Biomedical subjects

V Hasirci

Publications and source records attributed to V Hasirci.

At least 37 records · Page 2Linked to original sources

PubMed2001

In vivo response to biodegradable controlled antibiotic release systems.

In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy- valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone and the Duocid-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid- and Sulperazone-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. Inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone-P(3-HB-co-4-HB) and Duocid-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis.

Animals↗

PubMed2000

Biodegradable foam coating of cortical allografts.

Clinical outcomes of bone allograft procedures may be improved by modifying the surface of the graft with an osteoconductive biopolymeric coating. In this comparative in vitro study, we evaluated the dimensional stability, mechanical strength, hydrophilicity, and water uptake of biodegradable foams of poly(propylene fumarate) (PPF) and poly(d,l-lactic-co glycolic acid) (PLGA) when applied as surface coatings to cortical bone. Cortical bone samples were divided into four groups: Type I, untreated bone; Type II, laser-perforated bone; Type III, partially demineralized bone; and Type IV, laser-perforated and partially demineralized bone. Results show that PPF wets easily, achieving 12.5% wt/wt in 30 min. Compressive tests on the PPF foam material showed that the compressive strength was 6.8 MPa prior to in vitro incubation but then gradually reduced to 1.9 MPa at 8 weeks. Push-out and pulloff strength tests showed that initially both PPF and PLGA foam coatings had comparable adherence strengths to the cortical bone samples (100-150 N). When additional geometrical surface alteration by perforation and demineralization of the bony substrate was employed, in vitro adherence of the PPF foam coating was further increased to 120 N, demonstrating a statistically significant improvement of push-out strength throughout the entire 8-week observation period (p<0.0002 for all four data points). The pore geometry of PPF-foam coatings changed little over the 2-month evaluation period. In comparison, PLGA foam coating around the cortical bone samples rapidly lost structure with a decrease of 67% in strength seen after 1-week in vitro incubation. These new types of bone allografts may be particularly useful where the use of other replacement materials is not feasible or practical.

Bone Remodeling↗

PubMed2000

Tissue responses to molecularly reinforced polylactide-co-glycolide implants.

Plates for internal fixation fabricated from biodegradable polymers degrade via an autocatalytic route. When they are used in bone implants of significant size and thickness, hollowing of the implant may occur while the overall dimensions appear unchanged. We hypothesized that incorporation of a cross-linked polypropylene fumarate matrix into polylactide-co-glycolide bone plates may provide an internal molecular network which prevents implant collapse. Cross-linking reagents of varying hydrophilicity including N-vinylpyrrolidone (VP), hydroxyethylmethacrylate (HEMA), and ethyleneglycol dimethacrylate (EGDMA) were employed. With the objective of determining the most biocompatible and structurally sound composition for molecular reinforcement, we investigated tissue responses in both subcutaneous and orthotopic rodent implantation models in relation to maintenance of implant integrity by histologic, histomorphometric, and stereomicroscopic analysis. Results showed that tissue responses were correlated with dimensional stability of the implants. The most favorable results were seen with the hydrophobic cross-linker EGDMA; this may have been related to the initial reduction of the water uptake by the implant. Cross-linking of polypropylene fumarate with EGDMA within a polylactide-co-glycolide bone plate may offer a means to maintain excellent biocompatibility while improving dimensional stability of biodegradable bone plates.

Animals↗

PubMed2000

High strength bioresorbable bone plates: preparation, mechanical properties and in vitro analysis.

Biodegradable bone plates were prepared as semi-interpenetrating networks (SIPN) of crosslinked polypropylene fumarate (PPF) within a host matrix of either poly(lactide-co-glycolide)-85:15 (PLGA) or poly(1-lactide-co-d,l-lactide)-70:30 (PLA) using N-vinylpyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (HEMA), and methyl methacrylate (MMA) as crosslinking agents. Hydroxyapatite (HAP), an inorganic filler material, was used to further augment mechanical strength. The control crosslinking agent (NVP) was replaced partially and totally with other crosslinking agents. The amount of crosslinking agent lost, the characterization change in the mechanical properties and the dimensional stability of the bone plates after in vitro treatment was calculated. The optimum crosslinking agent was selected on the basis of low in vitro release of NVP from SIPN matrix. Bone plates were then prepared using this crosslinking agent at 5 MPa pressure and at temperatures between 100-140 degrees C to determine if there was any augmentation of mechanical properties in the presence of the crosslinked network. In vitro analysis showed that 90% of the crosslinking agent was lost on plates using NVP as a crosslinking agent. This loss was reduced to 50% when NVP was partially replaced with EGDMA or MMA. EGDMA was determined to be superior because (1) its low release as a crosslinking agent, (2) flexural plate strength of 50-67 MPa, (3) flexural modulus of 7-13 GPa, and (4) manufacturability stiffness of 300-600 N/m. HAP-loading resulted in an additional increase in values of mechanical parameters. Substituting PLGA with PLA in the PPF-SIPN did not show any additional improvement of mechanical properties.

Absorbable Implants↗

PubMed1999

Sulbactam-cefoperazone polyhydroxybutyrate-co-hydroxyvalerate (PHBV) local antibiotic delivery system: in vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis.

In this study, a novel antibiotic carrier system for use in the treatment of implant-related and chronic osteomyelitis was developed. Sulbactam-cefoperazone was introduced to rods of polyhydroxybutyrate-co-hydroxyvalerate (22 mol % HV, w/w), a member of a family of microbial-origin polymer that is biodegradable, biocompatible, and osteoconductive due to its piezoelectric property. The antibiotic-loaded carrier was implanted into the infection site that was induced by Staphylococcus aureus inoculation into the rabbit tibia. The effectiveness of this was assessed macroscopically, radiographically, bacteriologically, and histopathologically. Findings of infection subsided on day 15 and almost complete remission was observed on day 30. The control side that contained antibiotic-free rods, however, worsened. These findings prompted us to conclude that the novel biodegradable antibiotic carrier developed in the present study seems to be a promising candidate for use in the treatment of severe bone infection.

Animals↗

PubMed1999

Antibiotic release from biodegradable PHBV microparticles.

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

Bacteria↗

PubMed1999

Development of a calcium phosphate-gelatin composite as a bone substitute and its use in drug release.

This study was carried out to develop a calcium phosphate-gelatin composite implant that would mimic the structure and function of bone for use in filling voids or gaps and to release bioactive compounds like drugs, growth hormones into the implant site to assist healing. XDS analysis of the synthesized calcium phosphate revealed a calcium to phosphorus molar ratio of ca. 2.30, implying a less erodible material than hydroxyapatite (1.67). Release of the antibiotic gentamicin from the implant was with a burst, whether in situ or in vivo, followed by an almost constant release for about three months. It was found that the release rate could be decreased by increasing the density of the gelatin membrane. Upon implantation into rabbit tibia the release duration was substantially shortened (to about 4 weeks) with respect to the in situ tests basically due to the degradation of gelatin. In vivo studies with rabbits confirmed this degradation. The composite was perfectly biocompatible as shown by the histological studies. It, thus, has a great potential as a bone substitute material.

Animals↗

PubMed1999

A novel osteochondral implant.

A novel implant for the use as an osteochondral graft was designed. This implant was prepared by stepwise formation of calcium phosphate crystals within the matrix of a lyophilised collagen sponge. Chondrocytes were then grown on this material to create the osteochondral implant. The implant was characterized with light microscopy, scanning electron microscopy (SEM), electron diffraction crystallography (EDX), and IR. It was observed with IR that the implant had a peak, that was not found so distinctly in its components, at 1400 cm(-1), implying a strong interaction of the two main ingredients of the implant, calcium phosphate and collagen. This strong interaction was also shown in the graft degradation test while the untreated collagen sponge degraded rapidly (in one day) the mineral loaded implant was able to maintain its integrity for two weeks. In the chondrocyte culture medium degradation of the implant was shown by a decrease of the calcium content and calcium to phosphorous ratio. Also, EDX revealed the presence of sulfur one and two weeks after incubation, an element not found among the components of the implant, possibly due to the development of an extracellular matrix. SEM showed that the form of the crystals of calcium phosphate differed depending on whether they were prepared on the template, collagen, or in the absence of a template. The chondrocytes appeared to be growing in number on the implant and their shapes were morphologically normal. The chondrocyte loaded collagen-calcium phosphate composite could thus be considered a potential tissue engineered osteochondral implant.

Biocompatible Materials↗

PubMed1998

An overview of the role of mineral solubility in silicosis and asbestosis.

Asbestosis and silicosis are fibrotic diseases initiated by the inhalation of silica-containing dusts, asbestos and quartz. There are various approaches for explaining the causes of these diseases. At present, our knowledge on the matter indicates that silicic acid dissolved from these minerals, contact between macrophages and minerals, highly reactive and oxidative species formed on the mineral surface, and lysosomal enzymes released upon engulfment of particulate mineral of appropriate size all contribute to various extents to the initiation of fibrosis. Among these mineral solubility seems to have a substantial contribution as a causative factor.

Asbestosis↗

PubMed1998

Synthesis and mechanical properties of interpenetrating networks of polyhydroxybutyrate-co-hydroxyvalerate and polyhydroxyethyl methacrylate.

Naturally occurring, biocompatible, and biodegradable polyhydroxybutyrate-co-hydroxyvalerate (PHBV), and synthetic, non-degrading polyhydroxyethylmethacrylate (PHEMA) membranes were prepared and their mechanical properties were studied. Their performances were compared with the interpenetrating networks (IPN) prepared by photopolymerization of HEMA in the presence of PHBV. The modulus of elasticity, failure stress and failure strain indicated that the IPNs are viscoelastic with properties closer to PHEMA but much stronger than PHEMA homopolymers. Incorporation of PHBV (7, 14 and 22% HV) affected the mechanical properties positively. Increasing the PHBV content increased the modulus of elasticity and failure stress nearly in all samples tested. PHBV (7, 14, and 22% HV, 300 mg) samples showed an approximately 17-30 fold increase in terms of modulus of elasticity and 7-10 fold increase in terms of failure stress. The scanning electron micrographs of the membranes showed that the PHEMA membranes are more porous than the PHBV membranes but the IPN structure displayed channels on the membrane surface indicating that HEMA polymerization was achieved by using the PHBV as a scaffold. With the use of the present technique, it is possible to synthesize supramolecular structures from molecules that are not compatible and miscible with each other.

Biocompatible Materials↗

PubMed1996

Imaging of liposomes by scanning tunneling microscopy.

In this study, unilamellar and multilamellar liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and dicetylphosphate were prepared. Scanning tunneling microscopy images of these liposomes on highly oriented pyrolytic graphite surfaces were obtained. It was observed that scanning tunnelling microscopy can be successfully used for high-resolution, three-dimensional structure analysis of liposomes under very mild conditions.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1995

Covalent immobilization of alpha-amylase onto pHEMA microspheres: preparation and application to fixed bed reactor.

Microspheres of poly(2-hydroxyethyl methacrylate) with and without cross-linker were prepared by suspension polymerization. As the amount of cross-linker increased, the equilibrium water content, enzyme loading, immobilization efficiency and recovered activity were all adversely affected. Enzyme alpha-amylase was immobilized onto the microspheres after activation with epichlorohydrin. The Km value for the immobilized enzyme (0.90% w/v) was much greater than that of the free enzyme (0.53% w/v). It was found that the inactivation constant (ki) increased from 2.23 x 10(-8) min-1 at 20 degrees C to 1.45 x 10(-4) min-1 at 60 degrees C. Since the enzyme activity increased as the temperature increased, the temperature profile yielded a peak at 50 degrees C. For free enzyme this is at 45 degrees C. The residence time was proportional to the percentage hydrolysis until a residence time of 12 min was reached. Beyond this the activity increase could not match the increase in residence time. The pH profile yielded a broadening upon immobilization in addition to a small shift to higher pH (from 5.5 to 6.0). The continuous run at 30 degrees C, 1.0% w/v starch concentration and flow rate of 40 cm3 h-1 led to only 20% loss in activity after a 120 h operation.

Biocompatible Materials↗

PubMed1993

Covalent immobilization of Aspergillus niger on pHEMA membrane: application to continuous flow reactors.

Poly(2-hydroxyethyl methacrylate) (pHEMA) membrane was prepared via photopolymerization and activated with epichlorohydrin. The conidia of Aspergillus niger strains (wild type 'NRRL-3' and genetically improved strain 'NRRL-3/2-2A') were covalently-immobilized on the membranes. Uniform growth of A. niger cells on membrane surfaces was verified by SEM. The glucose oxidase (GOD) activity of the immobilized cells was determined in a continuous flow membrane reactor (CFMR) by assaying for hydrogen peroxide produced. The activity was also determined in the culture fluids of A. niger strains, freely grown in batch cultures. The CFMR was run with 0.1 mol dm-3 glucose with a fixed flow rate of 20 cm3 h-1 for 60 h during which a 10% loss of the original activity was detected. The loss of the activity with the freely cultivated mycelia was about 50% after 30 h. The GOD activity of the improved strain NRRL-3/2-2A was about 20 times higher whether in immobilized or in free form. The GOD activity of the immobilized A. niger strains in the continuous flow membrane reactor was found to be 2.5 times better than their counterparts freely grown in batch cultures indicating that immobilization increases the activity and the stability of the microorganisms.

Aspergillus niger↗

PubMed1993

Immobilization of glucose oxidase: a comparison of entrapment and covalent bonding.

Glucose oxidase was immobilized onto poly(2-hydroxyethyl methacrylate) (pHEMA) membranes by two methods: by covalent bonding through epichlorohydrin and by entrapment between pHEMA membranes. The highest immobilization efficiency was found to be 17.4% and 93.7% for the covalent bonding and entrapment, respectively. The Km values were 5.9 mmol dm-3, 8.8 mmol dm-3 and 12.4 mmol dm-3 for free, bound and entrapped enzyme, respectively. The Vmax values were 0.071 mmol dm-3 min-1, 0.067 mmol dm-3 min-1 and 0.056 mmol dm-3 min-1 for free, bound and entrapped enzyme. When the medium was saturated with oxygen, Km was not significantly altered but Vmax was. The optimum pH values for the free, covalently-bound and entrapped enzyme were determined to be 5, 6, and 7, respectively. The optimum temperature was 30 degrees C for free or covalently-bound enzyme but 35 degrees C for entrapped enzyme. The deactivation constant for bound enzyme was determined as 1.7 x 10(-4) min-1 and 6.9 x 10(-4) min-1 for the entrapped enzyme.

Biotechnology↗

PubMed1993

Bioreactor applications of glucose oxidase covalently bonded on pHEMA membranes.

Glucose oxidase was immobilized onto poly(2-hydroxyethyl methacrylate) membranes by covalent bonding through epichlorohydrin. The highest immobilization efficiency was found to be 17.4%. The Km values were 5.9 and 8.8 mM for free and bound enzymes, respectively, and the Vmax values were 0.071 and 0.067 mM/min for free and bound enzymes. When the medium was saturated with oxygen Km was not altered significantly but Vmax was. The optimum pHs for the free and bound enzyme were determined to be 5 and 6, respectively, and the optimum temperature was 30 degrees C for both forms. The inactivation constant for the bound enzyme was found to be 1.7 x 10(-4) min-1.

Enzymes, Immobilized↗

PubMed1993

Glucose oxidase sandwiched between pHEMA layers: a continuous flow reactor application.

Glucose oxidase was entrapped between poly(2-hydroxyethyl methacrylate) membranes and conditions were optimized for high enzyme activity and high levels of entrapment. Highest entrapment was with a 78 microns thick coat. A continuous flow membrane reactor was designed and used. The reaction was first order with respect to glucose and to oxygen. Vmax values for the native and immobilized enzymes were 0.182 and 0.133 mM/min. The Km's for native and immobilized enzymes were 6.2 and 16.9 mM, respectively. At high substrate concentrations enzyme poisoning was detected. Both pH and temperature profiles moved to higher values upon immobilization. The enzyme retained 80% of its activity for at least 3 months in dry form.

Catalysis↗

PubMedDate not supplied

Vancomycin release from poly(D,L-lactide) and poly(lactide-co-glycolide) disks.

A biodegradable and biocompatible polymeric system was developed for the controlled release of vancomycin for the treatment of brain abscesses. Poly(D,L-lactic acid) (PLA) and its copolymers poly(lactide-co-glycolide) PLGA 90:10 and PLGA 70:30, were prepared. Polymer disks containing vancomycin (VN) were prepared by solvent casting from methylene chloride solutions. Degradation of the polymer disk was studied by scanning electron microscopy, NMR and GPC. SEM revealed an increasing degree of degradation with time with both PLGAs, the effect being more distinct in the PLGA with the higher glycolide content (PLGA 70:30), which was confirmed with GPC, which showed both a decrease in the molecular weights of PLGA and a decrease in the heterogeneity index (chain length distribution) upon incubation in isotonic phosphate buffer at 37 degrees C for up to 5 weeks. NMR showed a decrease in the CH2 contents of the copolymers, implying that the glycolide component of the copolymers is being preferentially degraded. In situ, vancomycin release behaviour of the disks in pH 7.4 phosphate buffer saline (PBS) was followed for approximately 2 months in a static system. It was observed that release was according to Higuchi kinetics (Q vs. t(1/2)), and introduction of low molecular weight PLA or hydrophilic compounds like PEG increased the release rate.

Algorithms↗

PubMedDate not supplied

In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) rods.

Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections. For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:cefoperazone or gentamicin, and their antibiotic release behaviours were studied under in vitro conditions in physiological phosphate buffer at room temperature. The release patterns were representative of release from monolithic devices where a rapid early release phase is followed by a slower and prolonged release. With PHBV 22 rods, the latter phase continued for approximately 2 months. This duration is critical because a proper antibiotic therapy of IRO requires the minimal effective concentration for at least 6 weeks. After in vitro release, voids with sharp edges were detected on the rods, indicating that the drug crystals dissolved but the polymer did not undergo erosion within this test period. Changing the polymer:drug ratio from 2:1 to 20:1 substantially decreased the drug release rate. A change of polymer type, however, did not lead to any detectable changes in the release patterns. Gentamicin release also followed a similar pattern, except that the concentration of the drug in the release medium exhibited a decrease after long release periods, indicating degradation (or decomposition) of the antibiotic in the release medium.

Absorbable Implants↗