Addition Of HA Research Articles

Double printing of hyaluronic acid/poly(glycidol) hybrid hydrogels with poly(ε-caprolactone) for MSC chondrogenesis

This study investigates the use of allyl-functionalized poly(glycidol)s (P(AGE-co-G)) as a cytocompatible cross-linker for thiol-functionalized hyaluronic acid (HA-SH) and the optimization of this hybrid hydrogel as bioink for 3D bioprinting. The chemical cross-linking of gels with 10 wt.% overall polymer concentration was achieved by a UV-induced radical thiol-ene coupling between the thiol and allyl groups. The addition of unmodified high molecular weight HA (1.36 MDa) enabled the rheology to be tuned for extrusion-based bioprinting. The incorporation of additional HA resulted in hydrogels with a lower Young’s modulus and a higher swelling ratio, especially in the first 24 h, but a comparable equilibrium swelling for all gels after 24 h. Embedding of human and equine mesenchymal stem cells (MSCs) in the gels and subsequent in vitro culture showed promising chondrogenic differentiation after 21 d for cells from both origins. Moreover, cells could be printed with these gels, and embedded hMSCs showed good cell survival for at least 21 d in culture. To achieve mechanically stable and robust constructs for the envisioned application in articular cartilage, the formulations were adjusted for double printing with thermoplastic poly(ε-caprolactone) (PCL).

Impact of a timed-release FSH treatment from 2 to 6 months of age in bulls I: Endocrine and testicular development of beef bulls

In prepubertal males, FSH facilitates Sertoli cell proliferation and testis maturation. The study aimed to determine the effect of an exogenous FSH treatment on hormone secretion and testis development in Angus bulls. Bulls (n = 22) weaned at 53 ± 3.8 days of age were randomized into two treatment groups based on age and pedigree. Beginning at Day 59, bulls were injected im every 3.5 days with either 30 mg FSH (Folltropin-V; NIH-FSH-P1 units) in a 2% hyaluronan solution (FSH-HA, n = 11) or saline (control, n = 11) until Day 167.5. Blood samples to assess FSH, activin A, and testosterone were collected prior to each treatment. To determine how FSH profiles surrounding treatment were affected, three intensive blood sampling periods, each encompassing two treatment administrations, began at Day 66, 108, and 157, and blood was collected at 0, 6, 12, 18, 24, 36, 60, and 84 h respective to time of treatment. Scrotal circumference (SC) and BW were measured monthly. Bulls were castrated at Day 170 to measure testis size, seminiferous tubule diameter, and the number of Sertoli and germ cells per tubule cross-section. During intensive FSH sampling, FSH-HA bulls experienced an increase (P < 0.05) in FSH over control bulls for at least 18 h post-injection in all instances. In blood collected every 3.5 days, FSH concentrations in FSH-HA bulls were increased (P < 0.05) over initial Day 59 concentration from Day 97.5–167.5. FSH concentrations did not differ between treatments from Day 59–90.5, but were greater (P < 0.05) in FSH-HA from Day 94–167.5. Concentrations of activin A assessed for Day 59, 83.5, 94, 129, and 167.5 were greater (P < 0.05) in FSH-HA than control bulls on Day 83.5 and 94. The treatments did not differ (P > 0.1) in testosterone, BW, SC, testis size, tubule diameter, or number of germ cells per tubule. However, the number of Sertoli cells per tubule was greater in FSH-HA than control bulls (45.2 ± 1.4 vs. 41.6 ± 0.9 cells, P < 0.05). In summary, FSH-HA treatment every 3.5 days from Day 59–167.5 maintained elevated FSH for a minimum of 18 h post-injection, likely attributable to the addition of HA. We propose the exogenous FSH-HA treatment initiates a positive feedback loop that includes an increased density of Sertoli cells per tubule cross-section, which is related to increased activin A concentrations on Day 83.5 and 94. Furthermore, this activin A increase preceded an increase in endogenous FSH from Day 94–167.5 in FSH-HA bulls.

Fabrication of polylactic acid/hydroxyapatite/graphene oxide composite and their thermal stability, hydrophobic and mechanical properties

A series of polylactic acid/hydroxyapatite/graphene oxide composite (PLA/HA/GO) were fabricated via solution blending and casting method using N,N-dimethyl-formamide (DMF) and CH2Cl2 as mutual solvents. The physicochemical properties of the resulting composites were characterized by means of FT-IR, SEM, TEM, Raman spectra, XRD and N2-physisorption. Particularly, the thermal stabilities, hydrophobic and mechanical properties of PLA/HA/GO composites were systematically investigated. The influences of GO content on thermal stabilities, hydrophobic and mechanical properties of the composites were also evaluated. The results showed that the addition of GO and HA not only improved the thermal stability of PLA, but also improved the hydrophobic property of PLA-based composites. By compared with the PLA/HA/GO composite, the tensile strength of pristine PLA is slight high. The tensile strength and hardness of PLA/HA/GO composites increased with the increase of GO content. The obtained PLA/HA/GO composite may be a promising material for load-bearing orthopedic implants.

Nanoscale Silk-Hydroxyapatite Hydrogels for Injectable Bone Biomaterials.

Injectable hydrogel systems are important bone substitutes for regeneration because of their handling properties and the ability to fill irregular defects. Silk-hydroxyapatite composite materials with silk nanofibers in hydrogels were prepared and used as biomaterials for osteogenesis. These thixotropic silk nanofiber hydrogels and water-dispersible silk-HA nanoparticles were blended to form injectable nanoscale systems with a homogeneous distribution of a high HA content [60% (w/w)] to imitate bone niche. A modulus of ∼21 kPa was also achieved following the addition of HA in the systems, providing physical cues to induce osteodifferentiation. The composite hydrogels supported improved osteogenesis compared to that with silk nanofiber hydrogels. The newly formed bone tissue and bone defect healing were detected after implantation of the silk-HA composite hydrogels, suggesting utility for the regeneration of irregular bone defects.

Degradation of streptomycin in aquatic environment: kinetics, pathway, and antibacterial activity analysis.

Streptomycin used in human and veterinary medicine is released into the environment mainly through excretions. As such, its elimination in water should be investigated to control pollution. In this study, the degradation of streptomycin in water was studied, and the influence of variables, including light exposure, solution pH, temperature, ionic strength, dissolved organic matter (DOM), and coexisting surfactants, on degradation was investigated. Streptomycin degradation was consistent with the first-order model in aquatic environments. Its degradation rate under light exposure was 2.6-fold faster than that in the dark. Streptomycin was stable under neutral conditions, but it was easily decomposed in acidic and basic environments. Streptomycin degradation was enhanced by high temperature, and its half-life decreased from 103.4days at 15°C to 30.9days at 40°C. This process was also accelerated by the presence of Ca2+ and slightly improved by the addition of HA. Streptomycin degradation was suppressed by high levels of the cationic surfactant cetyltri- methylammonium bromide (CTAB), but was promoted by the anionic surfactant sodium dodecyl benzene sulfonate (SDBS). The main degradation intermediates/products were identified through liquid chromatography-mass spectrometry, and the possible degradation pathway was proposed. The antibacterial activity of streptomycin solution was also determined during degradation. Results showed that STR degradation generated intermediates/products with weaker antibacterial activity than the parent compound.

Processing and mechanical characteristics of magnesium-hydroxyapatite metal matrix biocomposites

Magnesium/hydroxyapatite composites were produced by conventional extrusion and their mechanical behavior studied under uniaxial compression at room temperature. The results evidence the capability of the HA for strengthening the Mg material, lowering its microstructural anisotropy and inhibiting deformation twinning. They also reveal that the ECAP processing is effective for improving the grain structure and reducing the crystallographic texture of these composites, giving rise to a significant enhancement of their yield strength and microhardness although the ultimate compressive stress worsens. The analysis of the strain hardening rate of the flow curves demonstrates that the HA addition and the ECAP processing are also effective in inhibiting non-basal dislocation slip.

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold.

Purpose: Statin is an effective factor for promoting osteogenesis. The aim of the present study was to evaluate the effect of simvastatin (SIM) and/or HA addition on changes in osteogenesis levels by human DPSCs transferred onto three-dimensional (3D) nanofibrous Poly (ε-caprolactone) (PCL)/Poly lactic acide (PLLA) polymeric scaffolds. Methods: For this purpose, a 3D nanofibrous composite scaffold of PCL/PLLA/HA was prepared by electrospinning method. SIM was added to scaffolds during DPSCs culturing step. Cell proliferation and osteogenic activity levels were assessed by using MTT assay and Alizarin Red assay methods. In addition, the expression of genes responsible for osteogenesis, including BMP2, Osteocalcin, DSPP and RUNX2, were determined before and 2 weeks after incorporation of SIM. Results: The MTT assay showed that PCL/PLLA/HA scaffolds seeded with DPSCs has significant (p<0.05) more proliferative effect than PCL/PLLA or DMEM cultured cells, additionally SIM administration improved this result over the PCL/PLLA/HA scaffolds without SIM treatment. SEM imaging revealed improved adhesion and probably osteogenic differentiation of DPSCs on PCL/PLLA/HA nanofibers treated with SIM, moreover the alizarin red assay ensured significant (p<0.05) higher mineralization of this group. Finally, real time PCR confirmed the positive regulation (P<0.05) of the expression of osteo/odontogenesis markers BMP2, Osteocalcin, DSPP and RUNX2 genes in PLLA-PCL-HA (0.1)-SIM group. Conclusion: As a result, addition of simvastatin with incorporation of hydroxyapatite in PCL-PLLA scaffolds might increase the expression of osteogenesis markers in the DPSCs, with a possible increase in cell differentiation and bone formation.

Poly(trimethylene carbonate) and nano‐hydroxyapatite porous scaffolds manufactured by stereolithography

Designing calcium phosphate‐loaded polymeric porous scaffolds with controlled architecture using stereolithography (SLA) has great potential in the field of bone tissue engineering. However, the use of poly(ester)s with suboptimal degradation property has mainly been reported. In the present work, we introduced a poly(trimethylene carbonate) (PTMC) and nano‐hydroxyapatite (HA) resin suitable for SLA manufacturing and created cytocompatible 3D porous structure. First, the resin formulation and HA content were optimized for photo‐crosslink‐based SLA fabrication process. Subsequently, we evaluated the influence of the resin composition on physico‐chemical characteristics of fabricated films and scaffolds. Then, the influence of the biomaterial composition on human bone marrow mesenchymal stem cell viability, adhesion and proliferation was assessed. Films and macroporous scaffolds were successfully produced by photo‐crosslinking with up to 40 wt% of HA (relative to PTMC). We demonstrated that addition of HA in PTMC matrices induced a direct effect on the surface properties, in terms of wettability and topography. Additionally, mechanical tests revealed a correlation between the amounts of HA loaded in PTMC and the stiffness of the SLA‐fabricated scaffolds. Importantly, the different photo‐crosslinked biomaterials exhibited in vitro cytocompatibility, similar to tissue culture polystyrene. Those data suggest the possibility to fabricate highly tunable HA‐loaded PTMC 3D porous structures for bone tissue engineering application. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Dual-Polymer Drops, Contact Lens Comfort, and Lid Wiper Epitheliopathy.

ABSTRACTPurposeThis study compared a new contact lens rewetting drop containing both carboxymethylcellulose and hyaluronic acid (CMC-HA) with a standard drop containing carboxymethylcellulose only (CMC). Symptoms of discomfort typical in lens wear and lid wiper epitheliopathy (LWE) were assessed over a 3-month period in a diverse sample of contact lens wearers.MethodsAdapted daily-wear contact lens subjects using hydrogel, silicone hydrogel, or rigid gas permeable lenses were enrolled in this prospective, randomized, double-masked, parallel-group, 90-day study conducted at 15 clinical sites. Subjects were randomized 2:1 to CMC-HA (n = 244) or CMC alone (n = 121) with dosage at least four times per day, along with their habitual lens care system. At baseline and at days 7, 30, 60, and 90, subject-completed questionnaires, bulbar conjunctival staining, LWE, contact lens distance visual acuity (CLDVA), and standard safety measures were assessed.ResultsAt day 90, CMC-HA performed significantly better than CMC in ocular symptoms including dryness throughout the day (p = 0.006), and burning/stinging throughout the day (p = 0.02) and at the end of the day (p < 0.001). CMC-HA also performed numerically better for dryness at the end of day (p = 0.06). LWE staining was improved in the CMC-HA group at day 90 whereas it increased slightly in the CMC alone group, with a significant between-group difference (p = 0.009). CMC-HA also demonstrated greater reduction in conjunctival staining compared with CMC alone at day 90 (p = 0.08). No differences in CLDVA, contact lens wear time, acceptability, and product use were observed, and safety outcomes were similar between groups.ConclusionsThe addition of HA to a standard CMC rewetting drop improves clinical performance. In this comparison of rewetting drop efficacy in contact lens wearers, LWE was a useful clinical sign for differentiating clinical performance.

Identification of photoproducts of fungicide cyprodinil and elucidation of transformation mechanism in water using LC-IT-TOF-MS/MS technique

This study aimed at investigating photodegradation of cyprodinil in aquatic solution under the simulated natural light or UV–visible irradiation (290–800 nm) using LC-MS/MS techniques. Effects of pH, nitrate ion, Fe (III), humic acid and TiO2 on photolysis kinetics of cyprodinil were explored. The photodegradation followed first-order reaction kinetics, and linear accelerating effects of Fe (III), nitrate ion and TiO2 with concentrations ranging from 0.1 to 5.0 mg L−1 on photodegradation were remarkably observed. HA at low concentration ranges (<3.0 mg L−1) enhanced cyprodinil photodegradation while the photocatalytic rate was weakened with more addition of HA. The degradation rate in alkaline solutions was greater than in acidic solutions. Six main transformation products (TPs) were separated and identified based on mass spectra data and density functional theory (DFT) quantum calculations, and their kinetic evolutions were also investigated. Ultimately, a tentative transformation mechanism was proposed based the identified TPs and their kinetic evolutions. The results indicated that one α-H on pyridine ring of cyprodinil was hydroxylated to form TPs 1. TPs 1 underwent a series of photochemical reactions involving ring-opening, addition of one H2O molecule and demethylation on three-member ring to form TPs 2, which was further hydroxylated on benzene ring to form TPs 6. TPs 3–5 were three isomers from Hofmann-Martius rearrangement of cyprodinil. These findings were of utmost importance for elucidating environmental fate of cyprodinil in aquatic ecosystem and further environmental risk evaluation.

Rapidly sintering of interconnected porous Ti-HA biocomposite with high strength and enhanced bioactivity

In this work, interconnected porous Ti-HA biocomposites with enhanced bioactivity, high porosity and compressive strength were prepared by spark plasma sintering (SPS) and space holder method. Pore characteristics, mechanical properties, corrosion behaviors and in vitro bioactivity of the porous Ti-HA were investigated. Results showed that porous Ti-HA with 5–30wt% HA contents possessed not only low elastic modulus of 8.2–15.8GPa (close to that of human bone) but also high compressive strength (86–388MPa). Although the HA partially decomposed and formed secondary phases, the sintered porous Ti-HA can still be good bioactivity. The homogeneity and the thickness of apatite layer increased significantly with the increase of HA. But with the thickness of apatite layer increased, micro-cracks appeared on the surface of porous Ti-30%HA. A model was built to discuss the current distribution and sintering mechanism of HA on Ti matrix during SPS process. It indicated that the excessive addition of HA would deteriorate the sintering quality, thus decreasing the mechanical properties and corrosion resistance. However, the combination of interconnected pore characteristics, low elastic modulus, high compressive strength and enhanced bioactivity might make porous Ti-HA biocomposites prepared by SPS a promising candidate for hard tissue implants.

Chondrogenesis of mesenchymal stem cells in a novel hyaluronate-collagen-tricalcium phosphate scaffolds for knee repair

Scaffolds are expected to play a key role in the induction of chondrogenesis of mesenchymal stem cells (MSCs) for cartilage tissue regeneration. Here, we report the development of a novel tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffold that can function as a stem cell carrier to induce chondrogenesis and promote cartilage repair, and the investigation of chondroinductive properties of scaffolds containing varying amounts of TCP, COL and HA. TCP-COL-HA scaffolds, as well as TCP-COL scaffolds at two different TCP/COL ratios (50:50 and 25:75), were evaluated for their ability to induce cartilage regeneration from rabbit mesenchymal stem cells (rMSCs) in vitro and in vivo. Chondrogenic differentiation was evaluated by sulphated glycosaminoglycan quantification, collagen type II immunohistochemistry, and qRT-PCR. Mechanical strength was evaluated by the compression test. The results showed that the TCP-COL-HA scaffolds enhanced rMSC chondrogenesis to a greater degree than did the TCP-COL scaffolds; for the latter, the scaffold with the lower TCP/COL ratio (25:75) was superior in terms of promoting rMSC chondrogenesis. Similar results were obtained in an ectopic implantation model in nude mice. In a critical-size rabbit osteochondral defect-repair model, rMSCs seeded on TCP-COL-HA scaffolds showed greater cartilage regeneration and integration into surrounding tissue than the TCP-COL groups, in which cartilage repair was more efficient at the 25:75 than at the 50:50 ratio. These results indicate that the addition of HA and different TCP/COL ratios can affect the chondroinductive capacity of scaffolds, and suggest that the TCP-COL-HA scaffold can serve as an effective cell carrier for cartilage regeneration.

Enhancement of Fenton oxidation for removing organic matter from hypersaline solution by accelerating ferric system with hydroxylamine hydrochloride and benzoquinone

Fenton oxidation is generally inhibited in the presence of a high concentration of chloride ions. This study investigated the feasibility of using benzoquinone (BQ) and hydroxylamine hydrochloride (HA) as Fenton enhancers for the removal of glycerin from saline water under ambient temperature by accelerating the ferric system. It was found that organics removal was not obviously affected by chloride ions of low concentration (less than 0.1mol/L), while the mineralization rate was strongly inhibited in the presence of a large amount of chloride ions. In addition, ferric hydrolysis–precipitation was significantly alleviated in the presence of HA and BQ, and HA was more effective in reducing ferric ions into ferrous ions than HA, while the H2O2 decomposition rate was higher in the BQ-Fenton system. Electron spin resonance analysis revealed that OH production was reduced in high salinity conditions, while it was enhanced after the addition of HA and BQ (especially HA). This study provided a possible solution to control and alleviate the inhibitory effect of chloride ions on the Fenton process for organics removal.

156. Cationic Lipopolymers for BCR-ABL siRNA Delivery and Growth Arrest in Chronic Myeloid Leukemia Tumors

Chronic Myeloid Leukemia (CML) is a disease initiated by hematopoietic stem cells after chromosomal translocation, which results in a BCR-ABL fusion oncogene. This fusion causes permanent activation of ABL tyrosine kinase that leads to myeloid cell expansion and accumulation of immature blast in bone marrow and bloodstream[1]. The shortcomings of current leukemia treatments i.e., acquired drug resistance and drug insensitivity, call for development of new treatments [2]. To this end, we have designed a carrier system using cationic lipo-polymers and evaluated the potential of siRNA therapy in vitro and in vivo using this polymer system. Cationic lipo-polymers were prepared by grafting aliphatic lipids (palmitic acid, PA, α-linoleic acid, αLA and carboxyl end-capped αLA) onto 1.2 kDa polyethyleneimine (PEI) via N-acylation [3]. The carboxyl-end capped αLA (tαLA) was prepared by coupling αLA with mercaptopropionic acid through thio-ester linkage. Structuralfunctionalities of tαLA and modified PEIs were analyzed through 1H-NMR spectroscopy and TNBS assay. GFP-expressing CML cells (GFP-K562 cells) were used as cell model and siRNA specific to BCR-ABL as therapeutic model. To create polymer/siRNA complexes that are more conducive for dissociation, polyanionic additive (hyaluronic acid, HA) was incorporated along with siRNA to PEI- tαLA complexes.GFP silencing efficacy of PEI in GFP-K562 cells was significantly increased (~ 60%) by hydrophobic modification and it was higher/or comparable to commercial agents, e.g. Lipofectamine™ 2000, Turbofect™ and PEI25. Addition of HA into complexes further increased the GFP silencing efficacy (~ 80%). A significant cell growth arrest was observed in day-6 and day-9 in GFP-K562 cells compared to control groups after the treatment with PEI1.2-αLA/BCR-ABL complexes. To evaluate the in vivo therapeutic efficacy, five-week old female nu-nu mice (Taconic Farms) were employed as animal models. Subcutaneous treatment (vicinity of the tumor) with PEI1.2-αLA/BCR-ABL was substantially effective in reducing tumor volumes starting from day 3 (Figure 1). ddPCR supports this silencing effect by revealing a reduction in BCR-ABL mRNA expression. Similar results were found when tumors were injected with siRNA intra-peritoneally. These preliminary results demonstrate the use of hydrophobically modified small molecular weight PEIs as effective carriers for siRNA delivery and therefore their potential for therapeutic use in the treatment of CML. View Large Image | Download PowerPoint Slide

Free Radical Production Is Increased During Hyperoxia And Exacerbated By Hypercapnic Acidosis (HA) In CO 2 ‐Chemosensitive Caudal Solitary Complex (cSC) Neurons In Rat Medullary Slices

CNS O2 toxicity (CNS-OT) seizures are the limiting factor when breathing hyperbaric O2 in diving & submarine medicine. O2-induced seizures are the result of oxidative and nitrosative stress that lead to CNS hyperexcitability. The risk for CNS-OT increases during CO2 retention. The cSC is an important cardiorespiratory integrative center that is stimulated during both HA & hyperoxia. The stimulatory effects of O2 & CO2 on cellular excitability suggests these molecules modulate one another in the CNS-OT mechanism. We have tested the following hypotheses in rat brain slices: 1) hyperoxia (95%O2) increases the production of reactive O2 & N2 species (RO/NS) in cSC cells (control O2, 40%), and 2) addition of HA exacerbates the rate of RO/NS production. We also investigated the effects of CO2-anesthesia on RO/NS production during subsequent administration of HA & hyperoxia. Fluorescence microscopy was used to measure the production rates of superoxide (˙O2-), nitric oxide (˙NO), and an aggregate pool of RO/NS (ONOO-, ˙NO2,˙CO3-) as the slope of fluorescence intensity (ΔFI/min). Results show the ΔFI/min of ⋅O2- and ⋅NO increased during hyperoxia, but were only seen in the presence of NOS and SOD inhibitors or SOD mimetics, respectively. Addition of HA increased the ΔFI/min of the aggregate pool, but only during hyperoxia. The effects of HA during hyperoxia are greater when CO2 anesthesia is not used prior to tissue harvesting. We conclude that 1) hyperoxia produces an enhanced redox and nitrosative environment for cSC neurons, 2) HA exacerbates downstream RO/NS production in an O2-dependent manner, and 3) use of CO2 anesthesia before euthanasia may blunt the effects of HA. ONR

Cerebral Angiographic Findings of Cosmetic Facial Filler-related Ophthalmic and Retinal Artery Occlusion.

Cosmetic facial filler-related ophthalmic artery occlusion is rare but is a devastating complication, while the exact pathophysiology is still elusive. Cerebral angiography provides more detailed information on blood flow of ophthalmic artery as well as surrounding orbital area which cannot be covered by fundus fluorescein angiography. This study aimed to evaluate cerebral angiographic features of cosmetic facial filler-related ophthalmic artery occlusion patients. We retrospectively reviewed cerebral angiography of 7 patients (4 hyaluronic acid [HA] and 3 autologous fat-injected cases) showing ophthalmic artery and its branches occlusion after cosmetic facial filler injections, and underwent intra-arterial thrombolysis. On selective ophthalmic artery angiograms, all fat-injected patients showed a large filling defect on the proximal ophthalmic artery, whereas the HA-injected patients showed occlusion of the distal branches of the ophthalmic artery. Three HA-injected patients revealed diminished distal runoff of the internal maxillary and facial arteries, which clinically corresponded with skin necrosis. However, all fat-injected patients and one HA-injected patient who were immediately treated with subcutaneous hyaluronidase injection showed preserved distal runoff of the internal maxillary and facial arteries and mild skin problems. The size difference between injected materials seems to be associated with different angiographic findings. Autologous fat is more prone to obstruct proximal part of ophthalmic artery, whereas HA obstructs distal branches. In addition, hydrophilic and volume-expansion property of HA might exacerbate blood flow on injected area, which is also related to skin necrosis. Intra-arterial thrombolysis has a limited role in reconstituting blood flow or regaining vision in cosmetic facial filler-associated ophthalmic artery occlusions.

Development of porous polyurethane/strontium-substituted hydroxyapatite composites for bone regeneration.

Polyurethane (PU) has been widely used for the biomedical applications but its potential for bone regeneration is limited due to its lack of osteoconductive properties. Strontium substituted hydroxyapatite (SrHA) particles, on the other hand, are known to exhibit a positive effect on bone formation. Therefore, the aim of this study was to (i) develop porous polyurethane scaffolds containing strontium SrHA nanoparticles (PU/SrHA) and (ii) compare their in vitro biological performance for applications in bone regeneration to PU scaffolds. SrHA and HA was synthesized using a conventional wet-chemical neutralization reaction at temperatures of 25, 50, and 80°C. Chemical analysis was performed by inductively coupled plasma-optical emission spectrometry. Synthesizing temperatures at 25 and at 50°C were selected for the composite preparation (abbreviated as HA-25, SrHA-25, HA-50, and SrHA-50, respectively). PU was synthesized from isophorone diisocyanate, polytetramethylene ether glycol, and 1,4-butanediol. Composite scaffolds were prepared by addition of HA or SrHA nanoparticles into PU scaffolds during polymer preparation. The results showed that the Sr content in HA nanoparticles increased with increasing synthesis temperature. The addition of nanoparticles decreased the elongation-at-break and tensile strength, but significantly increased the surface wettability of the PU scaffolds. In vitro degradation tests demonstrated that release of cations was significantly higher from PU/SrHA-50 composite scaffolds. Cell culture tests indicated that PU composites containing either HA or SrHA nanoparticles increased proliferation of bone marrow stem cells as compared to plain PU scaffolds, whereas osteogenic differentiation was not affected by the incorporation of HA nanoparticles irrespective of the incorporation of Sr.

Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors.

BackgroundHistamine (HA) regulates the sleep-wake cycle, synaptic plasticity and memory in adult mammals. Dopaminergic specification in the embryonic ventral midbrain (VM) coincides with increased HA brain levels. To study the effect of HA receptor stimulation on dopamine neuron generation, we administered HA to dopamine progenitors, both in vitro and in vivo.ResultsCultured embryonic day 12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors H1R, H2R and H3R. These undifferentiated progenitors increased intracellular calcium upon HA addition. In HA-treated cultures, dopamine neurons significantly decreased after activation of H1R. We performed intrauterine injections in the developing VM to investigate HA effects in vivo. HA administration to E12 rat embryos notably reduced VM Tyrosine Hydroxylase (TH) staining 2 days later, without affecting GABA neurons in the midbrain, or serotonin neurons in the mid-hindbrain boundary. qRT-PCR and Western blot analyses confirmed that several markers important for the generation and maintenance of dopaminergic lineage such as TH, Lmx1a and Lmx1b were significantly diminished. To identify the cell type susceptible to HA action, we injected embryos of different developmental stages, and found that neural progenitors (E10 and E12) were responsive, whereas differentiated dopaminergic neurons (E14 and E16) were not susceptible to HA actions. Proliferation was significantly diminished, whereas neuronal death was not increased in the VM after HA administration. We injected H1R or H2R antagonists to identify the receptor responsible for the detrimental effect of HA on dopaminergic lineage and found that activation of H1R was required.ConclusionThese results reveal a novel action of HA affecting dopaminergic lineage during VM development.

Preparation and Characterization of Organically Modified Montmorillonite-Filled High Density Polyethylene/Hydroxyapatite Nanocomposites for Biomedical Applications

The study investigated the introduction of organically modified montmorillonite (MMT) in high density polyethylene/hydroxyapatite (HDPE/HA) composites for biomedical applications. The addition of HA and MMT increased the strength and stiffness of HDPE/HA composites with deterioration in impact strength and elongation at break values. XRD and TEM analysis provided evidence of exfoliated MMT layers in HDPE/HA composites and the MMT layers remained exfoliated even with further addition of HA. Simulated body fluid (SBF) analysis revealed that the size of apatite layer increased with increasing immersion time and the formation of apatite layers on the surface of composites indicates excellent biocompatibility properties.

Comparing the Effects of a Biosurfactant and a Humic Acid on Arsenic Mobilization from Mine Tailings

AbstractBatch experiments were carried out to investigate the effects of a rhamnolipid biosurfactant (JBR425) and a humic acid (Fluka HA) on arsenic mobilization from a Cu-Zn mine tailings sample collected from Val d’Or, QC, Canada. When pH was below 7, the addition of HA at a low mass ratio (below 2.0 mg HA/g mine tailings) inhibited the mobilization of arsenic significantly. Arsenic mobilization increased with the mass ratio of added HA to the mine tailings. Especially under basic conditions, the introduction of HA significantly enhanced arsenic mobilization. Rhamnolipids were more efficient than HA at enhancing arsenic mobilization when pH was above 7. At a mass ratio of 10 mg/g and pH 11, arsenic mobilization reached 10 mg/kg by HA and 14 mg/kg by rhamnolipids, respectively. Capillary electrophoresis analyses indicated that arsenic oxidation-reduction and methylation reactions might not be a significant mechanism that was involved in arsenic mobilization by the HA and rhamnolipids. It was found tha...