1,721,072 research outputs found
Photosensitizer Loaded Contact Lenses As An Externally Stimulated Ophthalmic Drug Delivery System
Ophthalmic administration of drugs is primarily associated with the treatment of ocular diseases. 90% of the ophthalmic dosage forms are given topically. However, following the topical route, only 5% ocular bioavailability is achieved. The aim of my work is to address the problems associated with the conventional topical application. The present study investigated the preparation and characterization of Eosin Y (a model photosensitizer) liposomes loaded p-HEMA hydrogel films and its in vitro release profile triggered by an external stimulus (Argon Ion Laser). |A validated HPLC method was developed for quantification of Eosin Y in aqueous medium as per USP guidelines. The delivery system was prepared by dissolving Eosin Y loaded liposomes in the monomer solution (2-HEMA –EGDMA) using ammonium persulfate as the initiator of reaction for the formation of pHEMA hydrogel films. This delivery system showed 60% transmittance in the visible light region and 49% moisture content. In absence of laser, the in vitro release of free Eosin Y and Eosin Y loaded liposome from the hydrogel matrix were 24.3 ± 3.5% and 0.47 ± 0.1% respectively which were increased to 35.9 ± 6.8% and 0.79 ± 0.3% and 43.2 ± 19.4% and 1.0 ± 0.6% in presence of 5 and 10 minutes of Argon Ion laser (514nm) exposure, respectively.|The in vitro release data indicated that liposomal formulation was acting as a barrier to the release of drug in addition to the hydrogel matrix. The drug release can be triggered by an external laser stimulus whose exposure time can be manipulated to optimize the release profile. |This drug delivery device can benefit millions of people suffering from anterior eye diseases like dry eye, glaucoma (3.2 million of women of the United States suffer from dry eye, nearly 2.7 million Americans suffer from Glaucoma).ProQuest Traditional Publishing Optio
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The effects of SiO₂, ZnO, and MgO doping on the mechanical and biological properties of beta-tricalcium phosphate bioceramics for bone tissue engineering, in vitro and in vivo analysis
Beta-tricalcium phosphate ([Beta]TCP) is a promising bioresorbable ceramic for bone grafting applications that displays excellent biocompatibility because of its chemical similarity to natural bone. However, [Beta]TCP displays a relatively fast and uncontrolled dissolution rate, which leads to strength reduction over time - limiting its applications. One method of controlling the fast degradation rate, and subsequent strength loss, is through the introduction of metal oxide dopants. The objective of this research is to evaluate the influence of SiO2, ZnO, and MgO on the strength loss characteristics and biocompatibility of [Beta]TCP through in vitro and in vivo studies. Three doped compositions of [Beta]TCP were selected for in vitro analysis based on preliminary testing and literature review: i) [Beta]TCP + 0.5wt% SiO2, ii) [Beta]TCP + 0.5wt% SiO2+ 0.25wt% ZnO, iii) [Beta]TCP + 0.5wt% SiO2+ 0.25wt% ZnO + 1.0wt% MgO. From this study, a single composition, (ii), was selected for inclusion in a preliminary in vivo study. Dense ceramic samples were manufactured from phase pure [Beta]TCP nanocrystals, then characterized based on density, grain size, phase purity, and mechanical strength. In vitro testing subjected samples to 16 weeks in a simulated body fluid solution in order to test mechanical strength loss, weight change, dissolution, and bioactivity. In vivo samples were implanted for 16 weeks into the distal femur or lateral condyle of male Sprague-Dawley rats to assess tissue integration, implant degradation, and bone regeneration within the physiological environment. In vitro, all three dopant compositions affected the densification, grain size, and initial mechanical strength of [Beta]TCP. Additionally, compositions (ii) and (iii) exhibited decreased strength loss over time compared to [Beta]TCP - indicating that these compositions are promising candidates for select bone grafting applications. Consistent with published research, the in vivo implants displayed excellent biocompatibility as demonstrated by post-operative recovery of the animals. Both control and doped compositions showed signs of degradation, mechanical integration, and tissue in-growth at the implant-tissue interface. Compared to the control animals, the animals which received implants showed the highest blood serum concentrations of osteocalcin, sulfated glycosaminoglycans, and collagen
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Lithium-doped tricalcium phosphate and tricalcium phosphate/polycaprolactone particulate composite for bone-graft and drug-delivery applications
The first part of this study investigated the influence of Li-doping on the physical, mechanical and biological properties of b-Tricalcium phosphate (b-TCP) ceramic. b-TCP was synthesized with 0.22 mol % Li and 0.44 mol % Li using a wet coprecipitation method. A second set of samples was prepared by physically-mixing 0.10 mol% Li and 0.18 mol% Li with commercial b-TCP using a ball-milling method. In comparison to the undoped samples, the 0.44 mol% composition exhibited a decrease in compressive strength of 58.3 MPa, whereas the 0.22 mol% showed no statistically significant change. Compared to the undoped samples, the 0.10 mol% and 0.18 mol% samples showed a decrease of 63.6 and 50.9 MPa in compressive strength, respectively. Immunohistochemistry and MTT assay results showed an increase in the hFOB differentiation and proliferation activities with the addition of Li-dopant. Proliferation of hFOB cells from day 3 to day 7 showed an increase of 64% in the 0.22 mol% Li-TCP, compared to 30% in the undoped synthesized samples. Similarly, the physically-mixed samples showed an increase of 76% for the 0.10 mol% samples compared to 51% in the undoped commercial samples. The higher level of Li-doping decreased the proliferative activity in both groups, indicating that Li-doping is only beneficial at the lower concentrations. Immunohistochemistry and confocal microscopy results also showed that the levels of Li-doping in b-TCP can enhance the hFOB cellular differentiation compared to undoped b-TCP. Our results indicate that a low amount of Li-doping has the potential for applications in bone graft materials. The second part of this work investigated the effects of surface area, as well as surface composition on the loading and release behavior of bovine serum albumin (BSA). To begin, the BSA was adsorbed onto bare TCP powder of various surface areas, as well as onto a Tricalcium phosphate/polycaprolactone (TCP/PCL) particulate composite, which were constructed from the various bare TCP powders. It was concluded that surface area has a significant effect on the loading and release of BSA, whereby the amount of BSA adsorbed and released is increased as surface area is increased. It was also determined that PCL had no significant effect on the loading and release behavior of BS
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The effects of strontium-doped sol-gel and plasma-sprayed coatings on osteoblasts in static and dynamic culture conditions
An aging population, increased life expectancy and quality of life, and a rise in the number of younger, active patients requiring a metal implant has magnified the need for longer lasting implants. In order to test new materials, researchers must rely on static cell cultures or animal models, each have drawbacks to studying and confirming the efficacy of new implant materials. It is therefore the objective of this research are to modify the surface of Ti-6Al-4V ELI disks to enhance the bioactivity for implant applications in orthopedics and dentistry while improving the adhesion strength of bioceramic coatings. Additionally, it was the goal of this research to design and build a perfusion flow bioreactor, and demonstrate its use with an in vitro cell culture for use with future samples and cell lines. The hypothesis of the first aim is that the combination of TiNT with a sol-gel method of coating will increase the adhesion strength while improving bioactivity through the addition of strontium dopant. The hypothesis of the second aim is that the bioreactor will be able to accommodate different sample designs and culture cells as effectively as static cultures. In this study, titania nanotubes (Ti-NT) were grown on the surface of Ti64 ELI disks via anodic deposition, heat treated, and coated with pure hydroxyapatite (HA) and strontium-doped hydroxyapatite (Sr-HA) sol-gel coatings. In vivo results showed no significant difference between both plasma sprayed HA and Sr-HA and sol-gel coated HA and Sr-HA. Adhesion strength testing of the sol-gel coated samples showed that the HA coatings had strengths of 20.64 ± 2.37 MPa while Sr-HA exhibited 24.49 ± 10.99 MPa. The perfusion flow bioreactor was able to successfully culture osteoblast cells, with no significant difference between the reactor and static cell culture MTT data
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Titanium oxide nanotube and calcium phosphate on modified titanium surface for drug delivery
The objective of this study is to modify Titanium (Ti) surface with titanium oxide nanotube by anodization process and calcium phosphate by biomimetic and induction plasma spray to perform drug delivery. In the first part of the study anodization process was used to form titanium oxide nanotube followed by Hydroxyapatite coating and Gentamicin as an antibiotic drug delivery. Titanium is a bioinert material and, therefore, gets encapsulated after implantation into the living body by a fibrous tissue that isolates them from the surrounding tissues. In this work, titanium oxide layers were grown on commercially pure titanium substrate by anodization process using different electrolyte solutions namely (1) 1 v/v% HF, (2) 1.0 M H2SO4 with 0.1 M HF and (3) 0.25 wt% NH4F with ethylene glycol 10% DI water, (4) aqueous solution of 0.2 M citric acid, 0.1 M hydrofluoric acid and 1.0 M sulfuric acid. With 1 v/v% HF as an electrolyte the anodization process produced bioactive TiO2 films with a nanoporous structure at 20 V for 40 minutes. Cross-sectional view of the nanoporous surface reveals titanium oxide nanotubes of diameter 100 20 nm and length 400 100 nm. It was found that increasing anodization time Gentamicin was uploaded to the samples by applying the gentamicin aqueous solution followed by drying under vacuum infiltration. Drug release kinetics was studied and also Human osteoblast (HOB) cell attachment and growth behavior were studied using an osteoprecursor cell line (OPC 1) for 3, 7 and 11 days. In the second part of this study, radio frequency induction plasma spray was used to prepare HAp and doped HAp coatings on commercial pure titanium with improved crystallinity and phase purity. Hydroxyapatite plasma sprayed samples were loaded with 200 µg of alendronate sodium for each sample, and then the samples were coated with Polycaprolactone as a biodegradable polymer to reduce the drug release rate. These modified titanium surface implants have the potential to be used in load bearing application as well as drug delivery system in the term of a multifunctional device
Understanding the Effects of Dopants on Calcium Phosphate Ceramics: Bone Cell Differentiation and Bone Growth in vitro and in vivo
Thesis (Ph.D.), Program in Engineering Science, Washington State UniversityThe objective of this research is to further develop the understanding of trace elements in bone biology and, specifically, their potential osteogenic effects in calcium phosphate bone substitute ceramics. Trace elements including magnesium (Mg2+), silicon (Si4+), strontium (Sr2+) and zinc (Zn2+) were incorporated into β tricalcium phosphate (β -TCP) as dopants into various form factors including dense ceramic compacts, 3D printed scaffolds and porous scaffolds fabricated by an oil emulsion method. The hypothesis of this research is that the addition of these trace element dopants into β -TCP can significantly alter its phase stability, microstructure, mechanical strength and in vitro and in vivo biocompatibility.3D printed scaffolds containing 0.5% SiO2 and 0.25% ZnO increased the average density of pure TCP from 90.8 ± 0.8% to 94.1 ± 1.6% which resulted in an average 2.5 fold increase in compressive strength. Scaffolds that contained the smallest amount of designed porosity had compressive strengths of 5.48 ± 0.04 MPa and 10.21 ± 0.33 for pure and doped scaffolds, respectively. Doped samples demonstrated increased cellular proliferation. In vivo results in a murine model demonstrated that the presence of SiO2 and ZnO increased osteocalcin and collagen production as well as increased osteogenesis and angiogenesis over the course of 16 weeks.Further studies examining 1% SrO, 1%MgO, 0.5% SiO2 and 0.25% ZnO single dopant TCP systems on osteoblastic differentiation markers alkaline phosphatase (ALP) and runt related transcription factor 2 (Runx2) demonstrated the ability of dopants to increase cellular proliferation in the early stages of the osteoblastic lifecycle, while down regulating the Runx2 expression at later time points, allowing for faster terminal differentiation. SiO2 and ZnO dopants were also analyzed using quantitative polymerase chain reactions for the following targets in osteoblast cells: bone morphogenic protein 2 (BMP2), Runx2, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin. At day 21, all doped samples expressed 2-4 times less BMP2, 1.5-2.5 times greater OPG and 2-4 times less RANKL when compared to pure TCP. Mg and Sr doped samples expressed 2.5 times more Runx2, Si 1.5 times more and zinc similar amounts of Runx2 to pure TCP. These results demonstrate an affinity for the production of signaling molecules that favor increased osteoblastogenesis and decreased osteoclastogenesis.Program in Engineering Science, Washington State Universit
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Porous tricalcium phosphate scaffold for bone tissue regeneration
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Nanostructured hydroxyapatite and tricalcium phosphate based ceramics for bovine serum albumin protein delivery and bone implants using microwave sintering
The objective of this study was to investigate the potential of nanocrystalline hydroxyapatite [Ca10(PO4)6(OH)2, HA] and [beta]-tricalcium phosphate [[beta]-Ca3(PO4)2, [beta]-TCP] for controlled protein release and bone implant material. HA and [beta]-TCP nanopowders were synthesized using reverse micelle as template system. By varying synthesis parameters, [beta]-TCP nanopowders were synthesized with a particle size between 32 and 135 nm, different aspect ratios, and BET specific average surface area varying between 57 and 103 m2/g. Bovine serum albumin protein (BSA) release from [beta]-TCP and CDHA nanopowders was studied by ex situ adsorption of bovine serum albumin (BSA) onto nanoparticle surface. HA-BSA nanopowders were also synthesized by in situ co-precipitation technique. 2 mol% Zn2+ and Mg2+ were used as dopants to synthesize Zn2+ /Mg2+ doped HA-BSA nanopowders by in situ synthesis route. BSA release rate from ex situ synthesized [beta]-TCP-BSA nanopowders found to be faster compared to that from CDHA-BSA nanopowders. For in situ synthesized HA-BSA nanopowders, BSA release rate from Zn doped HA nanopowder found to be the highest, whereas much slower and sustained protein release was observed from in situ synthesized HA-BSA nanocarriers. Nanostructure HA compacts were processed using microwave sintering with ultrafine microstructures and improved mechanical properties for orthopedic implant applications. Nanostructured sintered HA compact showed superior compressive strength (395 36 MPa), indentation hardness (8.4 0.4 GPa) and indentation fracture toughness (2.0 0.1 MPa m1/2). HA compacts were assessed for cell material interaction using SEM, MTT assay and confocal microscopy after culturing human osteoblast cell line on HA disc surface for 1, 5 and 11 days. MTT assays showed higher number of living cell and faster proliferation on nano HA surface. Also osteoblast cells on nano HA surface expressed significantly higher amount of vinculin and alkaline phosphatase (ALP) protein markers for adhesion and differentiation respectively. This study showed that BSA release rate can be controlled by varying particle size, surface area, phase composition of HA and [beta]-TCP nanocarriers. Nanostructured HA exhibited superior mechanical strength and bioactivity com ared to micron grained HA compacts
Optimization of PZT based thin films and piezoelectric micromachined ultrasonic transducers (pMUTs)
Thesis (M.S.), Materials Science and Engineering, Washington State Universit
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Silver doped resorbable tricalcium phosphate ceramic scaffolds for bone grafts
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