin-hyaluronic acid interfaces

This study investigated the effects of different interfacial structures on the performance of oil-in-water emulsions including their physicochemical stability, lipid digestion profiles, and nutraceutical bioaccessibilities. Emulsions containing oil droplets coated by lactoferrin (LF) and/or hyaluronic acid (HA) were prepared with different structural organizations: (i) LF only; (ii) LF + HA mixtures; (iii) LF + HA bilayers; and (iv) LF-HA covalent conjugates. The bilayers were formed by depositing HA onto LF-coated lipid droplets after homogenization, while the conjugates were formed by covalent attachment of HA to LF before homogenization. The interfacial pressure, adsorption kinetics, interfacial thickness, and surface load were characterized. The physicochemical properties and stability of the four types of emulsions were also measured and compared. The covalent attachment of HA to LF reduced the surface activity of the protein, which was attributed to a reduction in diffusion rate and surface hydrophobicity. The emulsifying activity and emulsion stability index of the LF were enhanced, and the salt stability and freeze-thaw stability of LF-stabilized emulsion were improved when HA was covalently attached to it. This effect was attributed to the formation of a relatively thick (161 nm) and strongly charged (−45.8 mV) interfacial layer that increased the steric and electrostatic repulsion between the oil droplets. Emulsions with mixed, bilayer, or conjugated LF-HA interfaces gave better photostability and bioaccessibility of two encapsulated nutraceuticals (curcumin and resveratrol) than LF interfaces. Overall, however, the LF-HA conjugates were the most effective at improving the performance of the emulsions. These results suggest that interfacial engineering technologies can be utilized to enhance the performance of emulsions.

New Materials Based on Molecular Interaction between Hyaluronic Acid and Bovine Albumin.

In this work, the interactions between hyaluronic acid and bovine serum albumin were investigated. The film-forming properties of the mixture were proven, and the mechanical and surface properties of the films were measured. The results showed the interactions between hyaluronic acid and albumin, mainly by hydrogen bonds. Molecular docking was used for the visualization of the interactions. The films obtained from the mixture of hyaluronic acid possessed different properties to films obtained from the single component. The addition of bovine serum albumin to hyaluronic acid led to a decrease in the mechanical properties, and to an increase in the surface roughness of the film. The new materials that have been obtained by blending can form a new group of materials for biomedicine and cosmetology.

Hybrid systems combining liposomes and entangled hyaluronic acid chains: Influence of liposome surface and drug encapsulation on the microstructure

Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid–polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.5% HA) at high liposome concentration (80 mM lipids). The objective was to elucidate the influence of liposome surface (neutral, cationic, anionic or anionic PEGylated), drug encapsulation and HA concentration in a buffer mimicking biological fluids (37 °C). First, liposomes were characterized by SANS, cryo-electron microscopy, and dynamic light scattering and HA by SANS, size exclusion chromatography, and rheology. Secondly, HA-liposome mixtures were studied by SANS. In HA, liposomes kept their integrity. Anionic and PEGylated liposomes were in close contact within dense clusters with an amorphous organization. The center-to-center distance between liposomes corresponded to twice their diameter. A depletion mechanism could explain these findings. Encapsulation of a corticoid did not modify this organization. Cationic liposomes formed less dense aggregates and were better dispersed due to their complexation with HA. Liposome surface governed the interactions and microstructure of these hybrid systems.

Constructing ultra-stable photothermal plastics assisted by carbon dots with photocaged reactivity

Constructing ultra-stable photothermal plastics assisted by carbon dots with photocaged reactivity

Rheological properties and decomposition rates of Gellan gum/hyaluronic acid/β-tricalcium phosphate mixtures

The effects of β-tricalcium phosphate (TCP) on the mixture of low acyl gellan gum (LA-GAGR) and hyaluronic acid (HA) were investigated for the rheological properties and decomposition rates. All the tested mixture samples exhibited shear-thinning and typical viscoelastic behaviors. The sample made with 1.0% TCP and 0.30% LA-GAGR had the highest viscosity and loss and storage moduli and displayed gel-like behavior with the highest swelling capacity. The same mixture also exhibited the lowest average cumulative decomposition rate. High concentrations of LA-GAGR and TCP increased the degree of cross-linking of the polysaccharides, and as a result, the mixture was more elastic and less fluidic and decomposed slower. The samples prepared by gradual mixing of LA-GAGR and TCP decomposed slower than the sample prepared by sudden mixing, which indicates the well-dispersed TCP enhanced cross-linking of the polymers. This study demonstrates the possible applicability of natural polysaccharide-based shear-thinning gels for biomedical applications.

Multifunctional thermo-sensitive hydrogel for modulating the microenvironment in Osteoarthritis by polarizing macrophages and scavenging RONS

Osteoarthritis (OA) is a common degenerative joint disease that can lead to disability. Blocking the complex malignant feedback loop system dominated by oxidative stress and pro-inflammatory factors is the key to treating OA. Here, we develop a multifunctional composite thermo-sensitive hydrogel (HPP@Cu gel), which is utilized by Poloxamer 407 (P407) and hyaluronic acid (HA) mixture as the gel matrix, then physically mixed with copper nanodots (Cu NDs) and platelet-rich plasma (PRP). Cu NDs is a novel nano-scavenger of reactive oxygen and nitrogen species (RONS) with efficient free radical scavenging activity. HPP@Cu gel is injected into the articular cavity, where it form an in situ gel that slowly released Cu NDs, HA, and PRP, prolonging the duration of drug action. Our results indicate that HPP@Cu gel could efficiently remove RONS from inflammatory sites and promote repolarization of macrophages to an anti-inflammatory phenotype. The HPP@Cu gel therapy dramatically reduces cartilage degradation and inflammatory factor production in OA rats. This study provides a reliable reference for the application of injectable hydrogels in inflammatory diseases associated with oxidative stress.Graphical

The Effect of Melatonin and Hyaluronic Acid Mixture on Hard Tissue Dimensional Changes Around Immediate Post-Extraction Implants.

The Effect of Melatonin and Hyaluronic Acid Mixture on Hard Tissue Dimensional Changes Around Immediate Post-Extraction Implants.

Antibacterial Activity of Chitooligosaccharides Derived from the Hydrolysis of Complex Consisting of Chitosan and Hyaluronic Acid

The complex of chitosan and hyaluronic acid was treated with enzyme to obtain chitosan oligosaccharide designated to COS hereafter. The degree of decomposition was confirmed by reducing sugar quantitative method, and the molecular weight size was confirmed by Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry analysis. Based on the fact that the substrate specificity of the enzyme is highly dependent on temperature, substrate concentration, and pH, etc, the COS obtained by treating a mixture of chitosan and hyaluronic acid, which physically mixes well, under the non-optimal reaction conditions of the chitosanase. Accordingly, it exhibited very significant antibacterial activity against Meticillin Resistant Stapylococcs aureus (MRSA). As a method for controlling molecular weight of COS, it was intended to propose a new enzyme usage as a study to identify the characteristics of the hydrolysates according to the reaction delay and enzyme activity through complex formation.

Novel Filler Technique: Hyaluronic acid and Calcium hydroxylapetite mixture resulting in favorable esthetic and longevity outcomes.

Novel Filler Technique: Hyaluronic acid and Calcium hydroxylapetite mixture resulting in favorable esthetic and longevity outcomes.

Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study

BackgroundThe study investigated whether allogeneic human umbilical cord blood-derived MSCs (hUCB-MSCs) could be safely used without treatment-related adverse events, reducing tunnel enlargement, and improve clinical results in human anterior cruciate ligament (ACL) reconstruction.MethodsThirty patients were enrolled consecutively. They were divided into three groups by randomization. In the negative control group, ACL reconstruction surgery without additional treatment was performed. In the experimental group, a hUCB-MSC and hyaluronic acid mixture was applied to the tendon-bone interface of the femoral tunnels during ACL reconstruction surgery. In the positive control group, only hyaluronic acid was applied. Finally, 27 patients were analyzed after the exclusion of three patients. The incidence of treatment-related adverse events, clinical outcomes, including second-look arthroscopic findings, and the amount of tunnel enlargement, were evaluated.ResultsThere were no treatment-related adverse events in the treatment groups. Tunnel enlargement in the experimental group (579.74 ± 389.85 mm3) was not significantly different from those in the negative (641.97 ± 455.84 mm3) and positive control (421.96 ± 274.83 mm3) groups (p = 0.6468). There were no significant differences between the groups in clinical outcomes such as KT-2000 measurement (p = 0.793), pivot shift test (p = 0.9245), International Knee Documentation Committee subjective score (p = 0.9195), Tegner activity level (p = 0.9927), and second-look arthroscopic findings (synovial coverage of the graft, p = 0.7984; condition of the graft, p = 0.8402).ConclusionsAllogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes.Trial registrationCRIS, Registration Number: KCT0000917. Registered on 12 November 2013; https://cris.nih.go.kr/cris/index.jsp

Hyaluronic Acid Accelerates VEGF and PDGF Release from Advance Platelet Rich Fibrin in Diabetic Foot Ulcer

BACKGROUND: Hyaluronic acid (HA) is an essential component of extracellular matrix and mediates signaling in wound healing. HA could induce growth factor release from Advanced Platelet Rich Fibrin (A-PRF), including Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF). However, concentrations of the released-VEGF and PDGF have not been clearly disclosed. Therefore, current study was conducted to measure the release of these growth factors in HA + A-PRF gel of diabetic foot ulcer (DFU) subjects.METHODS: Twenty DFU subjects were included in the study and treated with A-PRF or HA+A-PRF. A-PRF was derived from autologous peripheral blood and processed with low-speed centrifugation. HA was added with a ratio of 1:0.6. A-PRF or HA + A-PRF was applied topically on DFU. Upper tips of A-PRF or HA + A-PRF gels were collected on day 0, 3 and 7 for measurements of VEGF and PDGF concentrations with Enzyme-linked Immune-sorbent Assay (ELISA) methods.RESULTS: On day-3, both VEGF and PDGF concentrations of HA + A-PRF group were significantly higher than the VEGF (p=0.000) and PDGF (p=0.019) concentrations of A-PRF group. The VEGF and PDGF concentrations were continuously and significantly increased on day-7 of HA + A-PRF group, compared to the VEGF (p=0.000) and PDGF (p=0.004) concentrations of A-PRF group.CONCLUSION: Combination HA+A-PRF induces VEGF and PDGF release from A-PRF. A mixture of A-PRF and HA could be more effective than A-PRF alone for treatment of DFU.KEYWORDS: hyaluronic acid, advanced platelet rich fibrin, PRF, growth factor, VEGF, PDGF, diabetic foot ulcer

Hyaluronic acid-alendronate conjugate: A macromolecular drug delivery system for intra-articular treatment of osteoarthritis

ObjectiveOsteoarthritis (OA) is a painful degenerative disease of the whole joint structure, including articular cartilage, synovial fluid, and subchondral bone. Hyaluronic acid (HA), an anionic non-sulfated glycosaminoglycan, is commonly used for intra-articular (IA) treatment in OA, while bisphosphonates (BPs) are anti-resorptive drugs that act on the bone. Here, a novel conjugate with a covalent and hydrolysable linker between HA and alendronate (ALD) was designed as an attractive therapeutic strategy for IA drug delivery. DesignThe HA-ALD derivative was synthesized and tested in comparison with a simple mixture of HA and ALD for in vitro ALD release, rheological properties, cytotoxicity towards osteoblasts and chondrocytes and in an in vitro efficacy assay of OA inflammatory model on bovine cartilage explants. ResultsThe structure of HA-ALD was elucidated exhibiting no depolymerization and efficient drug incorporation. The controlled ALD release in vitro was slower compared to the simple mixture of HA and ALD; moreover, the derivative showed calcium-tuned rheological properties. The absence of cytotoxicity towards osteoblasts and chondrocytes was shown for up to 7 days, and the viability of chondrocytes was confirmed by fluorescence microscopy. Finally, a reduction in collagen release and MMP-13 expression was measured in the OA inflammatory model. ConclusionThis new HA-ALD derivative opens the door to a new approach for OA treatment, as it combines viscosupplementation and biological effects of HA with the pharmacological activity of BPs. Prolonged ALD release increased rheological properties and beneficial effect against cartilage degradation make it a promising IA therapy for OA.

Evaluation of Platelet Rich Fibrin Sandwiching technique with mixture of alloplastic bone graft and Hyaluronic Acid in repair of Recurrent Oronasal Fistula

Aim: is to evaluate efficacy of platelet rich fibrin (PRF) sandwiching technique associated with hyaluronic acid (HyA) mixed with alloplastic bone graft in closure of recurrent oronasal fistula after previously alveolar cleft grafting. Subjects and Methods: Our study conducted on 24 patients with recurrent unilateral oronasal fistula complaining of oronasal leakage. They were divided into two random equal groups. Group I, alveolar cleft defect was packed with alloplastic bone graft ( osteon II collagen) between two layers of PRF gel. While, in group II, alveolar cleft defect was packed with a mixture of alloplastic bone graft (osteon II collagen) and HyA between the two layers of PRF gel. All patients were observed clinically and radiographically (CBCT) for evaluation after three and six months postoperatively. Results: Our clinical results revealed that, all patients had uneventful wound healing except 4 cases in group I and one case in group II which had wound dehiscence and graft exposure at 1-week postoperatively. The radiographic results by CBCT scans showed a better new bone formation and good osseous union obliterating the oronasal defect.in group II than group I. There was a significant difference between bone density and bone resorption values in both groups at all intervals. Conclusion : Our results demonstrated that PRF sandwiching technique combined with a mixture of alloplastic bone graft and HyA could provide a favorable bony and soft tissue barriers for closure of recurrent oronasal fistula in alveolar cleft patients.

Synergistic Effects of Autologous Platelet-Rich Plasma and Hyaluronic Acid Injections on Facial Skin Rejuvenation.

Many therapeutic options are currently available for facial skin rejuvenation, but little evidence exists about the efficacy of combining such procedures. The aim of this study was to assess and investigate the synergistic effect of hyaluronic acid (HA) and autologous platelet-rich plasma (a-PRP) injections on facial skin rejuvenation. For this randomized controlled prospective study, 93 eligible patients were enrolled and randomized into 3 intervention groups to undergo a series of 3 treatment sessions with either a-PRP, HA, or a mixture of a-PRP and HA (Cellular Matrix; Regen Lab) injected into facial cheeks. A total of 93 patients were included. Treatment with Cellular Matrix led to a very significant improvement in the overall facial appearance compared with treatment with a-PRP or HA alone (P < 0.0001). Participants treated with Cellular Matrix showed a 20%, 24%, and 17% increase in FACE-Q score at 1, 3, and 6 months posttreatment, respectively. For the HA group, the improvement in FACE-Q score was 12%, 11%, and 6% at 1, 3, and 6 months posttreatment, respectively, whereas for the a-PRP group the improvement was 9%, 11%, and 8% at 1, 3, and 6 months posttreatment, respectively. Biophysical measurements showed significantly improved skin elasticity for the Cellular Matrix group compared with the groups receiving a-PRP or HA alone. No serious adverse events were reported. Combining a-PRP and HA seems to be a promising treatment for facial rejuvenation with a highly significant improvement in facial appearance and skin elasticity compared with a-PRP or HA alone.

Efficacy and safety of a cosmeceutical regimen based on a combination of low molecular weight hyaluronic acid, placental peptides and extract of Malus domestica in improving signs of periorbital skin aging

Background: Periorbital wrinkle formation is a relatively early sign of skin aging. The public interest in the reversal of aging has increased significantly among demanding patients and aesthetic practitioners within the past decades. However, many aesthetic patients, whether young or old, prefer to avoid invasive procedures wherever possible, seeking natural-looking results.Therefore, physicians have had to respond to their patient's expectations. Objectives: This study aimed to evaluate whether the synergistic anti-aging activity of MF3 Placenta 3R serum product has an influence towards the treating of wrinkles as well as skin hydration, and skin elasticity in the periorbital area. Methods: 23 healthy adult female volunteers were instructed to apply MF3 Placenta 3R serum containing a mixture of low molecular weight hyaluronic acid (LMWHA), placental peptides and extract of Malus domestica around the eye area twice daily during the study period of eight weeks. The skin measurements were performed in the periorbital area by investigating the skin elasticity (Cutometer) and skin hydration (Corneometer). Patients questionnaires were answered at 59 days. Results: The findings of the study proved a moisturizing impact of MF3 Placenta 3R serum throughout the trial that transformed into significant improvements in periocular skin hydration and elasticity. Conclusion: The tested formulation of MF3 Placenta 3R serum appears to be effective and may stimulate the periorbital skin rejuvenation in a women 44 – 52 years, resulting in the clinical appearance of smoother skin with less visible wrinkling. Further randomized, controlled studies have to be done to confirm these results.

Effect of Complex Coacervation with Hyaluronic Acid on Protein Transition in a Subcutaneous Injection Site Model System.

The occurrence of complex coacervation in an aqueous mixture of proteins (lysozyme, albumin, immunoglobulin G) and hyaluronic acid and its effect on protein transition in a model system was studied to elucidate factors determining the bioavailability of subcutaneously injected therapeutic proteins. Mixing of hyaluronic acid and the model proteins induced complex coacervation at solution pH close to or below the isoelectric point of the proteins. In vitro dialysis using membranes with large pore size tube represented a limitation in the protein transition of the coacervation mixture. Thermal analysis suggested there was retention of the protein conformation in the polymer complex.

Combined Treatment with Polynucleotides and Hyaluronic Acid Improves Tissue Repair in Experimental Colitis.

Inflammatory bowel diseases (IBDs) are chronic conditions that can benefit from the combined treatment of adenosine receptor agonists and hyaluronic acid (HA), which, binding the CD44, has pro-survival effects. Therefore, this study investigated the effects of a mixture of polynucleotides and HA in an experimental model of dinitrobenzenesulfonic acid (DNBS)-induced colitis. A group of 40 rats received a single intra-colonic instillation of DNBS, and after 6 h, animals were randomized to receive daily: (i) saline solution; (ii) polynucleotides (Poly; 8 mg/kg); (iii) polynucleotides (8 mg/kg) plus hyaluronic acid (HA; 15 mg/kg); and (iv) hyaluronic acid (HA; 15 mg/kg). Rats in the control group (n = 10) received saline solution only. Seven days after induction, animals receiving Poly plus HA showed reduced clinical signs, weight loss and colon shortening, ameliorated macroscopic and histological damage, and apoptosis. Moreover, the combined treatment reduced the positivity in the colonic infiltrate of CD3 positive T cells, CD20 positive B cells and CD44. Furthermore, Poly plus HA reduced colonic myeloperoxidase activity and malondialdehyde, indicating a dampening of the inflammatory infiltrate and oxidation products. Our research demonstrated that a combined treatment of polynucleotides with hyaluronic acid had a protective effect in a model of ulcerative colitis, suggesting that this association deserves further attention for the treatment of IBDs.

Treatment with Hyaluronic Acid and Collagen-Polyvinylpyrrolidone Improves Extracellular Matrix Assembly for Scarring after Tracheal Resection.

Treatment of tracheal stenosis is occasionally performed in combination with wound healing modulators to manipulate new extracellular matrix (ECM) formation and prevent fibrosis. Hyaluronic acid (HA) and collagen-polyvinylpyrrolidone (collagen-PVP) decrease fibrosis in experimental tracheal healing. However, they have not been used clinically as their effect on ECM components, which modify tracheal scarring, has not been described. Objective. To evaluate the effect of the application of HA, collagen-PVP, a mixture of HA and collagen-PVP (HA+collagen-PVP), and mitomycin C on the expression of decorin, matrix metalloproteinase 1 (MMP1), and MMP9, as well as the type of collagen and deposits formed in the scar after resection and end-to-end anastomosis (REEA) of the cervical trachea using an experimental model. Materials and Methods. Thirty dogs underwent REEA of the cervical trachea and were treated with different wound healing modulators: group I (n = 6), control; group II (n = 6), HA; group III (n = 6), collagen-PVP; group IV (n = 6), HA+collagen-PVP; and group V (n = 6), mitomycin C. The dogs were evaluated clinically and endoscopically for 4 weeks. Subsequently, macroscopic and microscopic changes, expression of ECM proteins, and collagen deposition in tracheal scars were analysed. Results. Groups II, III, and IV showed reduced endoscopic, macroscopic, and microscopic inflammation, improved neovascularization, high decorin expression (p < 0.01, analysis of variance (ANOVA)), and moderate expression of MMP1 (p < 0.003, ANOVA) and type I and III collagen (p < 0.05, Kruskal–Wallis). Groups IV and V developed fewer collagen deposits (p < 0.001, ANOVA). Conclusion. Treatment with HA and collagen-PVP improved post-REEA healing by increasing neovascularization, stimulating the expression of decorin, and regulating the expression of MMP1, as well as type I and III collagen and their deposition.